Adjuvant Hepatic Arterial Infusion Research Articles

Imaging-based surrogate classification for risk stratification of hepatocellular carcinoma with microvascular invasion to adjuvant hepatic arterial infusion chemotherapy: a multicenter retrospective study.

Patients with microvascular invasion (MVI)-positive hepatocellular carcinoma (HCC) have shown promising results with adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX after curative resection. We aim to develop an imaging-derived biomarker to depict MVI-positive HCC patients more precisely and promote individualized treatment strategies of adjuvant HAIC. Patients with MVI-positive HCC were identified from five academic centers and utilized for model development (n=470). Validation cohorts were pooled from a previously reported prospective clinical study conducted (control cohort (n=145), adjuvant HAIC cohort (n=143)) (NCT03192618). The primary endpoint was recurrence-free survival (RFS). Imaging features were thoroughly reviewed, and multivariable logistic regression analysis was employed for model development. Transcriptomic sequencing was conducted to identify the associated biological processes. Arterial phase peritumoral enhancement, boundary of the tumor enhancement, tumor necrosis stratification, and boundary of the necrotic area were selected and incorporated into the nomogram for RFS. The imaging-based model successfully stratified patients into two distinct prognostic subgroups in both the training, control, and adjuvant HAIC cohorts (median RFS, 6.00 vs. 66.00mo, 4.86 vs. 24.30mo, 11.46 vs. 39.40mo, all P<0.01). Furthermore, no significant statistical difference was observed between patients at high-risk of adjuvant HAIC and those in the control group (P=0.61). The area under the receiver operating characteristic curve at two years was found to be 0.83, 0.84, and 0.73 for the training, control, and adjuvant HAIC cohorts respectively. Transcriptomic sequencing analyses revealed associations between the radiological features and immune-regulating signal transduction pathways. The utilization of this imaging-based model could help to better characterize MVI-positive HCC patients and facilitate the precise subtyping of patients who genuinely benefit from adjuvant HAIC treatment.

Postoperative adjuvant hepatic arterial infusion chemotherapy combined with donafenib in hepatocellular carcinoma with solitary large tumor and microvascular invasion: A multicenter, prospective, single-arm, phase II trial.

e16227 Background: Hepatocellular carcinoma (HCC) with solitary large tumor (≥ 5 cm) and microvascular invasion (MVI) was associated with high 5-year recurrence rate and poor survival prognosis. Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) was found to improve the recurrence-free survival (RFS) with acceptable safety profiles in HCC patients with MVI. However, the prognosis of HCC who received adjuvant HAIC after hepatectomy still remain far from satisfactory. Several studies have shown that the combination of HAIC and tyrosine kinase inhibitors (TKIs) could exhibit a synergistic anticancer effect and improve the survival outcomes of advanced HCC. Thus, the present study was conducted to explore the efficacy and safety of adjuvant HAIC plus the novel multikinase inhibitor donafenib in HCC with solitary tumor ≥ 5 cm and MVI. Methods: This prospective, single-arm phase II study was conducted in three medical centers in China. HCC patients with both solitary tumor ≥ 5 cm and MVI, no evidence of recurrence at radiological follow-up at 4-8 weeks after hepatectomy, no previous treatment for HCC other than hepatectomy, Child-Pugh score A or B7 were enrolled. Eligible patients received one cycle of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX4), and followed by donafenib (200 mg orally twice daily) for up to 1 year until disease recurrence or unacceptable toxicity. The primary endpoint was 1-year recurrence-free survival rate (1-year RFS rate). Secondary endpoints included RFS, overall survival (OS) and safety. Results: A total of 18 patients were included for analysis. The median age was 59 years (range, 28–75), the median maximum tumor size was 7.0 cm (interquartile range [IQR], 6.2–7.8), 88.9% had low-risk MVI, 61.1% had Edmondson-Steiner grade III-IV and 44.4% had incomplete tumour capsule. As of November 27, 2023, 4 of 18 patients (22.2%) recurrenced and no deaths occurred with a median follow-up of 15.0 months (95% confidence interval [CI], 5.1–19.1). The 1-year RFS rate was 64.9% (95%CI, 39.2%–100%), and current immature median RFS was 14.3 months (95%CI, not available [NA], 11.2–NA). The most common treatment-related adverse events (TRAEs) were hand-foot skin reaction (72.2%), diarrhea (38.9%), decreased platelet count (22.2%), hypoalbuminemia (22.2%), and alopecia (22.2%). Grade 3 TRAEs occurred in 6 patients (33.3%), and no grade 4 or 5 TRAEs occurred. Conclusions: In this prospective study, the preliminary data indicated that HAIC combined with donafenib is an encouraging adjuvant therapy with well-tolerated safety profiles for HCC patients with solitary tumor ≥ 5 cm and MVI. Clinical trial information: NCT04962958 .

Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis.

Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors. Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared. In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (P<0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P<0.05). But the OS rates of a-TACE and control groups showed no significant difference (P=0.279). Multivariate analysis identified a-HAIC (HR=0.449, P=0.000) and a-TACE (HR=0.633, P=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, P=0.003) was identified as an independent protective factor, too. Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.

Adjuvant hepatic arterial infusion chemotherapy in patients with resected hepatocellular carcinoma with microvascular invasion.

Adjuvant hepatic arterial infusion chemotherapy in patients with resected hepatocellular carcinoma with microvascular invasion.

Adjuvant hepatic arterial infusion pump chemotherapy after repeat hepatectomy for patients with liver confined recurrence of colorectal cancer – a phase ii study

Adjuvant hepatic arterial infusion pump chemotherapy after repeat hepatectomy for patients with liver confined recurrence of colorectal cancer – a phase ii study

The Effect of Histopathological Growth Patterns of Colorectal Liver Metastases on the Survival Benefit of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy

BackgroundHistopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM.MethodsPatients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan–Meier and Cox regression methods, respectively.ResultsWe included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32–0.73, p < 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45–0.82, p < 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72–2.32, p = 0.40).ConclusionsThere is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.

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

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

Postoperative hepatic arterial chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence: A multicenter randomized phase II trial (PRODIGE 43 - PACHA-01).

3515 Background: Hepatic arterial infusion (HAI) of chemotherapy (CTx) has been proposed as a potential treatment to decrease the risk of hepatic recurrence after resection of colorectal liver metastases (CRLM). Randomized controlled trials (RCTs) led to controversial results and meta-analyses are inconclusive. We conducted a comparative phase II RCT to assess the efficacy of adjuvant HAI oxaliplatin with concomitant intravenous (IV) CTx in pts at high risk of hepatic recurrence (≥4 resected CRLM). Methods: Pts who underwent curative-intent surgery of at least 4 CRLM after preoperative IV CTx were randomly assigned (1:1) to receive adjuvant IV fluorouracil/leucovorin (LV5FU2) combined with oxaliplatin (85mg/m2) by HAI (HAI-IV arm) or IV route (IV arm) every 2 weeks, for at least 3 months to achieve a minimal duration of perioperative CTx of 6 months. The primary endpoint was the hepatic recurrence free survival (h-RFS). Secondary endpoints included the feasibility of delivering at least 4 CTx cycles, toxicity (NCI-CTCAE 4.0) including HAI catheter-related complications, RFS, overall survival (OS) and recurrence pattern. 108 randomized pts were required to detect a gain in 18-month h-RFS from 30% to 50% with a one-sided α risk of 10% and 95% power. The primary endpoint was analyzed with a Cox regression model, with adjustment for stratification factors (tumor response to preoperative CTx and number of resected CRLM). The study was prematurely stopped after randomization of 99 pts due to recruitment issues and HAI catheters market withdrawal. Results: Between Jun 2015 and Dec 2020, 99 pts (median age, 62; median number of CRLM, 5) were randomly assigned in HAI-IV arm (50 pts) or IV arm (49 pts). After a median follow-up of 56 months, the intent-to-treat analysis showed a significantly longer h-RFS in the HAI-IV arm compared to the IV arm (median 25 [16-37] vs 12 months [8-21]; HR 0.598 [95%CI 0.379-0.944], p = 0.027). 5-year h-RFS was 32% [19-45] in the HAI-IV arm vs 13% [4-27] in the IV arm, respectively. Median and 5-year OS were 74 months [51-74] and 60% [43-74] in the HAI-IV arm vs 54 months [37-69] and 46% [29-61] in the IV arm (HR 0.551 [0.299-1.015], p = 0.056). The median number of postoperative CTx cycles was 6 in both groups with 86% and 78% of patients having received at least 4 cycles in HAI-IV and IV arms (p = 0.7), respectively. Grade 3-4 toxicity rate was 58% in the HAI-IV arm vs 31% in the IV arm (p = 0.01). Overall, nine pts (18%) experienced HAI-related complications. No toxic death occurred in both arms. Conclusions: Despite a higher but acceptable toxicity, combination of HAI oxaliplatin with IV LV5FU2 significantly improved h-RFS after curative resection of CRLM in high-risk patients. This combined treatment should be considered as a valid option for these patients. Clinical trial information: NCT02494973 .

Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX to improve outcomes of patients with hepatocellular carcinoma with microvascular invasion: A prospective multicenter, phase 3, randomized, controlled clinical trial.

4013 Background: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX (5- fluorouracil, leucovorin, and oxaliplatin) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). Methods: In this randomized, open label, multicenter, phase 3 trial, histologically confirmed HCC patients with MVI were randomized (1:1) to receive either 1 to 2 cycles of adjuvant HAIC-FOLFOX (treatment group) or routine follow-up without any adjuvant treatment (control group). The primary endpoint was disease free survival (DFS), Secondary endpoints included overall survival (OS), recurrence rate and safety. Survival rates were calculated by the Kaplan-Meier plots. Adverse events (AE) were graded according to NCI-CTCAE version 5.0. Results: Between June, 2016 and August, 2021, a total of 315 patients in 5 centers were enrolled in to the study and eligible patients were randomly assigned to the treatment group (n = 157) or control group (n = 158) and were included in the intention-to-treat (ITT) population. Among these 14 patients from treatment group and 15 patients from control group were excluded from the per-protocol (PP) population. 148 patients in treatment group underwent at least 1 cycle of HAIC were included in safety analyses. The median DFS of treatment group and control group were 27.0 months (95% CI, 17.0-37.0) and 11.3 months (95% CI, 7.9-14.7), respectively in ITT population, while which was 20.4 months (95% CI, 9.5-31.3) and 9.7 months (95% CI, 6.9-12.4), respectively in PP population. The DFS were significantly better in the treatment group than in the control group in both ITT population and PP population (p = 0.001 and &lt; 0.001, respectively). The DFS rates at 1, 2, and 3-years were 64.3%, 50.4%, and 44.3% in treatment group and 47.3%, 33.3%, and 24.2% in control group, respectively in ITT population, while which were 64.0%, 48.2%, and 42.2% in treatment group and 43.3%, 27.1%, and 18.4% in control group, respectively in PP population. The OS rates at 1, 2, and 3-year for the treatment group were 94.7%, 87.6%, and 80.5%, and were 91.9%, 85.9%, and 77.0% for the control group, respectively in ITT population, while which were 94.9%, 86.7%, and 80.9% in treatment group and 91.8%, 84.9%, and 75.3% in control group, respectively in PP population. Furthermore, in ITT population, there were 63 (40.1%) patients in the treatment group and 88 (55.7%) patients in the control group had recurrence. Majority of the AEs observed were grade 0-1 (n = 124 (83.8%)) and no treatment related death was observed during the study period. Conclusions: Postoperative adjuvant HAIC with FOLFOX significantly improved the survival benefits with acceptable toxicities in HCC patients with MVI. Clinical trial information: NCT03192618.

Adjuvant intra-arterial chemotherapy for patients with resected colorectal liver metastases: a systematic review and meta-analysis.

The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM. PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design. Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine. Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy.

Kirsten rat sarcoma (KRAS) oncogene mutation predicts magnitude of response and outcomes in hepatic arterial infusion pump therapy of unresectable colorectal liver metastases.

The Kirsten rat sarcoma (KRAS) mutation predicts negative outcomes following resection of colorectal liver metastases (CRLM) and adjuvant hepatic arterial infusion (HAI) pump chemotherapy. Less is known on the effects of KRAS mutation on tumor response in patients with unresectable CRLM undergoing HAI chemotherapy with floxuridine. This is a retrospective cohort study investigating the effects of KRAS mutation on tumor response in patients with unresectable CRLM treated with HAI chemotherapy. Primary endpoint was objective response rate (ORR), secondary endpoints included overall tumor response and conversion to resectability. Twenty-five patients with unresectable liver metastases from colorectal cancer were treated with HAI chemotherapy between 2017-2019. Median number of liver lesions was 12 (range, 1-59) and almost all (n=24) had prior chemotherapy before starting HAI therapy. Median number of cycles administered via HAI pump was 6 (range, 3-12). Overall decrease in liver tumor burden was 63.5% (median; range, -257-100%) with an ORR of 20/25 (80%) and 10 (40%) patients converting to resectable status. Eleven (44%) patients had KRAS positive tumors. When compared to wild-type, KRAS positive tumors had less overall percent decrease (58% vs. 70%; P=0.04) and ORR (7/11 vs. 13/13; P=0.03). Fewer patients with KRAS positive tumors converted to resectable status during HAI therapy (2/11 vs. 8/13; P=0.05). At a median follow-up of 14.6 months (range, 4.0-36.6 months), overall survival is 45% among KRAS-positive and 77% for wild type patients. KRAS mutational status in patients with unresectable liver metastases from colorectal cancer predicts worse response to HAI chemotherapy compared to wild type.

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy after Resection of Colorectal Liver Metastases; Surgical Complications, Toxicity, and Survival in a Prospective Study in the Netherlands

Background: Hepatic arterial infusion pump (HAIP) chemotherapy remains a promising treatment for patients with colorectal liver metastases (CRLM). The aim of this study was to investigate surgical complications, toxicity, and survival outcomes of patients who received adjuvant HAIP chemotherapy for CRLM. Methods: A single arm phase II study was performed in four centers. Patients with resectable CRLM without extrahepatic disease were eligible. An infusion pump was implanted after complete local treatment of CRLM followed by a maximum of 6 cycles of HAIP chemotherapy with floxuridine. Outcomes were 90 days pump-related major complications (Clavien Dindo grade ≥III), intra-arterial chemotherapy-related severe toxicity (CTCAE grade ≥III), and overall survival (OS). Results: Twenty-nine patients were included. Four patients (11.8%) had pump-related major complications, all requiring pump replacement; one for pump dysfunction, two for pump dislocation, and one for pump pocket infection. All patients started with HAIP chemotherapy. The median number of cycles was 5 (IQR 4-6), and the median cumulative dosage was 72% (IQR 55-85%). Ten patients (34%) required intra-arterial steroid treatment for biliary toxicity. Seven patients (24%) developed severe toxicity; five patients required stent-placement (three for biliary sclerosis/hyperbilirubinemia, two for persistent increase in liver enzymes without hyperbilirubinemia), one patient developed hepatic artery thrombosis, one patient required endoscopic extraction of an intrahepatic gallstone. Two-year OS was 93% (95%CI: 85-100%). Conclusion: Adjuvant HAIP chemotherapy for CRLM may result in major complications and severe toxicity; 1 in 7 patients required pump replacement and 1 in 6 patients required stent-placement for biliary sclerosis. Two-year OS was 93%.Tabled 1Patient and surgical characteristicsMedian [IQR] / n (%)Age at resection (years)57 [50-64]Clinical Risk Score (Fong score)2 [1-3]Preoperative systemic CTx9 (30)Major hepatectomy6 (21)Synchronous resection with primary CRC3 (10)Open ablation (with or without resection)11 (45)Surgery time (min)247 [204-300]Blood loss (mL)455 [187-762]Postoperative hospital stay (days)8 (6-9) Open table in a new tab

Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma.

Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively. This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC. A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes. Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p=0.364), sex (male: 25/28 vs. 35/36; p=0.435), and tumor size (median 9.55 vs. 8.10 cm; p=0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p=0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p=0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p=0.007) and OS (HR 0.095; p=0.007) for BCLC stage B/C HCC patients who received hepatectomy. Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.

Upfront liver resection in patients with resectable hepatocellular carcinoma with portal vein tumor thrombus

Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and inferior vena cava to right atrium tumor thrombus (IVCRATT) are worst condition of HCC. Median survival times (MST) of PVTT or RATT have been reported as 6 months and 4 months, respectively. According to the Japanese clinical guidelines, liver resection, TACE, arterial infusion chemotherapy, and molecular targeting therapy are recommended. Recently, liver resection showed better survival rate compared to non-liver resection according to the Japanese national database. Of course, mortality after liver resection is low. Furthermore, curative liver resection with adjuvant hepatic arterial infusion chemotherapy improved survival based on the Japanese HBP surgery group. According to those reports, HCC might cure by upfront liver resection although HCC showed PVTT. Furthermore, latest molecular targeting therapy (Lemvatinib) showed better response in patients with recurrent HCC after tumor thrombectomy when the HCC cells showed positive for EGFR. We therefore recommend upfront liver resection in patients with HCC with resectable PVTT and/or IVCRATT.

Safety and Feasibility of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy in Patients with Resectable Colorectal Liver Metastasis; A Phase II Trial in the Netherlands

Safety and Feasibility of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy in Patients with Resectable Colorectal Liver Metastasis; A Phase II Trial in the Netherlands

Recurrence After Liver Resection of Colorectal Liver Metastases: Repeat Resection or Ablation Followed by Hepatic Arterial Infusion Pump Chemotherapy

BackgroundThe aim of this study was to investigate the effectiveness of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after complete resection or ablation of recurrent colorectal liver metastases (CRLM).MethodsA retrospective cohort study was conducted of patients from two centers who were treated with resection and/or ablation of recurrent CRLM only between 1992 and 2018. Overall survival (OS) and hepatic disease-free survival (hDFS) were estimated using the Kaplan–Meier method. The Cox regression method was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CI).ResultsOf 374 eligible patients, 81 (22%) were treated with adjuvant HAIP chemotherapy. The median follow-up for survivors was 65 months (IQR 32–118 months). Patients receiving adjuvant HAIP were more likely to have multifocal disease and receive perioperative systemic chemotherapy at time of resection for recurrence. A median hDFS of 46 months (95% CI 29–81 months) was found in patients treated with adjuvant HAIP compared with 18 months (95% CI 15–26 months) in patients treated with resection and/or ablation alone (p = 0.001). The median OS and 5-year OS were 89 months (95% CI 52–126 months) and 66%, respectively, in patients treated with adjuvant HAIP compared with 57 months (95% CI 47–67 months) and 47%, respectively, in patients treated with resection and/or ablation only (p = 0.002). Adjuvant HAIP was associated with superior hDFS (adjusted HR 0.599, 95% CI 0.38–0.93, p = 0.02) and OS (adjusted HR 0.59, 95% CI 0.38–0.92, p = 0.02) in multivariable analysis.ConclusionAdjuvant HAIP chemotherapy after resection and/or ablation of recurrent CRLM is associated with superior hDFS and OS.

Addition of adjuvant hepatic artery infusion to systemic chemotherapy following resection of colorectal liver metastases is associated with reduced liver-related mortality.

After resection of colorectal liver metastases (CRLM), recurrent disease in the liver is a major cause of death but may be reduced with the addition of adjuvant hepatic arterial infusion (HAI) chemotherapy to systemic chemotherapy (SYS). This study investigates organ-specific causes of death in patients receiving adjuvant HAI and SYS compared to adjuvant SYS alone. Between 2000 and 2007, patients undergoing complete CRLM resection were identified from a prospectively maintained liver resection database and categorized as receiving HAI + SYS or SYS only. Using newly constructed definitions, mortality was attributed to specific organs (liver, lung, peritoneum, and brain) or infection. Univariate models and cumulative incidence functions were generated using competing risk methods. Of 361 eligible patients, 208 (57.6%) received HAI + SYS and 153 (42.4%) received SYS. The median follow up among survivors was 142 months (range = 12-217 months). Ten-year overall survival was 50.6% in the HAI + SYS group compared to 30.9% in those receiving SYS (P = .004). The 5-year cumulative incidence of liver-related mortality was 6.8% in the HAI + SYS group compared to 14.3% in the SYS group (P = .007). The addition of HAI to SYS after CRLM resection is associated with a 50% reduction in liver-related mortality at 5 years.

Adjuvant hepatic arterial infusion pump chemotherapy after resection of colorectal liver metastases; results of a safety and feasibility study in the Netherlands

Adjuvant hepatic arterial infusion pump chemotherapy after resection of colorectal liver metastases; results of a safety and feasibility study in the Netherlands

Adjuvant hepatic arterial infusion pump chemotherapy after resection of colorectal liver metastases; a phase II trial

Introduction: Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy demonstrated promising results with a median overall survival of 67 months (n=785) versus 44 months without HAIP (n=1.583, p<0.001) in a propensity scored analysis in patients with resectable colorectal liver metastases (CRLM).[J Clin Onc;35(17):1938] However, its general application is limited. Previous results from Memorial Sloan Kettering Cancer Center (MSKCC) should be confirmed in a randomized controlled trial (RCT) outside MSKCC. The aim of this study was to investigate the feasibility and safety of HAIP chemotherapy in a multicenter setting in the Netherlands. Materials & Methods: A phase II study was performed in two high-volume centers in the Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients were scheduled for 6 cycles of adjuvant HAIP chemotherapy with floxuridine, after complete resection of CRLM with pump placement. The main endpoints were feasibility (defined as successful administration of at least one cycle of HAIP chemotherapy) and safety (defined as 90-day postoperative complications). Result(s): Twenty patients with resectable CRLM were included. The median age of patients was 57 years (range 42-75). The median clinical risk score was 2 (range 1-5). All 20 patients (100%) received at least one dose of HAIP chemotherapy at a median of 42.5 days (range 26-57) after surgery. Pump related postoperative complications occurred in 2 patients (10%); replacement of a malfunctioning pump and repositioning of a flipped (upside down) pump. No arterial hemorrhage or dissection, extrahepatic perfusion, catheter related problems, pump pocket hematoma or pump pocket infections were found within 90-days after resection and implantation. Conclusion(s): Adjuvant HAIP chemotherapy in patients with resectable CRLM is safe and feasible as demonstrated in a phase II study of 20 patients. The PUMP trial (NTR 7493) has started to investigate the effectiveness of adjuvant HAIP chemotherapy in a randomized controlled trial.