Adjuvant Hepatic Arterial Infusion Chemotherapy Research Articles

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.

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.

Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis

BackgroundAdjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC).MethodsRandomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs).ResultsThe present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56–0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49–0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19–0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19–0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21–0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60–0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36–0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43–0.75; p < 0.01), respectively).ConclusionThis meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.

Short-term outcomes of hepatic artery infusion chemotherapy for resected colorectal liver metastases

Background: Adjuvant hepatic artery infusion (HAI) chemotherapy in patients with colorectal liver metastasis (CRLM) has demonstrated survival benefit over systemic chemotherapy alone. However, this surgical approach has been offered only at a few centers as of recently. As new HAI centers emerge, it is important to better understand patient outcomes and survival associated with this surgical approach.

ASO Visual Abstract: Genomic Predictors of Recurrence Patterns After Complete Resection of Colorectal Liver Metastases and Adjuvant Hepatic Artery Infusion Chemotherapy.

ASO Visual Abstract: Genomic Predictors of Recurrence Patterns After Complete Resection of Colorectal Liver Metastases and Adjuvant Hepatic Artery Infusion Chemotherapy.

Genomic Predictors of Recurrence Patterns After Complete Resection of Colorectal Liver Metastases and Adjuvant Hepatic Artery Infusion Chemotherapy.

Despite curative hepatectomy, most colorectal liver metastasis (CRLM) patients relapse locally within 2 years. Genomic predictors for hepatic recurrence are poorly understood. This study was designed to identify genomic signatures for recurrence in resected CRLM patients treated with adjuvant hepatic artery infusion (HAI) and/or systemic (SYS) chemotherapy. Patients undergoing curative hepatectomy and adjuvant HAI+SYS or SYS between January 2000 and October 2017 with next-generation sequencing data were catalogued. Gene and signaling-level alterations were checked for association with time to any (AR), liver (LR), and extrahepatic recurrence (ER) by using Kaplan-Meier analysis. Of 172 receiving HAI+SYS, 100 patients recurred, with 69 LR and 83 ER. Five- and ten-year LR-free rates were 57% (95% confidence interval [CI] 48-65%) and 51% (95% CI 41-60%), respectively. Five- and 10-year ER-free, rates were 51% (95% CI 43-58%) and 45% (95% CI 36-54%), respectively. More ER was observed with tumors harboring altered KRAS (38% [95% CI 25-50%] vs. 63% [95% CI 53-71%], p-adj=0.003) and RAS/RAF (36% [95% CI 25-48%] vs. 66% [95% CI 56-74%], p-adj<0.001) than wild-type. Co-altered RAS/RAF-TP53 was associated with worse AR (26% [95% CI 14-40%] vs. 48% [95% CI 39-57%], p-unadj<0.001), ER (30% [95% CI 17-45%] vs. 62% [95% CI 53-70%], p-unadj<0.001), and LR rate (40% [95% CI 24-57%] vs. 70% [95% CI 60-77%], p-unadj=0.002). On multivariable analysis, controlling for clinical risk score, ablation, margin status, and primary T-stage, co-altered RAS/RAF-TP53 was associated with increased risk for AR (HR=2.14, 95% CI 1.38-3.31, p-unadj<0.001), LR (HR=1.79, 95% CI 1.06-3.02, p-unadj=0.029), and ER (HR=2.81, 95% CI 1.78-4.44, p-unadj<0.001). Altered KRAS, RAS/RAF, and RAS/RAF-TP53 associated with earlier local and distant recurrence in resected CRLM patients receiving adjuvant HAI+SYS. Co-altered RAS/RAF-TP53 was a novel predictor of LR warranting investigation of whether genomic cooperativity is associated with this relapsing phenotype. Systemic therapies tailored to high-risk tumor biology are needed to reduce distant relapse after hepatectomy.

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.

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.

Adjuvant treatment strategy after curative resection for hepatocellular carcinoma.

Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.

Extrahepatic recurrence rates in patients receiving adjuvant hepatic artery infusion and systemic chemotherapy after complete resection of colorectal liver metastases.

This study investigated the effect of the reduced dose of systemic chemotherapy (SYS) on recurrence patterns in patients receiving adjuvant hepatic artery infusion (HAI) chemotherapy after complete colorectal liver metastases (CRLM) resection. Patients undergoing complete CRLM resection between 2000 and 2007 were selected from a prospectively maintained database and categorized as receiving SYS or HAI + SYS. Those with pre and/or intraoperative extrahepatic disease, documented death, or recurrence within 30 days of CRLM resection were excluded. Competing risk, Fine and Gray's tests were used to compare SYS versus HAI + SYS for time-to-organ recurrence. Of 361 study patients, 153 (42.4%) received SYS and 208 (57.6%) received HAI + SYS. The median follow-up for survivors was 100 (range = 12-185) and 156 months (range = 18-217) for SYS and HAI + SYS, respectively. The 5-year cumulative incidence (CI) of any liver recurrence was greater for those receiving SYS (SYS = 41.9% vs. HAI + SYS = 28.6%, p = .005). The 5-year CI of developing any lung or extrahepatic recurrence for SYS patients was 36.2% and 47.9% compared with 44.5% (p = .242) and 51.7% (p = .551), respectively, in patients receiving HAI + SYS. Despite the reduced dose of SYS, adjuvant HAI + SYS after CRLM resection is not associated with a significantly increased risk of extrahepatic recurrence.

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 Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases: A Retrospective Analysis of 674 Patients.

To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

Impact of adjuvant hepatic arterial chemoinfusion using high-dose 5-fluorouracil with systemic gemcitabine for pancreatic cancer: A propensity score–matched analysis.

402 Background: The aim of this retrospective study was to evaluate the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) using high-dose 5-fluorouracil with systemic gemcitabine on prognosis of resected pancreatic cancer. Methods: Between January 2006 and April 2016, 298 patients underwent elective pancreatic resection for resectable or borderline resectable pancreatic cancer at Nara Medical University Hospital. Patients who received adjuvant HAI plus systemic gemcitabine after surgery (HAI group) were compared with those who received systemic chemotherapy alone (control group). Patients were propensity score matched for age, sex, ASA score, CA19-9, NCCN resectability status, neoadjuvant treatment, surgical procedure, portal vein invasion, T stage, N stage, and margin status. Results: 224 patients with resectable or borderline resectable pancreatic cancer were enrolled in this study. 151 patients in the HAI group and 73 patients in the control group were included. Propensity score matching analysis was used to identify 63 well-balanced patients in each group for overall survival comparison. The estimate overall survival (OS) for patients treated with HAI was longer than patients without HAI in both the whole cohort (median OS, 54 vs. 24 months, respectively; P &lt; 0.001) or matched cohort (median OS, 58 vs. 26 months, respectively; P = 0.003). The liver was only recurrence site in which significant decrease was observed in the HAI group compared to the control group ( P = 0.031). In the multivariate analysis, adjuvant chemotherapy without HAI were independently associated with worse outcome in the whole cohort. A total of 127 patients in the HAI group (84%) had completed the planned dose of HAI. The remaining 24 patients stopped treatment before the end of the planned cycle due to catheter-associated complications in 9 (6.0%) and development of liver abscess in 2 (1.3%). No treatment-related deaths occurred. Conclusions: The efficacy of hepatic arterial chemoinfusion as adjuvant treatment for resectable pancreatic cancer should be revisited.

Significance of hepatic resection and adjuvant hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombus in the first branch of portal vein and the main portal trunk: a project study for hepatic surgery of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the major portal vein (PV) is extremely poor. The purpose of this study was to clarify the impact of hepatic resection for HCC with tumor thrombus in the major PV. Four hundred patients undergoing macroscopic curative resection for HCC involving the first branch or trunk of the PV between 2001 and 2010 at the 22 institutions were enrolled. We examined the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) on prognosis and validated the prognostic index consisting of ascites, prothrombin activity, and maximal tumor diameter. Median survival time (MST) and 5-year overall survival rate were 21.5months and 25.7%. MST of HAIC group was longer than that of non-HAIC group (28.1months vs. 18.7months, P = 0.0024). Significant prognostic factors for overall survival were PIVKA-II, tumor diameter, and adjuvant HAIC. MST for patients with prognostic index 0, 1, 2, and 3 was 39.0, 21.1, 18.9, and 5.7months, respectively (P = 0.005). Macroscopic curative resection with adjuvant HAIC might provide better survival outcome. Furthermore, the prognostic index was useful to select adequate treatment modalities for patients with HCC with tumor thrombosis in the major PV.

Long term follow-up for hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin after curative resection of hepatocellular carcinoma

Background and aims: Many recent studies suggest that postoperative hepatic artery-infusion chemotherapy (HAIC) in hepatocellular carcinoma(HCC) can effectively and safely reduce intrahepatic recurrence and improve the overall survival. In this study, we investigated 10 years follow-up of patients who underwent HAIC after curative resection of HCC. Materials and methods: We retrospectively reviewed medical records in last 10 years follow-up period of prospectively recruited HCC patients who underwent the adjuvant HAIC with 5-FU and cisplatin after curative resection of HCC. Total 128 patients were included and 31 patients underwent HAIC who were highly suspected recurrence in final pathologic report. Every 4 weeks, four cyscles of HAIC were given to patients in HAIC group. Results: . Platelet count and alpha-fetoprotein (AFP) levels HAIC group were higher than non-HAIC group in statistically. However MELD score was higher in non-HAIC group. Proportion of above T2 and portal vein, microvascular invasion in HAIC group were statistically different from non-HAIC group. There were no statistically differences between two groups regarding to not only overall survival (p value=0.568) but also disease-free survival (p value=0.975). Even after propensity score matching, there were no statistically significant differences in analysis of overall survival (p value=0.740) and disease-free survival (p- value=0.769). In subgroup analysis, especially above T2, HAIC group seems to be more favorable in overall survival, however there was no statistically significance between two groups (p value=0.512). Conclusion: In this study, we could not find any statistical oncologic benefit in long-term overall survival and disease-free survival in statistically.

Impact of adjuvant hepatic arterial infusion chemotherapy using high-dose 5-fluorouracil with systemic gemcitabine for resectable pancreatic cancer.

360 Background: Despite recent advances in cancer treatment, postoperative recurrence remains an unsolved issue for resectable pancreatic cancer. To prevent hepatic recurrence and prolong postoperative survival, we introduced postoperative adjuvant chemotherapy of high-dose 5-fluorouracil (5-FU) hepatic arterial infusion (HAI) with systemic chemotherapy using gemcitabine in 2006. We retrospectively evaluated the clinical impact of HAI. Methods: A total of 251 patients who underwent pancreatic resection for PC were analyzed. Patients received weekly high-dose 5-FU through the hepatic artery using a port-catheter system (1000 mg/m2 for 5 h) plus concurrent systemic gemcitabine (1000 mg/m2) followed by systemic 3 cycles of gemcitabine or 4 cycles of S-1. Patients were divided into two groups. The patients who completed planned adjuvant chemotherapy of HAI were classified as the completion group (HAI), and the patients who failed to complete HAI or received systemic adjuvant chemotherapy other than HAI were classified as the control group. Results: One hundred thirty-eight patients (55%) completed planned adjuvant chemotherapy of HAI. On the other hand, 28 patients (11%) failed to complete HAI and 85 patients (34%) received systemic adjuvant chemotherapy alone. The reasons for incompletion of HAI were as follows: any recurrence during HAI treatment in 8, poor general condition of patients in 4, hepatic arterial stenosis in 4 and catheter trouble in 3. Initial hepatic metastasis rate was significantly lower in the HAI group than the control group (15.2 vs. 26.3%, p=0.029), and liver metastasis free survival was significantly better in the HAI group than the control group (p=0.001). The HAI group had a better prognosis than the control group (58.1 vs. 26.9M, p &lt; 0.001). Prognostic factor analysis indicated that failure to complete HAI (p &lt; 0.001, HR 1.95), borderline resectable tumor (p = 0.028, HR 1.63), and lymph node metastasis (p = 0.018, HR 1.59) were the independent adverse prognostic factors. Conclusions: Our data demonstrate that HAI can significantly prevent hepatic recurrence and also improve the postoperative prognosis in pancreatic cancer.

Association of adjuvant hepatic artery infusion chemotherapy after resection of colorectal liver metastases with improved survival in patients with both right- and left-sided primary tumors.

776 Background: Patients with a right-sided (R) and/or KRAS-mutated (KRAS-MUT) primary tumors have inferior outcomes compared to patients with left sided (L) and/or KRAS-wildtype (KRAS-WT) cancers. Adjuvant hepatic artery pump infusion (HAI) chemotherapy improves overall survival (OS) in patients with colorectal liver metastases (CRLM). We investigated the impact of HAI in relation to the laterality and KRAS status of the primary tumors. Methods: Patients with resected CRLM and available KRAS-status, treated with and without adjuvant HAI were reviewed from a prospective institutional database. Rectal tumors were excluded. Correlations between adjuvant HAI, clinicopathological factors including laterality, KRAS status and OS were analyzed. Cox proportional hazard regression was used to assess survival outcomes comparing R (cecum to transverse colon, excluding appendix) versus L (splenic flexure to sigmoid) colon cancers. Results: 490 patients (R, n = 183; L, n = 307) were evaluated between 1993-2012 (median follow up of 6.5 years). Fifty-six percent (n = 277) received adjuvant HAI. Adjuvant HAI was associated with improved median OS in both R (7.0 vs. 4.4 years, p = 0.006) and L tumors (10.5 vs. 5.4 years, p &lt; 0.01). On multivariate analysis, HAI remained associated with improved OS (HR 4.49, p = 0.001) independent of primary tumor site and other clinical predictors (Table). Conclusions: Adjuvant HAI after resection of CRLM is independently associated with improved OS regardless of laterality of primary tumor. Treatment with adjuvant HAI correlates with improved prognosis in patients with resectable L/KRAS-MUT and R/KRAS-WT tumors. The biological difference for these outcomes requires further investigation. [Table: see text]