Hepatic Arterial Infusion Pump Chemotherapy Research Articles

ASO Author Reflections: Application of Robotic Technique for Treatment of Biliary Sclerosis from Hepatic Artery Infusion Pump Chemotherapy.

ASO Author Reflections: Application of Robotic Technique for Treatment of Biliary Sclerosis from Hepatic Artery Infusion Pump Chemotherapy.

Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.

Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma.

Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2days after robotic placement versus 5 days after open HAIP placement (p<0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar-36% (8/22) after robotic placement versus 39% (11/28) after open placement (p=1.000). The median length of hospital stay was shorter in the robotic group-3 versus 5 days (p<0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p=0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p=0.153). Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications

IntroductionThis study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. MethodsThe first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. ResultsPatients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0–2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. ConclusionMethylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.

433 Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Results: From January 2020 until September 2022, 50 patients with advanced iCCA were included. Combined HAIP and systemic chemotherapy was administered to 38 patients (76.0%). Eleven patients (22.0%) received HAIP chemotherapy alone, because they had received systemic treatment before enrollment. One patient (2.0%) didn’t start treatment, because he died 19 days after pump implantation due to COVID-19. The median follow-up was 26.4 months (95% CI: 21.7 – 39.0). The median OS was 22.1 months (95% CI: 19.7 – not reached). The 1-year OS rate was 80.0% (95% CI: 69.6% – 91.9%); the 3-year OS rate was 28.6% (95% CI: 16.0% – 51.2%). The median PFS was 10.0 months (95% CI: 8.7 – 12.2). An objective response on imaging (RECIST) was achieved in 27 patients (54.0%) and disease control at 6 months in 43 patients (86.0%). Four patients (8.0%) underwent a resection after HAIP chemotherapy of whom 2 patients had a complete pathologic response. Conclusions: Combined HAIP with systemic chemotherapy for patients with advanced iCCA was associated with a favorable 3-year OS of 28.6% compared with 2.8% after systemic chemotherapy alone in the ABC trials. Clinical trial information: NL8234 .

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

Postoperative hepatic arterial infusion pump chemotherapy after resection of multinodular colorectal liver metastases

Postoperative hepatic arterial infusion pump chemotherapy after resection of multinodular colorectal liver metastases

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: a multicenter phase II trial

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: a multicenter phase II trial

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma

BackgroundA post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA.MethodsWe retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center.ResultsIn total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p < 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39).ConclusionsThis study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.

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.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day.With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival.

The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001). In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases

BackgroundFloxuridine’s high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine. MethodsPatients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed. Results265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472–0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470–0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463–0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257–0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation.The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %−37.8 %) over a period of 15 days (n = 18). ConclusionOverall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time.

Regional Therapy for Colorectal Cancer Liver Metastases: Which Modality and When?

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control.

Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07). This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overallsurvival(OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment

BackgroundThe aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics. MethodsConsecutive patients after complete resection of CRLM were included from two centres (1992–2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities. ResultsA total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29–32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%. ConclusionsTen-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers.