Hepatic Arterial Infusion Therapy Research Articles

Safety and Effectiveness of Portal Vein Embolization after Hepatic Arterial Infusion Therapy

Portal vein embolization (PVE) is a potential tool useful for inducing future liver remnant (FLR) hypertrophy in patients with advanced hepatic malignancies who are at high risk of hepatic insufficiency if treated with surgical resection. However, the safety and effectiveness of PVE in the context of patients who have undergone hepatic arterial infusion (HAI) are unknown. This retrospective, single-center study identified 9 patients who underwent PVE after HAI between January 2015 and December 2022. There were no major adverse events, including biliary, or high-grade liver failure. Analysis showed an increase in standardized FLR from 21.1% (SEM ± 2.4) to 34.8% (SEM ± 2.1) over 9.8 weeks (SEM ± 1.2), with a mean kinetic growth rate of 1.9% (interquartile range, 0.9%–2.4%). This study suggested compatibility of PVE after HAI. Patients who have undergone HAI therapy should not be excluded from consideration of PVE as part of their operative clearance strategy.

Efficacy and Safety of Hepatic Arterial Infusion Therapy with Cinobufacini in Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Retrospective Cohort Study.

The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40-0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03-2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08-1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.

A phase II trial of induction systemic mFOLFIRINOX followed by hepatic arterial infusion of floxuridine and dexamethasone given concurrently with systemic mFOLFIRI as a first-line therapy in patients with unresectable liver-dominant intrahepatic cholangiocarcinoma (HELIX-1).

511 Background: Most patients with intrahepatic cholangiocarcinoma (ICC) have unresectable or multifocal liver-dominant disease. Survival after first-line systemic therapy remains poor, with median progression-free (mPFS) and overall survival of 7.2 and 12.8 months, respectively. Hepatic arterial infusion (HAI) therapy with floxuridine maximizes liver-specific treatment with minimal systemic toxicity and potentially offers improved disease control when combined with systemic therapy. Methods: HELIX-1 (NCT04251715) is an investigator-initiated, first-line, single-center, single-arm phase II clinical trial for patients with liver-dominant unresectable or multifocal ICC. The trial was designed with a patient safety run-in evaluating toxicity from the combined therapy. Pre-trial screening included laparoscopy, biopsies, and PET/CT. Eligible patients were treated with systemic mFOLFIRINOX for 4 cycles in order to select those likely to benefit from HAI. Patients with disease control on restaging proceeded to HAI pump placement and treatment with HAI floxuridine for 14 days followed by systemic mFOLFIRI on a 28-day cycle. The co-primary objectives were to assess safety of the combined therapeutic strategy and the disease control rate (DCR) at 6 months (RECIST v1.1) at end of trial (EOT). Results: A total of n=5 patients with liver-only ICC enrolled in the trial and completed the entire study protocol. The median age was 60 years (range 42-69) with a dominant lesion size of 9.8cm (range 8.4-14.5). All patients had both right and left hemiliver involvement with a median of 9 intrahepatic tumors (range 1-15). No patients experienced grade 3 or 4 adverse events, or hepatic dysfunction leading to cessation of HAI therapy. The DCR at 6 months was 100%, with a mPFS of 18.2 months. All five patients achieved partial radiographic response (PR) while receiving HAI therapy, and remain alive with liver-only disease at a median of 18.4 months (range 12.7-20) after study enrollment. After continuing treatment with HAI and systemic mFOLFIRI beyond the EOT, two patients transitioned to HAI treatment only and then to biochemical and radiographic surveillance without therapy after demonstrating PR and CA19-9 normalization. Conclusions: Integration of HAI floxuridine with mFOLFIRI following mFOLFIRINOX induction for patients with liver-only advanced ICC is well-tolerated and demonstrates longer DCR in comparison to historical controls. The combined regimen minimized systemic toxicity and allowed a large proportion of patients to transition to liver-only HAI treatment with maintained disease control. Future directions include combining HAI with new first-line systemic regimens for patients with advanced ICC. Clinical trial information: NCT04251715 .

Validation of a novel web-based application for hepatic arterial infusion floxuridine dosing.

15 Background: Hepatic arterial infusion (HAI) floxuridine (FUDR) dosing is a complex, multifactorial process with weight-based dosing dependent on the fold change of aspartate aminotransferase, alkaline phosphatase, and total bilirubin relative to reference values from preceding cycles and compounded over time. Given the complexity of dosing calculations and lack of experience with this treatment in community centers, HAI is typically administered only at tertiary oncology centers with limited access for rural disadvantaged patients. We developed an online tool to automate the dosing of FUDR to broaden safe and effective administration of HAI. Methods: The FUDR dosing algorithm developed at Memorial Sloan Kettering Cancer Center was digitalized as eDoseHAI, a novel multi-layer architecture web application tool featuring JavaScript (front-end), C# RESTful API (back-end) and Azure SQL server (data storage with Splunk data lake event registration). To validate this tool, manual dosing from patients who received ≥1 dose of HAI FUDR at our institution 6/2020-8/2023 was retrospectively compared to app-based dosing. Mismatch between app-based dosing and historical manual dosing was designated as dosing errors, excluding intentional adjustments based on physician discretion. Results: Internal validity was tested by entering records into eDoseHAI from 54 patients who received a total of 370 FUDR cycles (median 6; range 1-19). Ten patients (18.5%) were found to have unintentional dosing errors (e.g., delayed dose reductions) during treatment, impacting 52 cycles (14.1%). The median cycle at first error was 3 (range 2-6), impacting a median of 5 cycles (range 3-12). Dosing errors occurred in only 11.1% of the 45 patients supervised by a senior HAI physician, compared to 55.6% of the 9 patients supervised by three less experienced HAI physicians. Dosing accuracy improved over time; among the 14 patients on active HAI therapy, only 1 had an identified dosing error. eDoseHAI was able to reliably and accurately calculate dosing for all patients. Conclusions: HAI FUDR dosing is nuanced and complex, such that dosing errors occurred even with senior HAI oncologists. eDoseHAI is a web-based application tool designed to improve accuracy and thus safety of HAI dosing. We plan to further validate eDoseHAI using external data from an international HAI consortium, and to conduct a phase II clinical trial in which our team supervises FUDR dosing by community oncologists using eDoseHAI's supervisory mode with a goal to disseminate HAI therapy to disadvantaged rural patients who lack access.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5months (95% confidence interval [CI], 8.1-12.9) and 6.0months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p=0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p=0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p=0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p=0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p<0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

Combined Hepatic Arterial Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases.

Chemotherapy-naive patients with unresectable colorectal liver metastases (CRLM) have been the best responders to hepatic arterial infusion (HAI) therapy. The current treatment paradigm has drifted away from HAI in the first-line setting. We aimed to analyze outcomes of combined first-line systemic therapy with HAI therapy (HAI+SYS) in the modern era. We conducted a retrospective study of consecutive chemotherapy-naive patients with unresectable CRLM who received HAI+SYS between 2003 and 2019. Patients were selected from a prospectively maintained database. Outcomes included radiological response rate, conversion to resection (CTR) rate, and overall survival (OS). Fifty-eight chemotherapy-naive patients were identified out of 546 patients with unresectable CRLM managed with HAI. After induction treatment, 4 patients (7%) had a complete radiological response, including two durable responses. In total, 32 patients (55%) underwent CTR. CTR or complete response without resection was achieved after seven cycles of systemic therapy and four cycles of HAI therapy. Median OS for the whole cohort was 53.0 months (95% confidence interval 23.0-82.9). Three- and 5-year OS in patients who achieved CTR or complete response versus patients who did not was 88% and 72% versus 27% and 0% respectively. Of patients who underwent CTR, complete and major pathological response (no and <10% viable tumor cells, respectively) was observed in 7 (22%) and 12 patients (38%). Combined HAI+SYS in chemotherapy-naive patients resulted in durable and substantial response in a large proportion of patients. Nearly two-thirds of patients achieved a complete response or proceeded to conversion surgery, which was associated with prolonged survival.

Stage IV Rectal Cancer and Timing of Surgical Approach

AbstractLiver metastases are seen in at least 60% of patients with colorectal cancer at some point during the course of their disease. The management of both primary and liver disease is uniquely challenging in rectal cancer due to competing treatments and complex sequence of treatments depending on the clinical presentation of disease. Recently, several novel concepts are shaping new treatment paradigms, including changes in timing, sequence, and duration of therapies combined with potential deescalation of treatment components. Overall, the treatment of this clinical scenario mandates multidisciplinary evaluation and personalization of care; however, there is still considerable debate regarding the timing of liver metastasectomy in the context of the overall treatment plan. Herein, we will discuss the current literature on management of rectal cancer with synchronous liver metastasis, current treatment approaches with respect to chemotherapy, and role of hepatic artery infusion therapy.

American Radium Society Appropriate Use Criteria for the use of liver-directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines.

The liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.

Surgery and hepatic artery infusion therapy for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma is an aggressive tumor that commonly presents at an advanced stage requiring multimodal treatment. Surgical resection remains the only curative option; however, only 20% to 30% of patients present with resectable disease as these tumors remain asymptomatic at an early stage. Diagnostic workup for intrahepatic cholangiocarcinoma includes contrast-enhanced cross-sectional imaging (eg, computed tomography, magnetic resonance imaging) to determine resectability and percutaneous biopsy for patients receiving neoadjuvant therapy or with unresectable disease. Surgical treatment of resectable intrahepatic cholangiocarcinoma is centered on complete resection of the mass with negative (R0) margins while preserving sufficient future liver remnant. Intraoperative measures that aid in ensuring resectability include diagnostic laparoscopy to rule out peritoneal disease or distant metastases and ultrasound to evaluate for vascular invasion or intrahepatic metastases. Predictors of survival after surgery for intrahepatic cholangiocarcinoma include margin status, vascular invasion, nodal disease, and tumor size and multifocality. Patients with resectable intrahepatic cholangiocarcinoma may also benefit from systemic chemotherapy in either the neoadjuvant or adjuvant setting; however, guidelines do not presently support the use of neoadjuvant chemotherapy outside of ongoing clinical trials. For unresectable intrahepatic cholangiocarcinoma, the combination of gemcitabine and cisplatin has been the first-line chemotherapeutic option, but recent advancements in triplet regimens and immunotherapies may offer novel strategies. Hepatic artery infusion presents an efficacious adjunct to systemic chemotherapy as it takes advantage of the hepatic arterial blood supply that feeds intrahepatic cholangiocarcinomas to deliver high-dose chemotherapy to the liver through a subcutaneous pump. Thus, hepatic artery infusion takes advantage of first-pass hepatic metabolism and provides liver-directed therapy while minimizing systemic exposure. In unresectable intrahepatic cholangiocarcinoma, using hepatic artery infusion therapy in conjunction with systemic chemotherapy has been associated with better overall survival and response rates when compared to systemic chemotherapy alone or other liver-directed therapies, such as transarterial chemoembolization and transarterial radioembolization. This review focuses on surgical intervention for resectable intrahepatic cholangiocarcinoma and the utility of hepatic artery infusion for patients with unresectable disease.

Update on Cholangiocarcinoma

AbstractCholangiocarcinoma remains a challenge both in terms of diagnosis and treatment. Due to the lack of a useful screening test and often clinically silent early course, disease stage is often advanced at the time of diagnosis. Surgical resection remains the only potentially curative treatment option and recurrence rates are high; however, liver transplantation has recently resulted in promising outcomes in certain groups of patients with intrahepatic and perihilar cholangiocarcinoma. For patients in whom surgery is not an option, chemotherapy with gemcitabine and cisplatin is the first-line treatment. An array of locoregional management options exists, which includes transarterial embolization, hepatic arterial chemotherapy infusion, ablation, and radiation therapy. High-quality data from randomized controlled trials for these treatments remains limited, however, and additional study is needed.

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.

Perioperative and oncologic outcomes of hepatic artery infusion pump therapy at an expanding HAI program.

120 Background: Hepatic artery infusion (HAI) is a liver directed therapy to treat unresectable or resected colorectal liver metastases (CRLM) and unresectable intrahepatic cholangiocarcinoma (ICC). Historically, HAI has only been performed at few specialized centers; however, there is increasing expansion to new centers. We previously reported safety outcomes of our index year of HAI therapy. We now report safety, feasibility, efficacy and oncologic outcomes for an expanded cohort of 62 patients in an established HAI program. Methods: Patients selected for HAI by multidisciplinary review were evaluated for demographics and perioperative outcomes. Objective hepatic response was calculated according to RECIST 1.1. Overall, hepatic and extrahepatic progression-free survival (PFS) were calculated by the Kaplan-Meier method on an intent-to-treat basis. Results: 62 patients were treated with HAI from November 2018-September 2021: 46 for unresectable CRLM, 8 as adjuvant HAI for resected CRLM, and 8 for unresectable ICC. Median age was 54.5 years (range 32-80), 58% were male, and 97% received prior chemotherapy (median 12 cycles, range 0-66). Hepatectomy (18, 29%) and/or colectomy/proctectomy (27, 43.5%) was performed concurrently with pump placement, and 19 (30.6%) were performed robotically. Median operating time was 265 minutes (range 130-526), estimated blood loss was 100 mL (range 22-1000) and length of stay was 5 days (range 1-19). HAI-specific complications occurred in 14% (Table). Floxuridine (FUDR) was initiated in 95% of patients a median of 18.5 days after surgery. Of the 38 patients who received HAI for unresectable CRLM and had measurable disease on imaging, 3- and 6-month hepatic disease control was achieved in 86% (8 partial response [PR], 22 stable disease [SD], 5 progressed [PD]) and 89% (1 complete response, 8 PR, 8 SD, 2 PD), respectively. For patients with at least 3 months follow-up, median PFS, hepatic PFS and extrahepatic PFS were 13 months, 13 months, and 13 months, respectively. Conclusions: HAI can be safely and effectively delivered to well-selected patients with CRLM and ICC. Response rates, disease control and PFS in heavily treated patients with unresectable CRLM comparable to high-volume centers can be achieved at new programs with appropriate expertise. These data support the mission of the newly formed HAI Consortium to critically evaluate efficacy and innovation in HAI therapy through multi-institutional collaboration and contemporary prospective trials.[Table: see text]

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

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

Building a Successful Hepatic Artery Infusion (HAI) Program: An International Survey of the HAI Consortium Research Network

Introduction: Despite encouraging oncologic outcomes, widespread implementation of hepatic arterial infusion (HAI) therapy has faced multiple barriers. By querying members of the recently established international HAI Consortium Research Network (HCRN), this survey aims to identify important elements and challenges in establishing a successful HAI program. Methods: Using SurveyMonkey™, a 17-question survey assessing perceived factors required for establishing a successful program was developed by 12 HCRN surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. For rank-order questions, scores were generated by calculating average ranking for each answer choice. Results: Twenty-eight HCRN surgical oncologists responded to the survey (figure). Implementation time varied, with 53.8% requiring less than a year, and up to 3 years for the rest. Most programs (n=17, 60.7%) became active in the past 5 years (32.1% from 2016-2018 and 28.6% from 2019-2021). Team members from 51% of new programs participated in on-site training at a high-volume center. Medical and surgical oncology were ranked most important for building a program (average rank scores 7.96 and 6.59/8, respectively). Half of the institutions required administrative or regulatory approval. Top 3 challenges faced when building a program were related to regulatory approval, device/equipment access, and drug (FUDR) access (average rank scores 6.65, 6.33, and 6.25/9, respectively). Conclusion: Widespread development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs and execution of multi-center clinical trials in HAI.

Celsite T202F B. Braun Catheter with Synchromed II Medtronic Pump for Hepatic Artery Infusion Therapy Is a Safe Alternative to Codman Pump Discontinuation: The First Latin-American HAIP Program Early Experience

Celsite T202F B. Braun Catheter with Synchromed II Medtronic Pump for Hepatic Artery Infusion Therapy Is a Safe Alternative to Codman Pump Discontinuation: The First Latin-American HAIP Program Early Experience

Combined Primary Resection with Hepatic Artery Infusion Pump Implantation Is Safe for Unresectable Colorectal Liver Metastases

BackgroundColorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established. MethodsPatients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics. ResultsPatients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS). ConclusionCombining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing.

Genomic Stratification of Resectable Colorectal Liver Metastasis Patients and Implications for Adjuvant Therapy and Survival.

To determine whether genomic risk groups identified by somatic mutation testing of colorectal liver metastasis (CRLM) can be used for "molecularly-guided" selection for adjuvant systemic chemotherapy and hepatic artery infusion of FUDR (SYS+HAI-FUDR). Several genomic biomarkers have been associated with clinical phenotype and survival for patients with resectable CRLM. It is unknown whether prognostication afforded by genomic stratification translates into enhanced patient selection for adjuvant hepatic artery infusion therapy. Consecutive patients with resected CRLM and available mutational characterization via Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets were reviewed from a prospective institutional database. Patients were stratified into three genomic risk groups based on previously defined alterations in SMAD4, EGFR and the RAS/RAF pathway. The association between SYS+HAI-FUDR and overall survival, relative to adjuvant chemotherapy alone (SYS), was evaluated in each genomic risk group by Cox proportional hazard regression and propensity score matched analyses. A total of 334 patients (SYS+HAI-FUDR 204; SYS 130) were identified; the rates of RAS/RAF alterations and SMAD4 inactivation were 47.4% and 11.7%, respectively. After a median follow-up of 58 months, adjuvant SYS+HAI-FUDR was independently associated with a reduced risk of death (HR 0.50, 95%CI 0.26-0.98, P = 0.045) in the low-risk genomic group, but not in the moderate-risk (HR 1.07, 95%CI 0.5-2.07, P = 0.749) or high-risk (HR 1.62, 95%CI 0.29-9.12, P = 0.537) cohorts. Following propensity score matching, adjuvant SYS+HAI-FUDR remained associated with significant improvements in long-term survival selectively in the low-risk genomic cohort (5-year actuarial survival: 89% vs. 68%, P = 0.019). Genomic alterations in RAS/RAF, SMAD4, and EGFR may be useful to guide treatment selection in resectable CRLM patients and warrant external validation and integration in future clinical trial design.

Circulating Hybrid Cells: A Novel Liquid Biomarker of Treatment Response in Gastrointestinal Cancers.

Real-time monitoring of treatment response with a liquid biomarker has potential to inform treatment decisions for patients with rectal adenocarcinoma (RAC), esophageal adenocarcinoma (EAC), and colorectal liver metastasis (CRLM). Circulating hybrid cells (CHCs), which have both immune and tumor cell phenotypes, are detectable in the peripheral blood of patients with gastrointestinal cancers, but their potential as an indicator of treatment response is unexplored. Peripheral blood specimens were collected from RAC and EAC patients after neoadjuvant therapy (NAT) or longitudinally during therapy and evaluated for CHC levels by immunostaining. Receiver operating characteristics (ROCs) and the Kaplan-Meier method were used to analyze the CHC level as a predictor of pathologic response to NAT and disease-specific survival (DSS), respectively. Patients with RAC (n=23) and EAC (n=34) were sampled on the day of resection, and 11 patients (32%) demonstrated a pathologic complete response (pCR) to NAT. On ROC analysis, CHC levels successfully discriminated pCR from non-pCR with an area under the curve of 0.82 (95% confidence interval [CI], 0.71-0.92; P<0.001). Additionally, CHC levels in the EAC patients correlated with residual nodal involvement (P=0.026) and 1-year DSS (P=0.029). The patients with RAC who were followed longitudinally during NAT (n=2) and hepatic arterial infusion therapy for CRLM (n=2) had CHC levels that decreased with therapy response and increased before clinical evidence of disease progression. Circulating hybrid cells are a novel blood-based biomarker with potential for monitoring treatment response and disease progression to help guide decisions for further systemic therapy, definitive resection, and post-therapy surveillance. Additional validation studies of CHCs are warranted.

Hepatic Arterial Infusion Pumps: What the Radiologist Needs to Know.

Hepatic arterial infusion (HAI) entails the surgical implantation of a subcutaneous pump to deliver chemotherapeutic agents directly to the liver in the setting of primary or secondary liver cancer. The purpose of HAI chemotherapy is to maximize hepatic drug concentrations while minimizing systemic toxicity, facilitating more effective treatment. HAI is used in combination with systemic chemotherapy and can be considered in several clinical scenarios, including adjuvant therapy, conversion of unresectable disease to resectable disease, and unresectable disease. Radiologists are key members of the multidisciplinary team involved in the selection and management of these patients with complex liver disease. As these devices begin to be used at more sites across the country, radiologists should become familiar with the guiding principles behind pump placement, expected imaging appearances of these devices, and potential associated complications. The authors provide an overview of HAI therapy, with a focus on the key imaging findings associated with this treatment that radiologists may encounter. ©RSNA, 2021.