Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center.

Methods

Patients who underwent HAIP placement (2021–2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska–Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan–Meier method and Cox proportional hazards model, respectively.

Results

Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months.

Conclusions

HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.

1 Introduction

Colorectal cancer is one of the most common noncutaneous cancers in the United States, with prognosis heavily dependent on stage. Patients with early-stage colon cancer have a 5-year survival rate of > 90%, whereas those with metastatic disease have a 5-year overall survival (OS) of only 13% [1]. The liver remains one of the most common sites of distant metastasis for colorectal cancer. When technically feasible, resection of isolated liver metastases can be performed with curative intent [2]. However, only 15%–20% of patients with colorectal liver metastasis (CRLM) present with resectable disease [3]. This may be due to patient status, inadequate future liver remnant or anatomical constraints with biliary drainage, venous outflow, or arterial/venous inflow [4].

Earlier studies demonstrated a preferential perfusion of CRLM through the hepatic arterial system. This is contrary to liver parenchyma derivation of oxygen and nutrients from the portal venous system [5]. Hepatic artery infusion pump (HAIP) therapy takes advantage of liver specific dual inflow vascular anatomy in addition to this anatomic relationship to directly deliver high doses of chemotherapy to target lesions [6]. Moreover, regional delivery of cytotoxic therapy minimizes the systemic side effects. Currently, Floxuridine (FUDR), a drug derivative of the ubiquitously used antimetabolite 5-fluorouracil (5-FU), is predominantly utilized as a standard agent for HAIP therapy. Specific pharmacokinetics of FUDR with a short half-life and high first-pass metabolism in the liver makes it an ideal therapeutic agent for HAIP treatment [6].

HAIP chemotherapy is increasingly being utilized for the treatment of CRLM [7, 8]. Currently, HAIP therapy is limited to select high-volume centers due to complexity of the operation and, importantly, due to intensive postoperative management. However, the adoption is increasing across the United States and worldwide due to its potential efficacy [9]. Limited level 1 data exist to support its efficacy in the era of modern chemotherapy, but in phase II trials it shows favorable results regarding OS and conversion to resection [10]. The most frequent indication is in the setting of unresectable and of high-risk yet resectable CRLM, but additional indications include intrahepatic cholangiocarcinoma [11, 12]. Moreover, the role of HAIP therapy in the treatment sequence for unresectable CRLM is currently under investigation [13, 14]. Current recommendations are to utilize HAIP in the second-line setting in combination with systemic chemotherapy, or as adjuvant therapy after resection or ablation for CRLM [3]. HAIP can also be considered as a first or second line therapy for unresectable ICC [15].

Herein we describe the HAIP program experience of implementing a HAIP program at initial 2 years at a free-standing cancer hospital embedded within a major university.

2 Materials and Methods

2.1 Data Collection

All patients who underwent HAIP placement at The James Cancer Hospital at The Ohio State University, Columbus, OH, USA between January 2021 and October 2023 were included (IRB #2023C0177). The database was created by retrospective chart review by two authors (Julia Monasterio, Taylor Neilson) and verified by two separate authors (RCC, SMR). Demographic, clinical, pathologic, and treatment variables were collected and maintained in a deidentified database. Response in the liver was determined using RECIST criteria based on the radiology report in the patient's medical record [16].

2.2 Description of Technique

HAIP placement was performed by expert surgeons who were previously trained in the technique at a high-volume center (AT, ACK). The first 26 procedures were performed open and two were performed robotically [17]. The technique is similar to that described elsewhere [11]. The procedure begins with mobilization of the liver, cholecystectomy, common hepatic artery lymphadenectomy and identification of the gastroduodenal artery (GDA). The GDA is dissected out for a length of approximately 1–2 cm. Next, the pump pocket is created and the catheter is passed through a tunnel from the pump to the right upper quadrant of the abdomen. The pump is secured to the fascia. The GDA is test clamped and Doppler is used to confirm flow in the proper hepatic artery. The distal GDA is suture ligated, flushed through a transverse arteriotomy, and the catheter is placed with the tip ending at the bifurcation of the GDA from the common hepatic artery. Fluorescein or indocyanine green is injected into the catheter to confirm perfusion. The port is injected with heparinized saline. The pump is typically placed before primary tumor resection (PTR), but following any planned liver resection or ablation.

2.3 Statistical Analysis

Categorical and continuous variables were compared using Chi-square and Kruskal–Wallis tests, respectively. Survival estimates were calculated using the Kaplan-Meier method and comparisons were made with the log-rank test at α = 0.05. OS was determined from both date of diagnosis and from HAIP placement. Progression-free survival (PFS) was defined as documentation of progressive disease or death from any cause and was calculated from date of HAIP placement. Hazard ratios for survival were calculated with univariate and multivariable Cox regression models. Variables with a statistically significant hazard ratio for survival (p < 0.10) were used to construct a multivariate Cox regression model. Statistical analyses were conducted in SPSS (IBM).

3 Results

3.1 Demographics—Entire Population

Thirty-two patients underwent attempted HAIP placement. Median age was 51.2 years, most had an ECOG score of 0 or 1 (96.9%), were male (71.9%), and had no major comorbidities (90.6%, Table 1). Synchronous CRLM was the most common indication for HAIP (78.1%), followed by metachronous CRLM (15.6%) and unresectable cholangiocarcinoma (6.3%). The median Clinical Risk Score was 4; 16 (61.5%) had node-positive primary tumors, 23 (88.5%) had less than 12 months disease-free interval, all had multifocal disease, nine (34.6%) had carcinoembryonic antigen (CEA) over 200, and 12 (46.2%) had at least one tumor over 5 cm in diameter (Table 2) [18].

Table 1. Demographics of patients who underwent operation for HAIP placement.

Demographic	Category	n (%)
Age (years)	Median ± SE	51.2 ± 1.94
ECOG	0	21 (65.6)
	1	10 (31.3)
	2	1 (3.1)
Race	Black	2 (6.2)
	Other	1 (3.1)
	White	29 (90.6)
Gender	Female	9 (28.1)
Gender	Male	23 (71.8)
BMI (kg/m²)	Median ± SE	28.8 ± 1.13
Charlson comorbidity index	0	29 (90.6)
	1	0 (0.0)
	2	2 (6.3)
	3	0 (0.0)
	4	1 (3.1)
Inherited syndrome	No	31 (96.9)
Inherited syndrome	Yes	1 (3.1)

Abbreviations: BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; SE, standard error.

Table 2. Clinicopathologic findings of patients who underwent operation for HAIP placement.

Variable	Category	n (%)
CEA	Median ± SE	202.6 ± 319.5
Primary tumor location	Biliary Tract	3 (9.4)
	Left Colon	18 (56.3)
	Right Colon	5 (15.6)
	Rectum	6 (15.6)
Somatic mutation status	APC	1 (3.1)
	BRAF	1 (3.1)
	KRAS	8 (25.0)
	Multiple	4 (12.5)
	None	14 (43.8)
	Unknown	3 (9.4)
Mismatch repair deficiency	Yes	3 (9.4)
Mismatch repair deficiency	No	27 (84.4)
Timing	Synchronous	25 (78.1)
	6–24 months	1 (3.1)
	> 24 months	4 (12.5)
	N/A	2 (6.3)
Multiagent chemo before HAIP	Yes	28 (87.5)
Multiagent chemo before HAIP	No	4 (12.5)

Abbreviations: APC, adenomatous polyposis coli; BRAF, v-Raf murine sarcoma viral oncogene homolog B; CEA, carcinoembryonic antigen; HAIP, hepatic artery infusion pump; KRAS, Kirsten rat sarcoma virus; SE, standard error.

Ultimately, HAIP was performed in 28 patients (87.5%). Four patients failed to successfully undergo HAIP placement. One was aborted because the patient had a diminutive GDA and thus no target for catheter insertion, two were aborted due to discovery of peritoneal metastases, and one was aborted due to evidence of portal hypertension in the operating room in a patient with long-standing unresectable intrahepatic cholangiocarcinoma.

3.2 Technical Success and Complications

All patients who underwent HAIP placement were able to receive FUDR. Most often, complete perfusion was achieved before leaving the operating room (n = 21, 75.0%). Of those who had incomplete perfusion, four required postoperative embolization of the nonperfused hepatic artery branch (right or left) and subsequently had complete perfusion of the diseased hemi-liver.

The overall complication rate was 37.5%. Complication rate at 30 days was 0% and at 90 days was 3.6%. In patients who had HAIP placed for CRLM, the most common complication was biliary stricture (23.1%), followed by extrahepatic perfusion (3.8%) and superficial surgical site infection (3.8%). None of the patients who experienced biliary complications had concomitant perfusion complications. Additionally, none were on systemic bevacizumab during HAIP therapy. All patients with biliary complications received more than 6 months of HAIP therapy. No clinicopathologic features demonstrated a statistically significant association with risk of biliary complications. One pump had to be removed due to dislodgement during a subsequent operation, although the patient was no longer receiving FUDR at the time due to disease progression (Table 2).

3.3 Survival

Survival analyses were performed only for those who had HAIP placed for CRLM. Median OS was 55.2 months (95% CI 20.3–90.0 months) from date of diagnosis (Figure 1). Median OS was 20.5 months (95% CI 12.2–28.8 months) from pump placement (Figure 2), and PFS from pump placement was 7.8 months (95% CI 3.8–11.9 months, Figure 3). Median duration of HAIP therapy was 9.2 months (SD + /− 8.1 months).

Details are in the caption following the image — **Figure 1**
Open in figure viewer PowerPoint

Kaplan–Meier curve demonstrating overall survival estimate when calculated from date of diagnosis.

Factors examined on univariate Cox regression and their associated hazard ratios are summarized in Table 3. Only age > 70 (HR 5.6, 95% CI 1.13–28.2) and liver-specific disease progression (HR 2.56, 95% CI 0.13–1.18) were associated with worse OS. On multivariable Cox regression, neither age nor progression in the liver were significantly associated with OS.

Table 3. Variables, number of patients per category, hazard ratios, and p-values calculated based on Cox proportional hazards model for overall survival from date of hepatic artery infusion pump (HAIP) placement.

Variable	Category	n (%)	HR	p-value
Age	< 70	24 (92.3)	ref	—
Age	> 70	2 (7.7)	5.650	0.035*
Gender	Male	18 (69.2)	ref	—
Gender	Female	8 (30.8)	1.300	0.649
BMI	< 30	16 (61.5)	ref	—
BMI	> 30	10 (38.5)	0.525	0.286
Side	Right	5 (19.2)	ref	—
	Left	16 (61.5)	1.450	0.642
	Rectum	5 (19.2)	1.200	0.857
Charlson comorbidity index	0	24 (92.3)	ref	—
	1	0 (0.0)	n/a	—
	2	2 (7.7)	2.230	0.453
CEA	< 200	9 (34.6)	ref	—
	> 200	9 (34.6)	1.765	0.406
	Unavailable	8 (30.8)	1.221	0.780
Duration HAIP therapy	> 6mo	22 84.6)	ref	—
Duration HAIP therapy	< 6mo	4 (15.4)	2.217	0.325
Timing	Synchronous	22 (84.6)	ref	—
Timing	Metachronous	4 (15.4)	1.324	0.675
Concurrent	Yes	18 (69.2)	ref	—
Concurrent	No	8 (30.8)	1.003	0.996
Adjuvant	Yes	4 (15.4)	ref	—
Adjuvant	No	22 (84.6)	3.217	0.267
PD on HAIP	Yes	21 (80.8)	ref	—
PD on HAIP	No	5 (19.2)	0.033	0.260
PD in liver	Yes	10 (38.5)	ref	—
PD in liver	No	16 (61.5)	0.391	0.095*

Abbreviations: BMI, body mass index; CEA, carcinoembryonic antigen; PD, progressive disease.
* denotes statistical significance at p < 0.10.

3.4 Liver-Specific Response

At 12 months after pump placement, there was one complete response, one without evidence of disease after concurrent ablation, and two partial responses. Of those who progressed, six patients had stable hepatic disease with extrahepatic progression, and 17 had progressive liver disease. Four patients were converted to resectable disease. Among those who progressed in the liver, median time to progression was 6.8 months.

Adjuvant HAIP was planned in four patients. All four of these patients underwent concurrent ablation with or without parenchyma-sparing hepatectomy. There were no significant complications within this cohort. At last contact, two of these patients remained without evidence of disease. Patients who had progression in the liver had clinically inferior, but no statistically significant difference in OS (14.7 months vs. 20.5 months, p = 0.085, Figure 4).

3.5 Systemic Chemotherapy

All patients received systemic chemotherapy before or concurrent with HAIP. Of those with CRLM who had HAIP, 23 (88.5%) had previously been treated with systemic chemotherapy. The most common regimens were 5-FU with oxaliplatin and/or irinotecan, in combination with bevacizumab (50%). Four patients (15.3%) were treated with an epidermal growth factor receptor (EGFR) inhibitor and 5-FU backbone. The majority of patients (57.7%) were treated with HAIP and concurrent systemic therapy; the most common regimens for concurrent systemic chemotherapy were FOLFIRI (40%) and FOLFOX (20%). Only one patient was chemotherapy naïve before HAIP. There was no statistically significant difference in 24-month OS between those who received HAIP with or without concurrent systemic chemotherapy (75.0% vs. 67.3%, p = 0.924).

3.6 Concurrent PTR

Most of the 28 pump placements were performed for CRLM (92.9%). Of these, 18 (69.2%) underwent concurrent PTR. One patient still has their primary tumor intact, four had metachronous CRLM with previously resected primary tumor, and two with synchronous CRLM underwent emergent PTR. OS from date of diagnosis was significantly worse for those who had concurrent PTR (27.4 months) compared with those who did not (69.7 months, p = 0.030). When those with metachronous CRLM were excluded, there was no statistically significant difference in OS (27.4 months vs. 58.3 months, p = 0.263). There was no statistically significant difference in PFS between these cohorts (6.9 months vs. 9.9 months, p = 0.460). There was no difference in OS from date of HAIP placement (20.5 months vs. 20.9 months, p = 0.996).

4 Discussion

This single-center series represents a real-world example of implementation of a HAIP program in a university-based standalone cancer hospital by expert surgeons who were previously trained in the technique. HAIP programs should be managed by a multidisciplinary team within a select expert center. Coordination is required between the surgeon, operating room staff, medical oncology, pharmacy, nursing and outpatient staff, nuclear medicine, and interventional radiology. Additionally, the surgical trainees and advanced practice providers must be familiar with potential short- and long-term complications of HAIP when these patients present in the emergency department. Various other administrative, financial, or institutional barriers may be encountered by centers attempting to start a HAIP program [19].

In prior years, HAIP therapy was offered at our institution. In a series published by Chakedis et al., 60 patients were treated between 2012 and 2016, with a higher proportion treated in the adjuvant setting (43%) [20]. Overall complication rate was similar at 32%, but there was a higher rate of overall pump complications (23%) and lower rate of biliary complications (2%) compared with our current series. Time to liver progression was similar at 9.2 months. Chakedis et al. also examined the influence of sarcopenia and showed it was associated with worse OS (HR 2.4, 95% CI 1.1–5.0) [20]. This surgeon-led program ended in 2016 and there were no HAIPs placed at our institution between 2017 and 2019. Therefore, the series reported herein is distinct from and independent of this older series, and represents implementation of a new HAIP program.

These data demonstrate that HAIP was technically successful in most patients with an acceptable complication rate. The rate of biliary sclerosis among those with CRLM was 23.1%, whereas prior series describe an incidence of approximately 5% for adjuvant HAIP and even lower for unresectable CRLM [21]. However, this higher rate is similar to other contemporary single-institution series [5]. Concurrent bevacizumab can increase the risk of biliary toxicity, but none of the patients in this series were on bevacizumab while receiving HAIP therapy [22]. It is interesting that 83.3% of those with biliary toxicity received bevacizumab before HAIP therapy compared with 66.7% of those without biliary toxicity, though this difference was not statistically significant. There were very few pump pocket or catheter-related complications [11]. Duration of therapy was similar compared to prior series [5, 20, 23]. The rate of complications did not impact oncologic outcomes.

Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic chemotherapy. In a recent systematic review and meta-analysis by Sugumar et al., landmark survival estimates for HAIP with systemic chemotherapy were as follows: 12-month OS 80%, 24-month OS 54%, 36-month OS 35% [24]. Landmark survival estimates were generally similar in our cohort, with 12-month OS of 87.4%, 24-month OS of 71.6%, and 36-month OS of 17.8%. The sharp decrease from 71.6% 24-month OS to 17.8% 36-month OS may be due to relatively short follow-up to date. Only one patient in our series was chemotherapy naïve before HAIP therapy. This represents a potential area for improvement in the HAIP program, as some data suggests a significant benefit of up-front HAIP with systemic chemotherapy in unresectable CRLM [23]. However, the adoption of this treatment is currently being explored through ECOG EA2222 trial [25].

One unique finding in these data is the significant difference in OS from date of diagnosis when comparing those who had concurrent PTR with those who did not. This finding should be interpreted with caution, as the inclusion of patients with metachronous CRLM introduces a source of immortal time bias [26] Nevertheless, the distinct difference in OS between those who had PTR and those who did not is intriguing and raises the issue of the utility of PTR. PTR in the setting of metastatic colorectal cancer remains controversial. Randomized trials demonstrate no survival benefit of PTR in metastatic colorectal cancer [27, 28] However, PTR is still recommended by National Comprehensive Cancer Network (NCCN) guidelines before consideration of liver-directed therapy for CRLM [29] Furthermore, concurrent PTR with HAIP placement is widely performed and considered safe [30]. In light of the level 1 data showing no survival benefit for PTR, a liver-focused approach could be recommended for patients with unresectable CRLM with an asymptomatic primary tumor.

To date, there is very limited level 1 data to guide optimal use of HAIP within the broader treatment paradigm for patients with CRLM. The only level 1 data for HAIP therapy is the CALGB 9481 trial which randomized patients to systemic 5-FU or hepatic arterial infusion of FUDR [31]. Since then, observational studies such as this have described real-world outcomes of HAIP after or in conjunction with modern chemotherapy, which typically involves multiagent 5-FU based chemotherapy with or without other agents such as bevacizumab, EGFR inhibitors, or immune checkpoint inhibitors. The highly anticipated EA2222 PUMP trial (NCT05863195) is currently enrolling and will evaluate the benefit of HAIP following 3–6 months of standard multiagent 5-FU-based systemic chemotherapy. Adjuvant HAIP is being studied in the Netherlands for low-risk colorectal liver metastasis [13].

Limitations of this study include the single center, small number of patients, lack of control or comparison group, and heterogeneity of treatment regimens. Therefore, this analysis is limited to a descriptive nature and broad conclusions cannot be drawn from these results. However, the real-world data presented herein are similar to those of surgeon-directed HAIP programs, and may be generalizable to other centers that are beginning a HAIP program [5, 20]. Another limitation is that this database only captured patients who underwent an operation with a plan for HAIP placement. Therefore, we do not know how many patients at our institution were evaluated and determined not to be candidates for HAIP, eligible but not referred for HAIP therapy, did not elect to undergo HAIP placement, or were treated with other local therapies aside from resection. These therapies can include stereotactic body radiotherapy, transarterial radioembolization, and transarterial chemoembolization [32].

5 Conclusions

HAIP therapy can be safely implemented at institutions with limited prior experience. Survival outcomes were similar to those reported in larger series. The relationship between PTR and liver-directed therapy in colorectal liver metastasis warrants further investigation.

Disclosure

The authors have nothing to report.

Ethics Statement

This study was approved by the Institutional Review Board at The Ohio State University under protocol #2023C0177. Informed consent was waived due to the retrospective nature of the study. The study was conducted in accordance with the ethical standards of the IRB at The Ohio State University and with the Helsinki Declaration of 1975, as revised in 1983.

Open Research

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

References

1 Cancer Facts & Figures 2024 (Atlanta: American Cancer Society, 2024).
Google Scholar
2E. K. Abdalla, J. N. Vauthey, L. M. Ellis, et al., “Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases,” Annals of Surgery 239, no. 6 (2004): 818–827, https://doi.org/10.1097/01.sla.0000128305.90650.71.
10.1097/01.sla.0000128305.90650.71
PubMed Web of Science® Google Scholar
3J. Datta, R. R. Narayan, N. E. Kemeny, and M. I. D'Angelica, “Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review,” JAMA Surgery 154, no. 8 (2019): 768–776, https://doi.org/10.1001/jamasurg.2019.1694.
10.1001/jamasurg.2019.1694
PubMed Google Scholar
4C. Charnsangavej, B. Clary, Y. Fong, A. Grothey, T. M. Pawlik, and M. A. Choti, “Selection of Patients for Resection of Hepatic Colorectal Metastases: Expert Consensus Statement,” Annals of Surgical Oncology 13, no. 10 (2006): 1261–1268, https://doi.org/10.1245/s10434-006-9023-y.
10.1245/s10434-006-9023-y
PubMed Web of Science® Google Scholar
5B. S. Walker, K. G. Billingsley, T. L. Sutton, et al., “Hepatic Arterial Infusion Pump Chemotherapy Combined With Systemic Therapy for Patients With Advanced Colorectal Liver Metastases: Outcomes in a Newly Established Program,” Journal of Surgical Oncology 126, no. 3 (2022): 513–522, https://doi.org/10.1002/jso.26911.
10.1002/jso.26911
CAS PubMed Web of Science® Google Scholar
6W. D. Ensminger, “Intrahepatic Arterial Infusion of Chemotherapy: Pharmacologic Principles,” Seminars in Oncology 29, no. 2 (2002): 119–125, https://doi.org/10.1053/sonc.2002.31679.
10.1053/sonc.2002.31679
CAS PubMed Web of Science® Google Scholar
7R. Anteby, N. E. Kemeny, P. T. Kingham, et al., “Getting Chemotherapy Directly to the Liver: The Historical Evolution of Hepatic Artery Chemotherapy,” Journal of the American College of Surgeons 232, no. 3 (2021): 332–338, https://doi.org/10.1016/j.jamcollsurg.2020.11.013.
10.1016/j.jamcollsurg.2020.11.013
PubMed Google Scholar
8N. Kemeny, Y. Huang, A. M. Cohen, et al., “Hepatic Arterial Infusion of Chemotherapy After Resection of Hepatic Metastases From Colorectal Cancer,” New England Journal of Medicine 30 341, no. 27 (1999): 2039–2048, https://doi.org/10.1056/NEJM199912303412702.
10.1056/NEJM199912303412702
CAS PubMed Web of Science® Google Scholar
9S. J. Judge, T. Ghalambor, M. J. Cavnar, et al., “Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network,” Annals of Surgical Oncology 30, no. 12 (2023): 7362–7370, https://doi.org/10.1245/s10434-023-14207-7.
10.1245/s10434-023-14207-7
PubMed Web of Science® Google Scholar
10M. I. D'Angelica, C. Correa-Gallego, P. B. Paty, et al., “Phase II Trial of Hepatic Artery Infusional and Systemic Chemotherapy for Patients With Unresectable Hepatic Metastases From Colorectal Cancer: Conversion to Resection and Long-Term Outcomes,” Annals of Surgery 261, no. 2 (2015): 353–360, https://doi.org/10.1097/SLA.0000000000000614.
10.1097/SLA.0000000000000614
PubMed Web of Science® Google Scholar
11J. M. Sharib, J. M. Creasy, B. Wildman-Tobriner, et al., “Hepatic Artery Infusion Pumps: A Surgical Toolkit for Intraoperative Decision-Making and Management of Hepatic Artery Infusion-Specific Complications,” Annals of Surgery 276, no. 6 (2022): 943–956, https://doi.org/10.1097/SLA.0000000000005434.
10.1097/SLA.0000000000005434
PubMed Google Scholar
12G. P. Wright, S. Perkins, H. Jones, et al., “Surgical Resection Does Not Improve Survival in Multifocal Intrahepatic Cholangiocarcinoma: A Comparison of Surgical Resection With Intra-Arterial Therapies,” Annals of Surgical Oncology 25, no. 1 (2018): 83–90, https://doi.org/10.1245/s10434-017-6110-1.
10.1245/s10434-017-6110-1
PubMed Google Scholar
13F. E. Buisman, M. Y. V. Homs, D. J. Grünhagen, et al., “Adjuvant Hepatic Arterial Infusion Pump Chemotherapy and Resection Versus Resection Alone in Patients With Low-Risk Resectable Colorectal Liver Metastases—The Multicenter Randomized Controlled Pump Trial,” BMC Cancer 19, no. 1 (2019): 327, https://doi.org/10.1186/s12885-019-5515-6.
10.1186/s12885-019-5515-6
CAS PubMed Web of Science® Google Scholar
14D. Goéré, J. P. Pignon, M. Gelli, et al., “Postoperative Hepatic Arterial Chemotherapy in High-Risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases—A Randomized Phase Ii/Iii Trial - Pacha-01 (Nct02494973),” BMC Cancer 18, no. 1 (2018): 787, https://doi.org/10.1186/s12885-018-4697-7.
10.1186/s12885-018-4697-7
PubMed Google Scholar
15A. Cercek, T. Boerner, B. R. Tan, et al., “Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial,” JAMA Oncology 6, no. 1 (2020): 60–67, https://doi.org/10.1001/jamaoncol.2019.3718.
10.1001/jamaoncol.2019.3718
PubMed Web of Science® Google Scholar
16E. A. Eisenhauer, P. Therasse, J. Bogaerts, et al., “New Response Evaluation Criteria in Solid Tumours: Revised Recist Guideline (Version 1.1),” European Journal of Cancer 45, no. 2 (2009): 228–247, https://doi.org/10.1016/j.ejca.2008.10.026.
10.1016/j.ejca.2008.10.026
CAS PubMed Web of Science® Google Scholar
17M. Qadan, M. I. D'Angelica, N. E. Kemeny, A. Cercek, and T. P. Kingham, “Robotic Hepatic Arterial Infusion Pump Placement,” HPB 19, no. 5 (2017): 429–435, https://doi.org/10.1016/j.hpb.2016.12.015.
10.1016/j.hpb.2016.12.015
PubMed Google Scholar
18Y. Fong, J. Fortner, R. L. Sun, M. F. Brennan, and L. H. Blumgart, “Clinical Score for Predicting Recurrence After Hepatic Resection for Metastatic Colorectal Cancer: Analysis of 1001 Consecutive Cases,” Annals of Surgery 230, no. 3 (1999): 309–318, https://doi.org/10.1097/00000658-199909000-00004.
10.1097/00000658-199909000-00004
CAS PubMed Web of Science® Google Scholar
19M. Cavnar, T. Ghalambor, M. E. Lidsky, et al., “Considerations and Barriers to Starting a New HAI Pump Program: An International Survey of the Hai Consortium Research Network,” HPB 24, no. 12 (2022): 2104–2111, https://doi.org/10.1016/j.hpb.2022.08.008.
10.1016/j.hpb.2022.08.008
PubMed Google Scholar
20J. Chakedis, E. W. Beal, S. Sun, et al., “Implementation and Early Outcomes for a Surgeon-Directed Hepatic Arterial Infusion Pump Program for Colorectal Liver Metastases,” Journal of Surgical Oncology 118, no. 7 (2018): 1065–1073, https://doi.org/10.1002/jso.25249.
10.1002/jso.25249
CAS PubMed Google Scholar
21K. Ito, H. Ito, N. E. Kemeny, et al., “Biliary Sclerosis After Hepatic Arterial Infusion Pump Chemotherapy for Patients With Colorectal Cancer Liver Metastasis: Incidence, Clinical Features, and Risk Factors,” Annals of Surgical Oncology 19, no. 5 (2012): 1609–1617, https://doi.org/10.1245/s10434-011-2102-8.
10.1245/s10434-011-2102-8
PubMed Web of Science® Google Scholar
22A. Cercek, M. D'Angelica, D. Power, et al., “Floxuridine Hepatic Arterial Infusion Associated Biliary Toxicity Is Increased by Concurrent Administration of Systemic Bevacizumab,” Annals of Surgical Oncology 21, no. 2 (2014): 479–486, https://doi.org/10.1245/s10434-013-3275-0.
10.1245/s10434-013-3275-0
PubMed Web of Science® Google Scholar
23F. S. Verheij, K. F. D. Kuhlmann, D. R. Silliman, et al., “Combined Hepatic Arterial Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients With Unresectable Colorectal Liver Metastases,” Annals of Surgical Oncology 30, no. 13 (2023): 7950–7959, https://doi.org/10.1245/s10434-023-14073-3.
10.1245/s10434-023-14073-3
PubMed Google Scholar
24K. Sugumar, H. Stitzel, V. Wu, et al., “Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-Analysis,” Annals of Surgical Oncology 31 (2024): 4413–4426, https://doi.org/10.1245/s10434-024-15187-y.
10.1245/s10434-024-15187-y
PubMed Google Scholar
25O. Standring and S. Gholami, “First-Line Hepatic Artery Infusion for Unresectable Clm Works, But Will We Ever Get There?” Annals of Surgical Oncology 30, no. 13 (2023): 7918–7920, https://doi.org/10.1245/s10434-023-14305-6.
10.1245/s10434-023-14305-6
PubMed Google Scholar
26K. Yadav and R. J. Lewis, “Immortal Time Bias in Observational Studies,” JAMA 325, no. 7 (2021): 686–687, https://doi.org/10.1001/jama.2020.9151.
10.1001/jama.2020.9151
PubMed Web of Science® Google Scholar
27Y. Kanemitsu, K. Shitara, J. Mizusawa, et al., “Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial,” Journal of Clinical Oncology 39, no. 10 (2021): 1098–1107, https://doi.org/10.1200/JCO.20.02447.
10.1200/JCO.20.02447
CAS PubMed Web of Science® Google Scholar
28N. N. Rahbari, S. Biondo, R. Frago, et al., “Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the Synchronous and CCRe-IV Trials,” Journal of Clinical Oncology 42, no. 13 (2024): 1531–1541, https://doi.org/10.1200/JCO.23.01540.
10.1200/JCO.23.01540
CAS PubMed Google Scholar
29 NCCN Guidelines Version 2, Colon Cancer (National Comprehensive Cancer Network, 2024). Accessed May 1, 2024, https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.
Google Scholar
30B. C. Brajcich, D. J. Bentrem, A. D. Yang, et al., “Short-Term Risk of Performing Concurrent Procedures With Hepatic Artery Infusion Pump Placement,” Annals of Surgical Oncology 27, no. 13 (2020): 5098–5106, https://doi.org/10.1245/s10434-020-08938-0.
10.1245/s10434-020-08938-0
PubMed Google Scholar
31N. E. Kemeny, D. Niedzwiecki, D. R. Hollis, et al., “Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481),” Journal of Clinical Oncology 24, no. 9 (2006): 1395–1403, https://doi.org/10.1200/JCO.2005.03.8166.
10.1200/JCO.2005.03.8166
CAS PubMed Web of Science® Google Scholar
32E. Filoni, V. Musci, A. Di Rito, R. Inchingolo, R. Memeo, and F. Mannavola, “Multimodal Management of Colorectal Liver Metastases: State of the Art,” Oncology Reviews 17 (2024): 11799, https://doi.org/10.3389/or.2023.11799.
10.3389/or.2023.11799
PubMed Google Scholar

Synopsis

Hepatic artery infusion pump (HAIP) therapy may be used to treat unresectable colorectal liver metastases but requires specialized centers with multidisciplinary coordination. Implementation of a HAIP program at a single center was done safely and with acceptable oncologic outcomes.

Volume131, Issue2

February 2025

Pages 212-219

Implementation of Hepatic Artery Infusion Pump Therapy: Real-World Single-Center Experience