Retrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors

Retrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Retrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors Allante Milsap, Matthew Sawyer, Syed Kazmi, Radhika Kainthla, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7255848/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose Hepatic arterial infusion pump (HAIP) therapy is a promising treatment for metastatic colorectal cancer (mCRC) with liver metastases, delivering targeted therapy to improve efficacy and reduce systemic toxicity. This retrospective study evaluates HAIP outcomes at an academic center and safety net hospital. Methods Patients with mCRC and liver metastases receiving at least one HAIP floxuridine (FUDR) cycle from 2013 to 2023 were included. Baseline data on demographics, tumor characteristics, and prior treatments were collected. The primary outcome was overall survival (OS) post-pump placement, with secondary outcomes of real-world progression-free survival (rwPFS) and HAIP-related complications. Results Of 88 patients assessed, 63 met inclusion criteria. Median age was 46 years (IQR 41–57); 54% were male. Prior to HAIP, 60% (n = 38) received one line of systemic therapy, and 29% (n = 18) received two. Median OS was 38.0 months (95% CI 21.9–not reached), and median rwPFS was 11.2 months (95% CI 7.1–16.1). Univariate analysis linked baseline bilirubin, KRAS mutation, and CEA levels to OS. However, only elevated baseline bilirubin remained an independent predictor of worse survival in the final multivariate model. Common complications were hematoma (6.4%, n = 4) and pump infection (3.2%, n = 2). Grade 3 FUDR toxicities were rare: elevated alkaline phosphatase (n = 6), AST/ALT (n = 3), bilirubin (n = 2), and thrombocytopenia (n = 1). Conclusions HAIP treatment with FUDR is an effective treatment option for patients with mCRC and hepatic metastasis. HAIP treatment is associated with enhanced survival outcomes and limited rates of complications. Prospective, randomized studies are needed to confirm HAIP's role in mCRC management. Hepatic Arterial Infusion Pump (HAIP) Colorectal Liver Metastasis Floxuridine Overall Survival Prognostic Factors Locoregional Therapy Figures Figure 1 Figure 2 Figure 3 Introduction Colorectal cancer (CRC) ranks as the third most diagnosed cancer in the United States, while standing as the second leading cause of cancer mortality.[ 1 ] Metastasis is detected in nearly a quarter of initial diagnoses of CRC, and ultimately develops in over half of patients overall [ 1 ]. Liver metastasis occurs in 70% of mCRC cases and is a primary driver of CRC-related mortality [ 2 ]. While surgical resection of colorectal liver metastasis (CRLM) is a potentially curative treatment option, only 10–20% of patients are eligible for this approach [ 3 ]. Of those who undergo resection of their CRLM, roughly half patients will develop recurrence within two years [ 4 ]. Therefore, it is imperative to explore alternative treatment strategies for CRLM. Hepatic arterial infusion (HAI) therapy is a vital locoregional treatment for patients with unresectable or recurrent CRLM. This approach leverages the liver's dual blood supply, where hepatic metastases are primarily perfused by the hepatic artery, while the normal liver parenchyma relies mostly on the portal vein. By delivering chemotherapy directly into the hepatic artery, HAI exploits the first-pass effect, where the liver extracts a high percentage of the drug before it reaches systemic circulation. [ 5 ] This results in significantly higher drug concentrations at the tumor site while reducing systemic toxicity. Floxuridine (FUDR) is particularly effective for HAI due to its short half-life and ~ 95% hepatic extraction rate, achieving local drug concentrations 100- to 400-fold higher than those possible with standard intravenous administration.[ 6 ] Surgical implantation of a hepatic arterial infusion pump (HAIP) creates a safe and effective outpatient platform for continuous chemotherapy infusion over extended periods. Clinical evidence supports HAIP’s efficacy in improving outcomes for patients with CRLM, particularly in those with resected oligometastatic disease. Among these patients, the addition of HAIP-FUDR to SCT significantly enhances recurrence-free survival, liver recurrence-free survival, and overall survival (OS) compared SCT alone. [ 7 – 11 ] A meta-analysis of ten randomized controlled trials further demonstrated a superior tumor response rate with HAIP (43% vs. 18%; relative risk: 2.26; p < 0.001). [ 12 ] In unresectable disease, HAIP’s efficacy is less established, though some studies report improved survival. [ 13 , 14 ]. Despite these encouraging findings, HAIP therapy remains restricted to specialized centers due to the multidisciplinary expertise required for its safe and effective implementation [ 6 ]. The broader adoption of HAIP is also hindered by persistent evidence gaps regarding optimal patient selection, outcomes in varied patient populations, and the lack of standardized treatment protocols. To address these challenges, this retrospective study evaluated the safety and efficacy of HAIP combined with SCT in patients with unresectable CRLM at an academic medical center and an affiliated safety-net hospital. The study assessed OS, progression-free survival (PFS), treatment-related complications, and potential prognostic factors in a diverse cohort, including recipients of both first-line and subsequent-line HAIP therapy. By examining real-world outcomes, this analysis aims to inform patient selection criteria, enhance the integration of HAIP into clinical practice, and underscore the need for prospective trials to establish standardized protocols for its use in unresectable CRLM. Methods Patients Candidate patients were identified by querying pharmacy records to identify patients who had received hepatic arterial infusion chemotherapy from either Parkland Memorial Hospital or Clements University Hospital in Dallas, Texas from 2013 to 2023. Patients were eligible for inclusion if they had a diagnosis of colon or rectal cancer and received at least one cycle of HAI-FUDR. Patients who had progressed prior to chemotherapy administration or those who had alternative primary malignancies were not eligible for analysis. Baseline covariates were collected from prior to HAI pump placement via chart review. These covariates include site of care (county hospital versus university hospital), demographics (age, gender, race, ethnicity), tumor characteristics (primary colon site, stage, KRAS and BRAF mutation status, mismatch repair status, size and number of liver metastases), baseline laboratory values (carcinoembryonic antigen, white blood cell count, hemoglobin, platelet count, total bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) and treatment data (types and number of chemotherapy lines received prior to HAI placement). Baseline covariates were extracted by the authors (M.S. and A.M.). Outcomes The primary outcome of interest was overall survival from date of pump placement. Secondary outcomes of interest included PFS, a composite of progression or death, as assessed by records from the treating physician or from imaging reports confirming progression. Time-to-event outcomes were analyzed using the Kaplan Meier method with an index date of hepatic arterial infusion pump placement until date of outcome of interest. Patients who had not met the outcome of interest were censored at the date of last clinical contact where vital status could be ascertained. To identify covariates associated with outcomes, multivariate Cox regression models were constructed following Collett’s four-step hybrid approach to model building. Briefly, all baseline covariates were analyzed in a univariate model. Those with a significance level of p ≤ 0.1 were analyzed in a multivariate model. Covariates were individually eliminated until a final model was reached in which all covariates met a significance of p ≤ 0.05. Eliminated models were then tested one-by-one and were retained if p ≤ 0.05. The final model was evaluated for goodness of fit using Cox Snell residuals, Akaike information criterion (AIC), and Bayesian information criterion (BIC). All statistical analyses were performed using Stata v18.0 (College Station, TX). Oversight This study was reviewed by the Institutional Review Board of the University of Texas Southwestern Medical Center and granted a waiver of consent. Results Patient Characteristics From 88 patients evaluated, 63 met inclusion criteria for this analysis, with the majority (n = 47, 75%) treated at the University site (Fig. 1 ). The median age at inclusion was 46 years (Interquartile Range [IQR] 41–57), and just over half of the patients were male (n = 34, 54%). Of the patients included, 48 (76%) had greater than 11 hepatic metastases. Primary tumors were predominantly left-sided, originating in the descending/sigmoid colon or rectum (n = 43, 68%). The median size of the largest lesion was 3.0 cm (IQR 2.1-6.0). Tumor stage T3 (n = 34, 54%) and nodal stage N2 (n = 26, 41%) were frequently observed. Prior to HAIP placement, 29 (44%) patients had received resection of their primary CRC, while 35 (56%) patients had their CRC resected concurrently with HAIP placement. Most patients had received prior systemic therapy, commonly one (n = 38, 60%) or two (n = 18, 29%) lines before HAIP initiation. Further baseline characteristics are detailed in Table 1 and Supplemental Table 1. Variable Total, n 63 Sites, n (%) UT Southwestern Medical Center 47 (75%) Parkland Memorial Hospital 16 (25%) Age, median (IQR) 46 (41–57) Gender, n (%) Male 34 (54%) Race, n (%) White 50 (79%) Black 6 (10%) Asian 3 ( 5%) Unknown 4 ( 6%) Ethnicity, n (%) Hispanic 16 (25%) Non-Hispanic 41 (65%) Decline/Unknown 6 (10%) Primary Tumor Site, n (%) Ascending Colon 13 (21%) Transverse Colon 7 (11%) Descending Colon or Sigmoid 32 (51%) Rectum 11 (17%) Primary tumor stage, n (%) T1 1 ( 2%) T2 5 ( 8%) T3 34 (54%) T4 6 (10%) T4a 8 (13%) T4b 6 (10%) Missing 3 ( 5%) N0 10 (16%) N1 4 ( 6%) N1a 5 ( 8%) N1b 11 (17%) N1c 3 ( 5%) N2 10 (16%) N2a 13 (21%) N2b 3 ( 5%) Missing 4 ( 6%) KRAS Mutation, (%) No 31 (49%) Yes 31 (49%) Missing 1 ( 2%) BRAF Mutation, n (%) No 60 (95%) Yes 2 ( 3%) Missing 1 ( 2%) Mismatch Repair Deficient, n (%) 0 ( 0%) Largest Liver Metastasis, median (I 3 cm (2.1-6) Number of Liver Metastases, n (%) Unknown 1 ( 2%) 1–4 7 (11%) 5–10 5 ( 8%) ≥11 48 (76%) Missing 2 ( 3%) Primary CRC resection, n (%) During HAIP placement 35, (56%) Prior to HAIP placement 29, (44%) Number of Chemocycles Prior to HAIP, median 8 Days to Initiation of HAIP chemotherapy, median 27* HAIP Chemotherapy provided, n (%) FUDR 63 (100%) Systemic therapy during HAIP treatment, n (%) FOLFOX-based 30 (48%) FOLFIRI-based 12 (19%) FOLFOXIRI-based 9 (14.3%) Other 12 (18.8%) *missing n = 3 Table 1. Baseline Patient and Tumor Characteristics. Summary of demographic, clinical, molecular, metastatic disease, and treatment characteristics for the study cohort (n = 63) at baseline. IQR, interquartile range; n, number Survival The median overall survival from the time of HAIP placement was 38.0 months (95% CI 21.9-NR) and median PFS was 11.2 months (95% CI 7.1–16.1) (Figs. 2 and 3). Kaplan-Meier overall survival is depicted in Fig. 2 . Baseline bilirubin, KRAS mutant status, and CEA were associated with OS in the univariate Cox model (Fig. 4, Table 2 ). However, the attempt to build a multivariate model was unsuccessful as the only significant covariate was baseline bilirubin (Table 3 ). KRAS mutation was retained in the multivariate model due to significant a priori belief on impact on outcomes. Table 2 Univariate Predictors of Overall Survival (OS). Results from univariate Cox proportional hazards regression analysis. Baseline total bilirubin (HR 6.86, 95% CI 1.42–33.13, p = 0.02), KRAS mutant status (ref = no; HR 3.7, 95% CI 1.09–12.53, p = 0.035), and baseline CEA (HR 0.94, 95% CI 0.90-1.00, p = 0.037) were identified as significant predictors of OS Univariate Cox OS HR 95% CI P Baseline Total Bilirubin ( per mg/dL) 6.86 1.42–33.13 0.02 KRAS Mutant (ref = no) 3.7 1.09–12.53 0.035 Baseline CEA 0.94 0.90-1.00 0.037 Table 3 Multivariate Predictors of Overall Survival (OS). Results from multivariate Cox proportional hazards regression analysis. After adjusting for covariates, baseline total bilirubin remained an independent predictor of overall survival (HR 3.87, 95% CI 1.20-12.44, p = 0.02), whereas KRAS mutant status (ref = no) was no longer statistically significant (HR 1.47, 95% CI 0.76–2.86, p = 0.25) Multivariate Cox OS HR 95% CI P Baseline Total Bilirubin ( per mg/dL) 3.87 1.20-12.44 0.02 KRAS Mutant (ref = no) 1.47 0.76–2.86 0.25 Toxicity Acute complications specifically related to the HAIP pump placement occurred in 11 patients (17.5%). The most common of these acute events were pump-site hematoma, observed in 4 patients (6.4%), and pump infection, occurring in 2 patients (3.2%). Several less frequent complications were noted, each occurring in a single patient (1.6% each): ventral hernia, post-operative abdominal pain requiring assessment, pump tip migration, evidence of extrahepatic perfusion, and the need for pump replacement (Table 4 ). Grade 3 toxicities from FUDR infusion were infrequent, involving alkaline phosphatase (n = 6), AST or ALT elevation (n = 3), bilirubin increase (n = 2), and platelet count decrease (n = 1) (Table 4 ). Table 4 HAIP-Related Complications and Toxicities. Acute complications from HAIP pump placement occurred in 17.46% of patients (n = 11), most commonly hematoma (6.35%) and pump site infection (3.17%). Chemotherapy-related laboratory toxicities are stratified by the highest severity grade, with liver function test elevations (Alk Phos, AST, ALT) being the most frequent abnormalities observed. Grade 3 bilirubin elevation occurred in two patients and Grade 3 decrease in platelets occurred in one patient Acute pump related complications, n (%) 11 (17.46%) Hematoma 4 (6.35%) Pump Infection 2 (3.17%) Ventral Hernia 1 (1.59%) Abdominal Pain 1 (1.59%) Pump Tip Migration 1 (1.59%) Extrahepatic Perfusion 1 (1.59%) Pump Replacement 1 (1.59%) HAIP Laboratory Toxicities, by Grade Grade 1, n Grade 2, n Grade 3, n Total, n Alk Phos Elevation 13 10 6 29 AST Elevation 5 9 3 17 ALT Elevation 6 7 3 16 Increase in Bilirubin 0 0 2 2 Decrease in Platelet 0 0 1 1 Discussion This retrospective analysis evaluated the efficacy and safety of HAIP chemotherapy combined with SCT in 63 patients with unresectable CRLM. The primary efficacy end points were a median OS of 38.0 months (95% CI 21.9–NR) and a median PFS of 11.2 months (95% CI 7.1–16.1). Notably, these survival outcomes were achieved in a heavily pre-treated population with a high disease burden, in which 76% of patients presented with 11 or more liver metastases and 40% had received prior SCT. Our analysis also identified baseline total bilirubin as the sole independent predictor of OS (HR 3.87; 95% CI 1.20–12.44; p = 0.02). HAIP treatment was associated with a manageable safety profile; acute pump-related complications occurred in 17.5% of patients, with a modest incidence of Grade 3 toxicities related to FUDR infusion. The results of this analysis suggest that HAIP with SCT is a safe and effective locoregional approach for this patient population. The median OS of 38.0 months achieved in our cohort falls within the upper range of 33–38 months reported in similar investigations among cohorts treated with HAIP and SCT [ 15 – 17 ]. This result is particularly significant when contrasted with outcomes from modern SCT alone. For instance, the TRIBE trial reported a median OS of 29.8 months with first-line FOLFOXIRI plus bevacizumab regimen, and a median OS of 25.8 months in the FOLFIRI plus bevacizumab group [ 18 ]. Similarly, the FIRE-3 trial, which compared first-line FOLFIRI plus either cetuximab or bevacizumab, demonstrated a median OS of 28.7 months in the cetuximab group and 25.0 months in the bevacizumab group.[ 19 ] Notably, our 38.0-month survival surpassed these benchmarks even though 40% of our patients had prior exposure to SCT, which contrasts sharply with the exclusively chemotherapy-naïve populations enrolled in TRIBE and FIRE-3. The true magnitude of this survival advantage is best illustrated in a direct comparison of chemotherapy-naïve patients, where adding HAIP to SCT has been shown to elevate the median OS to 53 months. [ 20 ] A key finding from this analysis was that baseline total bilirubin emerged as the sole statistically significant, independent predictor of overall survival, conferring a nearly four-fold increase in the risk of death (HR 3.87). Our observation aligns with other investigations that have established elevated bilirubin as a negative prognostic indicator for survival in CRLM.[ 21 , 22 ] Baseline bilirubin serves as a direct surrogate for hepatic reserve; higher levels indicate a compromised liver less able to tolerate the well-documented biliary toxicity of HAIP chemotherapy [ 11 , 23 , 24 ]. This treatment-related toxicity can manifest as further bilirubin elevation and, in severe cases, biliary sclerosis [ 25 ]. Consequently, patients with higher baseline bilirubin face increased risks of dose-limiting toxicities and treatment interruptions, adversely impacting survival. The clinical relevance of this principle is now validated by the eligibility criteria of major clinical trials, such as the active phase III EA2222/PUMP study, which mandates a strict baseline total bilirubin cutoff of ≤ 1.5 mg/dL.[ 26 ] Our data support using baseline bilirubin for risk stratification and suggest that HAIP therapy may be most beneficial when initiated earlier in the disease course, before the onset of significant liver dysfunction or extensive biliary involvement. In our cohort, KRAS mutations were associated with worse OS in univariate analysis (HR 3.7, p = 0.035), though this did not retain statistical significance after adjusting for bilirubin (HR 1.47, p = 0.25). This trend aligns with established KRAS-driven tumor biology: activating mutations in KRAS—present in 40–50% of colorectal cancers (CRCs)—constitutively activate MAPK signaling through impaired GTP hydrolysis and sustained GTP-bound states, promoting aggressive phenotypes including enhanced metastatic potential and metabolic reprogramming such as the Warburg effect.[ 27 ] KRAS-mutant tumors exhibit intrinsic chemoresistance through multiple mechanisms: (1) upregulation of drug efflux pumps (e.g., ABCB1/MDR1), (2) anti-apoptotic BCL-2 overexpression, and (3) creation of an immunosuppressive tumor microenvironment via PD-L1 induction and T-cell exclusion.[ 27 ] These properties may compromise HAIP efficacy, as the cytotoxic agent floxuridine (FUDR) relies on cellular uptake and apoptosis induction. Clinically, KRAS mutations correlate with reduced OS after liver metastasis resection and increased extrahepatic recurrence.[ 28 ] Notably, while KRAS mutations impair response to anti-EGFR agents, the HAIP/SCT regimen did not include EGFR inhibitors. The attenuated hazard ratio (HR) for KRAS-mutant tumors in multivariate analysis suggests bilirubin—a marker of hepatic dysfunction—may be a stronger pharmacokinetic determinant than KRAS status. However, the persistent directional trend toward worse outcomes in KRAS-mutant subgroups warrants further study, especially given KRAS's role in liver and lung metastasis tropism via mechanisms like TGF-β pathway activation [ 29 ] and chromosomal imbalances (e.g., KRAS amplification in brain metastases).[ 30 ] Evaluation of patient candidacy for HAIP therapy warrants careful consideration of its potential benefits against its risks. Early methods of chemotherapy administration via hepatic arterial infusion (HAI) were associated with significant adverse events, such as severe gastrointestinal toxicity (46%) and hepatic enzyme abnormalities (71%).[ 31 ] Contemporary HAIP, however, demonstrates a substantially improved safety profile given advances in pump devices, surgical techniques, and chemotherapy regimens [ 32 ]. Our data supports this improvement, showing an overall grade 3 toxicity rate of 9.52% (Table 4 ). In our cohort, procedure-related complications included hematoma (6.35%) and pump-site infection (3.17%). Pump-related issues, such as seroma formation, and catheter-related complications like malposition and extravasation also occurred, highlighting the need for meticulous surgical technique and careful post-procedural monitoring. While the incidence of hepatic toxicities, such as chemical hepatitis and biliary sclerosis, has decreased with modern HAIP, they remain potential concerns. The specific chemotherapeutic agents used may also influence the risk of hepatotoxicity. A comprehensive understanding of these potential complications, combined with thorough evaluation of individual patient factors and tumor characteristics, is crucial for optimizing patient selection with HAIP therapy. Despite these encouraging results, our study has notable limitations that warrant further discussion. As a single-center retrospective analysis spanning two sites, it is prone to selection bias and lacks generalizability, particularly given the absence of a control arm to directly compare HAIP + SCT against SCT alone. Progression-free survival assessment was not standardized, relying on physician records or imaging reports, which may introduce variability. Additionally, we did not distinguish between HAIP use as adjuvant therapy versus as treatment for unresectable disease, potentially conflating survival outcomes and obscuring conversion rates to resectability [ 20 , 33 ]. These emphasize the need for prospective, randomized controlled trials to definitively quantify HAIP’s incremental benefit over modern SCT. These trials, including the EA2222/PUMP trial, [ 26 , 34 ] will also refine patient selection criteria and assess HAIP’s role amidst evolving systemic therapy regimens. [ 2 , 35 ] Until then, our findings contribute real-world evidence supporting HAIP’s efficacy and safety, advocating for its consideration in multidisciplinary mCRC care while highlighting the necessity of robust, controlled studies to solidify its place in standard practice. In conclusion, this retrospective analysis indicates that HAIP combined with SCT offers a promising locoregional treatment approach for managing unresectable CRLM. By administering high doses of chemotherapy directly into hepatic circulation, HAIP therapy enhances tumor control compared to SCT alone, while minimizing systemic toxicity. Given that adequate liver function is crucial for patient tolerability and treatment success, careful assessment of these factors is essential prior to initiating HAIP therapy. This study bridges critical gaps by validating HAIP’s efficacy in pretreated populations, clarifying prognostic markers, and providing contemporary safety data. These insights refine patient selection criteria and support HAIP’s role in the evolving management of unresectable CRLM, particularly where systemic therapy has failed. Prospective trials are needed to confirm these findings, but this work lays a foundation for broader clinical adoption. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions : T.B. and N.V. contributed to the study conception, design, and methodology. They also provided supervision and resources for the project, with N.V. handling project administration. Investigation and data curation were performed by A.M. and M.S. M.S. conducted the formal data analysis and validation. For the manuscript's visuals, A.M. prepared Tables 1-4 and Supplemental Table 1, while M.S. prepared Figures 1-4. A.M. and M.S. wrote the original draft of the manuscript. All authors reviewed and edited the manuscript, with T.B. and N.V. providing critical revision for important intellectual content. All authors have read and approved the final manuscript. Data Availability: The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy regulations but are available from the corresponding author on reasonable request. Ethics Approval: This retrospective chart review study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the University of Texas Southwestern Medical Center. Consent to Participate: The Institutional Review Board of the University of Texas Southwestern Medical Center granted a waiver of informed consent for this study due to its retrospective nature. Consent to Publish: The Institutional Review Board of the University of Texas Southwestern Medical Center granted a waiver for consent to publish. References Siegel RL, Giaquinto AN, Jemal A, Cancer statistics. 2024. CA: A Cancer Journal for Clinicians . 2024;74(1):12–49. https://doi.org/10.3322/caac.21820 Patel RK, Rahman S, Schwantes IR, et al. Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations. Cell Mol Gastroenterol Hepatol. 2023;16(6):881–94. https://doi.org/10.1016/j.jcmgh.2023.08.012 . Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies. Br J Cancer. 2006;94(7):982–99. https://doi.org/10.1038/sj.bjc.6603033 . De Jong MC, Pulitano C, Ribero D, et al. Rates and Patterns of Recurrence Following Curative Intent Surgery for Colorectal Liver Metastasis. Ann Surg. 2009;250(3):440–8. https://doi.org/10.1097/sla.0b013e3181b4539b . Power DG, Healey-Bird BR, Kemeny NE. Regional Chemotherapy for Liver-Limited Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2008;7(4):247–59. https://doi.org/10.3816/ccc.2008.n.032 . Karanicolas PJ, Metrakos P, Chan K, et al. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol. 2013;21(1):129. https://doi.org/10.3747/co.21.1577 . Bolton JS, O'Connell MJ, Mahoney MR, et al. Hepatic Arterial Infusion and Systemic Chemotherapy After Multiple Metastasectomy in Patients With Colorectal Carcinoma Metastatic to the Liver: A North Central Cancer Treatment Group (NCCTG) Phase II Study, 92-46-52. Clin Colorectal Cancer. 2012;11(1):31–7. https://doi.org/10.1016/j.clcc.2011.03.029 . House MG, Kemeny NE, Gönen M, et al. Comparison of Adjuvant Systemic Chemotherapy With or Without Hepatic Arterial Infusional Chemotherapy After Hepatic Resection for Metastatic Colorectal Cancer. Ann Surg. 2011;254(6):851–6. https://doi.org/10.1097/sla.0b013e31822f4f88 . Kemeny MM, Adak S, Gray B, et al. Combined-Modality Treatment for Resectable Metastatic Colorectal Carcinoma to the Liver: Surgical Resection of Hepatic Metastases in Combination With Continuous Infusion of Chemotherapy—An Intergroup Study. J Clin Oncol. 2002;20(6):1499–505. https://doi.org/10.1200/jco.2002.20.6.1499 . Kemeny N, Huang Y, Cohen AM, et al. Hepatic Arterial Infusion of Chemotherapy after Resection of Hepatic Metastases from Colorectal Cancer. N Engl J Med. 1999;341(27):2039–48. https://doi.org/10.1056/nejm199912303412702 . Kemeny NE, Niedzwiecki D, Hollis DR, 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). J Clin Oncol. 2006;24(9):1395–403. https://doi.org/10.1200/jco.2005.03.8166 . Mocellin S, Pilati P, Lise M, Nitti D. Meta-Analysis of Hepatic Arterial Infusion for Unresectable Liver Metastases From Colorectal Cancer: The End of an Era? J Clin Oncol. 2007;25(35):5649–54. https://doi.org/10.1200/jco.2007.12.1764 . Niederhuber JE, Ensminger W, Gyves J, Thrall J, Walker S, Cozzi E. Regional chemotherapy of colorectal cancer metastatic to the liver. Cancer. 1984;53(6):1336–43. https://doi.org/10.1002/1097-0142(19840315)53:63.0.co;2-o . Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol. 1992;10(7):1112–8. https://doi.org/10.1200/jco.1992.10.7.1112 . Dhir M, Jones HL, Shuai Y, et al. Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case–Control Study. Ann Surg Oncol. 2017;24(1):150–8. https://doi.org/10.1245/s10434-016-5418-6 . Kemeny NE, Melendez FDH, Capanu M, et al. Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma. J Clin Oncol. 2009;27(21):3465–71. https://doi.org/10.1200/jco.2008.20.1301 . D'Angelica MI, Correa-Gallego C, Paty PB, et al. Phase II Trial of Hepatic Artery Infusional and Systemic Chemotherapy for Patients With Unresectable Hepatic Metastases From Colorectal Cancer. Ann Surg. 2015;261(2):353–60. https://doi.org/10.1097/sla.0000000000000614 . Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306–15. https://doi.org/10.1016/s1470-2045(15)00122-9 . Heinemann V, Von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75. https://doi.org/10.1016/s1470-2045(14)70330-4 . Verheij FS, Soares KC, Beets GL, et al. Timing of Primary Tumor Resection in Synchronous Metastatic Colon Cancer Patients Undergoing Hepatic Arterial Infusion Pump Placement. Ann Surg Oncol. 2022;29(3):2044–51. https://doi.org/10.1245/s10434-021-11029-3 . Abdel-Rahman O. Prognostic Value of Baseline ALBI Score Among Patients With Colorectal Liver Metastases: A Pooled Analysis of Two Randomized Trials. Article. Clin Colorectal Cancer. 2019;18(1):e61–8. https://doi.org/10.1016/j.clcc.2018.09.008 . Maleux G, Deroose C, Laenen A, et al. Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival. Acta Oncol. 2016;55(4):486–95. https://doi.org/10.3109/0284186x.2015.1101151 . Fiorentini G, Cantore M, Rossi S, et al. Hepatic arterial chemotherapy in combination with systemic chemotherapy compared with hepatic arterial chemotherapy alone for liver metastases from colorectal cancer: Results of a multi-centric randomized study. Article. Vivo. 2006;20(6 A):707–10. Kemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. Article. J Clin Oncol. 2005;23(22):4888–96. https://doi.org/10.1200/JCO.2005.07.100 . Ito K, Ito H, Kemeny NE, et al. Biliary sclerosis after hepatic arterial infusion pump chemotherapy for patients with colorectal cancer liver metastasis: Incidence, clinical features, and risk factors. Article. Ann Surg Oncol. 2012;19(5):1609–17. https://doi.org/10.1245/s10434-011-2102-8 . Group E-ACR, Randomized Phase A. III Study of Systemic Therapy With or Without Hepatic Arterial Infusion for Unresectable Colorectal Liver Metastases: The PUMP Trial. Updated November 5, 2024. Accessed July 2, 2025. https://www.clinicaltrials.gov/study/NCT05863195 László L, Kurilla A, Takács T, et al. Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology. Cells. 2021;10(3):667. https://doi.org/10.3390/cells10030667 . Steele CW, Whittle T, Smith JJ, Review. KRAS mutations are influential in driving hepatic metastases and predicting outcome in colorectal cancer. Chin Clin Oncol. 2019;8(5):53–53. https://doi.org/10.21037/cco.2019.08.16 . Boutin AT, Liao W-T, Wang M, et al. Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes Dev. 2017;31(4):370–82. https://doi.org/10.1101/gad.293449.116 . Golas MM, Gunawan B, Gutenberg A, et al. Cytogenetic signatures favoring metastatic organotropism in colorectal cancer. Nat Commun. 2025;16(1). https://doi.org/10.1038/s41467-025-58413-1 . Kemeny N, Daly J, Oderman P, et al. Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma. J Clin Oncol. 1984;2(6):595–600. https://doi.org/10.1200/jco.1984.2.6.595 . Italiano D. Hepatic Arterial Infusion Pump: Complications and Nursing Management Regarding Use in Patients With Colorectal Cancer. Clin J Oncol Nurs. 2018;22(3):340–6. https://doi.org/10.1188/18.cjon.340-346 . Pak LM, Kemeny NE, Capanu M, et al. Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential. J Surg Oncol. 2018;117(4):634–43. https://doi.org/10.1002/jso.24898 . Buisman FE, Homs MYV, Grünhagen DJ, 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. 2019;19(1). https://doi.org/10.1186/s12885-019-5515-6 . Zeineddine FA, Zeineddine MA, Yousef A, et al. Survival improvement for patients with metastatic colorectal cancer over twenty years. npj Precision Oncol. 2023;7(1). https://doi.org/10.1038/s41698-023-00353-4 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted Editorial decision: Revision requested 14 Oct, 2025 Reviews received at journal 13 Oct, 2025 Reviewers agreed at journal 17 Sep, 2025 Reviews received at journal 15 Sep, 2025 Reviewers agreed at journal 15 Sep, 2025 Reviews received at journal 10 Sep, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers invited by journal 12 Aug, 2025 Editor assigned by journal 10 Aug, 2025 Submission checks completed at journal 04 Aug, 2025 First submitted to journal 30 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7255848","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":502404958,"identity":"bc0fce08-a8fa-41a0-9edf-8d856baf0b7c","order_by":0,"name":"Allante Milsap","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Allante","middleName":"","lastName":"Milsap","suffix":""},{"id":502404959,"identity":"dc07dd80-9839-458c-9b98-f0cc275caf9d","order_by":1,"name":"Matthew Sawyer","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Sawyer","suffix":""},{"id":502404960,"identity":"d6668ae9-a177-47e6-91c1-782997805423","order_by":2,"name":"Syed Kazmi","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Syed","middleName":"","lastName":"Kazmi","suffix":""},{"id":502404961,"identity":"6d9fdc8f-991a-459d-bfc5-ccb612505a39","order_by":3,"name":"Radhika Kainthla","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Radhika","middleName":"","lastName":"Kainthla","suffix":""},{"id":502404962,"identity":"f64a9cce-a3c1-4f3d-b5bd-15ee40341607","order_by":4,"name":"Amy Jones","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Amy","middleName":"","lastName":"Jones","suffix":""},{"id":502404963,"identity":"0373c486-d77f-4374-869f-db92c3df18b0","order_by":5,"name":"Salwan Al Mutar","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Salwan","middleName":"Al","lastName":"Mutar","suffix":""},{"id":502404964,"identity":"4a966d75-f0ac-4829-882c-de8cd0c0af6c","order_by":6,"name":"Timothy Brown","email":"","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"","lastName":"Brown","suffix":""},{"id":502404965,"identity":"b0d46743-0385-40a0-8892-27235e4e46a3","order_by":7,"name":"Nilesh Verma","email":"data:image/png;base64,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","orcid":"","institution":"The University of Texas Southwestern Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Nilesh","middleName":"","lastName":"Verma","suffix":""}],"badges":[],"createdAt":"2025-07-30 19:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7255848/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7255848/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12029-026-01403-3","type":"published","date":"2026-01-21T15:58:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89564300,"identity":"7986056a-8019-415e-b8c9-4cff53709ef9","added_by":"auto","created_at":"2025-08-21 10:33:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17928,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Diagram of Patient Screening and Eligibility. Of 88 patients assessed for eligibility, 25 were excluded, resulting in 63 patients meeting criteria for study analysis\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7255848/v1/f5858e3e952c55b1ff17174b.png"},{"id":89564301,"identity":"394de546-f957-4c9a-a54c-9c175650df51","added_by":"auto","created_at":"2025-08-21 10:33:26","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34072,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival (OS) Following HAIP Placement. Kaplan-Meier analysis of OS for the study cohort (n=63), measured from the time of HAIP placement. Median OS was 38.0 months (95% CI 21.9–NR). The number of patients at risk is indicated at various time intervals below the curve\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7255848/v1/15e2e7ce97f676b3f4a8e832.jpeg"},{"id":89562446,"identity":"efcbe100-ee74-4236-a0db-dfbb1e826014","added_by":"auto","created_at":"2025-08-21 10:25:26","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":83032,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) Following HAIP Placement. Kaplan-Meier analysis of PFS for the study cohort (n=63), measured from the time of HAIP placement. Median PFS was 11.2 months (95% CI 7.1–16.1). The number of patients at risk is indicated at various time intervals below the curve\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7255848/v1/86a702143fc18058a3c5c769.jpeg"},{"id":101152067,"identity":"81b0ba97-611c-4a81-8d31-c1cef85584c9","added_by":"auto","created_at":"2026-01-26 16:09:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":846526,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7255848/v1/28d4ba57-5741-4f7a-b901-3114b241c34d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRetrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer (CRC) ranks as the third most diagnosed cancer in the United States, while standing as the second leading cause of cancer mortality.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Metastasis is detected in nearly a quarter of initial diagnoses of CRC, and ultimately develops in over half of patients overall [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Liver metastasis occurs in 70% of mCRC cases and is a primary driver of CRC-related mortality [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While surgical resection of colorectal liver metastasis (CRLM) is a potentially curative treatment option, only 10–20% of patients are eligible for this approach [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Of those who undergo resection of their CRLM, roughly half patients will develop recurrence within two years [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, it is imperative to explore alternative treatment strategies for CRLM.\u003c/p\u003e\u003cp\u003eHepatic arterial infusion (HAI) therapy is a vital locoregional treatment for patients with unresectable or recurrent CRLM. This approach leverages the liver's dual blood supply, where hepatic metastases are primarily perfused by the hepatic artery, while the normal liver parenchyma relies mostly on the portal vein. By delivering chemotherapy directly into the hepatic artery, HAI exploits the first-pass effect, where the liver extracts a high percentage of the drug before it reaches systemic circulation. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] This results in significantly higher drug concentrations at the tumor site while reducing systemic toxicity. Floxuridine (FUDR) is particularly effective for HAI due to its short half-life and ~ 95% hepatic extraction rate, achieving local drug concentrations 100- to 400-fold higher than those possible with standard intravenous administration.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Surgical implantation of a hepatic arterial infusion pump (HAIP) creates a safe and effective outpatient platform for continuous chemotherapy infusion over extended periods.\u003c/p\u003e\u003cp\u003eClinical evidence supports HAIP’s efficacy in improving outcomes for patients with CRLM, particularly in those with resected oligometastatic disease. Among these patients, the addition of HAIP-FUDR to SCT significantly enhances recurrence-free survival, liver recurrence-free survival, and overall survival (OS) compared SCT alone. [\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] A meta-analysis of ten randomized controlled trials further demonstrated a superior tumor response rate with HAIP (43% vs. 18%; relative risk: 2.26; p \u0026lt; 0.001). [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] In unresectable disease, HAIP’s efficacy is less established, though some studies report improved survival. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Despite these encouraging findings, HAIP therapy remains restricted to specialized centers due to the multidisciplinary expertise required for its safe and effective implementation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The broader adoption of HAIP is also hindered by persistent evidence gaps regarding optimal patient selection, outcomes in varied patient populations, and the lack of standardized treatment protocols.\u003c/p\u003e\u003cp\u003eTo address these challenges, this retrospective study evaluated the safety and efficacy of HAIP combined with SCT in patients with unresectable CRLM at an academic medical center and an affiliated safety-net hospital. The study assessed OS, progression-free survival (PFS), treatment-related complications, and potential prognostic factors in a diverse cohort, including recipients of both first-line and subsequent-line HAIP therapy. By examining real-world outcomes, this analysis aims to inform patient selection criteria, enhance the integration of HAIP into clinical practice, and underscore the need for prospective trials to establish standardized protocols for its use in unresectable CRLM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003ePatients\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCandidate patients were identified by querying pharmacy records to identify patients who had received hepatic arterial infusion chemotherapy from either Parkland Memorial Hospital or Clements University Hospital in Dallas, Texas from 2013 to 2023. Patients were eligible for inclusion if they had a diagnosis of colon or rectal cancer and received at least one cycle of HAI-FUDR. Patients who had progressed prior to chemotherapy administration or those who had alternative primary malignancies were not eligible for analysis.\u003c/p\u003e\u003cp\u003eBaseline covariates were collected from prior to HAI pump placement via chart review. These covariates include site of care (county hospital versus university hospital), demographics (age, gender, race, ethnicity), tumor characteristics (primary colon site, stage, \u003cem\u003eKRAS\u003c/em\u003e and \u003cem\u003eBRAF\u003c/em\u003e mutation status, mismatch repair status, size and number of liver metastases), baseline laboratory values (carcinoembryonic antigen, white blood cell count, hemoglobin, platelet count, total bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) and treatment data (types and number of chemotherapy lines received prior to HAI placement). Baseline covariates were extracted by the authors (M.S. and A.M.).\u003c/p\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome of interest was overall survival from date of pump placement. Secondary outcomes of interest included PFS, a composite of progression or death, as assessed by records from the treating physician or from imaging reports confirming progression.\u003c/p\u003e\u003cp\u003eTime-to-event outcomes were analyzed using the Kaplan Meier method with an index date of hepatic arterial infusion pump placement until date of outcome of interest. Patients who had not met the outcome of interest were censored at the date of last clinical contact where vital status could be ascertained.\u003c/p\u003e\u003cp\u003eTo identify covariates associated with outcomes, multivariate Cox regression models were constructed following Collett’s four-step hybrid approach to model building. Briefly, all baseline covariates were analyzed in a univariate model. Those with a significance level of p ≤ 0.1 were analyzed in a multivariate model. Covariates were individually eliminated until a final model was reached in which all covariates met a significance of p ≤ 0.05. Eliminated models were then tested one-by-one and were retained if p ≤ 0.05. The final model was evaluated for goodness of fit using Cox Snell residuals, Akaike information criterion (AIC), and Bayesian information criterion (BIC).\u003c/p\u003e\u003cp\u003eAll statistical analyses were performed using Stata v18.0 (College Station, TX).\u003c/p\u003e\u003cp\u003e\u003cb\u003eOversight\u003c/b\u003e\u003c/p\u003e\u003cp\u003e This study was reviewed by the Institutional Review Board of the University of Texas Southwestern Medical Center and granted a waiver of consent.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003ePatient Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFrom 88 patients evaluated, 63 met inclusion criteria for this analysis, with the majority (n\u0026thinsp;=\u0026thinsp;47, 75%) treated at the University site (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age at inclusion was 46 years (Interquartile Range [IQR] 41\u0026ndash;57), and just over half of the patients were male (n\u0026thinsp;=\u0026thinsp;34, 54%).\u003c/p\u003e\u003cp\u003eOf the patients included, 48 (76%) had greater than 11 hepatic metastases. Primary tumors were predominantly left-sided, originating in the descending/sigmoid colon or rectum (n\u0026thinsp;=\u0026thinsp;43, 68%). The median size of the largest lesion was 3.0 cm (IQR 2.1-6.0). Tumor stage T3 (n\u0026thinsp;=\u0026thinsp;34, 54%) and nodal stage N2 (n\u0026thinsp;=\u0026thinsp;26, 41%) were frequently observed. Prior to HAIP placement, 29 (44%) patients had received resection of their primary CRC, while 35 (56%) patients had their CRC resected concurrently with HAIP placement. Most patients had received prior systemic therapy, commonly one (n\u0026thinsp;=\u0026thinsp;38, 60%) or two (n\u0026thinsp;=\u0026thinsp;18, 29%) lines before HAIP initiation. Further baseline characteristics are detailed in Table\u0026nbsp;1 and Supplemental Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eTotal, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eSites, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eUT Southwestern Medical Center\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e47 (75%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eParkland Memorial Hospital\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAge, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e46 (41\u0026ndash;57)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eGender, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34 (54%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eRace, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eWhite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e50 (79%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eBlack\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eAsian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 ( 5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 ( 6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eEthnicity, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eHispanic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eNon-Hispanic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e41 (65%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eDecline/Unknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003ePrimary Tumor Site, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eAscending Colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (21%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eTransverse Colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (11%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eDescending Colon or Sigmoid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32 (51%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eRectum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003ePrimary tumor stage, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"6\" nameend=\"c2\" namest=\"c1\" rowspan=\"7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 ( 2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 ( 8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34 (54%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT4a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (13%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eT4b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 ( 5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"8\" nameend=\"c2\" namest=\"c1\" rowspan=\"9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10 (16%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 ( 6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 ( 8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN1b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN1c\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 ( 5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10 (16%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN2a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (21%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eN2b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 ( 5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 ( 6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eKRAS Mutation, (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e31 (49%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e31 (49%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 ( 2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eBRAF Mutation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e60 (95%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 ( 3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 ( 2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eMismatch Repair Deficient, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 ( 0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eLargest Liver Metastasis, median (I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 cm (2.1-6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eNumber of Liver Metastases, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 ( 2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003e1\u0026ndash;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (11%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003e5\u0026ndash;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 ( 8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003e\u0026ge;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e48 (76%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 ( 3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003ePrimary CRC resection, n (%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eDuring HAIP placement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35, (56%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003ePrior to HAIP placement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29, (44%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eNumber of Chemocycles Prior to HAIP, median\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eDays to Initiation of HAIP chemotherapy, median\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eHAIP Chemotherapy provided, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eFUDR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e63 (100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eSystemic therapy during HAIP treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eFOLFOX-based\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30 (48%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eFOLFIRI-based\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (19%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eFOLFOXIRI-based\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9 (14.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e*missing n\u0026thinsp;=\u0026thinsp;3\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eTable\u0026nbsp;1.\u003c/b\u003e Baseline Patient and Tumor Characteristics. Summary of demographic, clinical, molecular, metastatic disease, and treatment characteristics for the study cohort (n\u0026thinsp;=\u0026thinsp;63) at baseline. IQR, interquartile range; n, number\u003c/p\u003e\u003cp\u003e\u003cb\u003eSurvival\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe median overall survival from the time of HAIP placement was 38.0 months (95% CI 21.9-NR) and median PFS was 11.2 months (95% CI 7.1\u0026ndash;16.1) (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and 3). Kaplan-Meier overall survival is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Baseline bilirubin, KRAS mutant status, and CEA were associated with OS in the univariate Cox model (Fig.\u0026nbsp;4, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, the attempt to build a multivariate model was unsuccessful as the only significant covariate was baseline bilirubin (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). KRAS mutation was retained in the multivariate model due to significant \u003cem\u003ea priori\u003c/em\u003e belief on impact on outcomes.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate Predictors of Overall Survival (OS). Results from univariate Cox proportional hazards regression analysis. Baseline total bilirubin (HR 6.86, 95% CI 1.42\u0026ndash;33.13, p\u0026thinsp;=\u0026thinsp;0.02), KRAS mutant status (ref\u0026thinsp;=\u0026thinsp;no; HR 3.7, 95% CI 1.09\u0026ndash;12.53, p\u0026thinsp;=\u0026thinsp;0.035), and baseline CEA (HR 0.94, 95% CI 0.90-1.00, p\u0026thinsp;=\u0026thinsp;0.037) were identified as significant predictors of OS\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnivariate Cox OS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline Total Bilirubin ( per mg/dL)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.42\u0026ndash;33.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKRAS Mutant (ref\u0026thinsp;=\u0026thinsp;no)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.09\u0026ndash;12.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline CEA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.90-1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate Predictors of Overall Survival (OS). Results from multivariate Cox proportional hazards regression analysis. After adjusting for covariates, baseline total bilirubin remained an independent predictor of overall survival (HR 3.87, 95% CI 1.20-12.44, p\u0026thinsp;=\u0026thinsp;0.02), whereas KRAS mutant status (ref\u0026thinsp;=\u0026thinsp;no) was no longer statistically significant (HR 1.47, 95% CI 0.76\u0026ndash;2.86, p\u0026thinsp;=\u0026thinsp;0.25)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultivariate Cox OS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline Total Bilirubin ( per mg/dL)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.20-12.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKRAS Mutant (ref\u0026thinsp;=\u0026thinsp;no)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.76\u0026ndash;2.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eToxicity\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAcute complications specifically related to the HAIP pump placement occurred in 11 patients (17.5%). The most common of these acute events were pump-site hematoma, observed in 4 patients (6.4%), and pump infection, occurring in 2 patients (3.2%). Several less frequent complications were noted, each occurring in a single patient (1.6% each): ventral hernia, post-operative abdominal pain requiring assessment, pump tip migration, evidence of extrahepatic perfusion, and the need for pump replacement (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Grade 3 toxicities from FUDR infusion were infrequent, involving alkaline phosphatase (n\u0026thinsp;=\u0026thinsp;6), AST or ALT elevation (n\u0026thinsp;=\u0026thinsp;3), bilirubin increase (n\u0026thinsp;=\u0026thinsp;2), and platelet count decrease (n\u0026thinsp;=\u0026thinsp;1) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHAIP-Related Complications and Toxicities. Acute complications from HAIP pump placement occurred in 17.46% of patients (n\u0026thinsp;=\u0026thinsp;11), most commonly hematoma (6.35%) and pump site infection (3.17%). Chemotherapy-related laboratory toxicities are stratified by the highest severity grade, with liver function test elevations (Alk Phos, AST, ALT) being the most frequent abnormalities observed. Grade 3 bilirubin elevation occurred in two patients and Grade 3 decrease in platelets occurred in one patient\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAcute pump related complications, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e11 (17.46%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eHematoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e4\u0026nbsp;(6.35%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003ePump Infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e2\u0026nbsp;(3.17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eVentral Hernia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u0026nbsp;(1.59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eAbdominal Pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u0026nbsp;(1.59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003ePump Tip Migration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u0026nbsp;(1.59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eExtrahepatic Perfusion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u0026nbsp;(1.59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003ePump Replacement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u0026nbsp;(1.59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHAIP Laboratory Toxicities, by Grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 1, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eGrade 2, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 3, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTotal, n\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlk Phos Elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAST Elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eALT Elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIncrease in Bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDecrease in Platelet\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective analysis evaluated the efficacy and safety of HAIP chemotherapy combined with SCT in 63 patients with unresectable CRLM. The primary efficacy end points were a median OS of 38.0 months (95% CI 21.9\u0026ndash;NR) and a median PFS of 11.2 months (95% CI 7.1\u0026ndash;16.1). Notably, these survival outcomes were achieved in a heavily pre-treated population with a high disease burden, in which 76% of patients presented with 11 or more liver metastases and 40% had received prior SCT. Our analysis also identified baseline total bilirubin as the sole independent predictor of OS (HR 3.87; 95% CI 1.20\u0026ndash;12.44; p\u0026thinsp;=\u0026thinsp;0.02). HAIP treatment was associated with a manageable safety profile; acute pump-related complications occurred in 17.5% of patients, with a modest incidence of Grade 3 toxicities related to FUDR infusion. The results of this analysis suggest that HAIP with SCT is a safe and effective locoregional approach for this patient population.\u003c/p\u003e\u003cp\u003eThe median OS of 38.0 months achieved in our cohort falls within the upper range of 33\u0026ndash;38 months reported in similar investigations among cohorts treated with HAIP and SCT [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This result is particularly significant when contrasted with outcomes from modern SCT alone. For instance, the TRIBE trial reported a median OS of 29.8 months with first-line FOLFOXIRI plus bevacizumab regimen, and a median OS of 25.8 months in the FOLFIRI plus bevacizumab group [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Similarly, the FIRE-3 trial, which compared first-line FOLFIRI plus either cetuximab or bevacizumab, demonstrated a median OS of 28.7 months in the cetuximab group and 25.0 months in the bevacizumab group.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Notably, our 38.0-month survival surpassed these benchmarks even though 40% of our patients had prior exposure to SCT, which contrasts sharply with the exclusively chemotherapy-na\u0026iuml;ve populations enrolled in TRIBE and FIRE-3. The true magnitude of this survival advantage is best illustrated in a direct comparison of chemotherapy-na\u0026iuml;ve patients, where adding HAIP to SCT has been shown to elevate the median OS to 53 months. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eA key finding from this analysis was that baseline total bilirubin emerged as the sole statistically significant, independent predictor of overall survival, conferring a nearly four-fold increase in the risk of death (HR 3.87). Our observation aligns with other investigations that have established elevated bilirubin as a negative prognostic indicator for survival in CRLM.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Baseline bilirubin serves as a direct surrogate for hepatic reserve; higher levels indicate a compromised liver less able to tolerate the well-documented biliary toxicity of HAIP chemotherapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This treatment-related toxicity can manifest as further bilirubin elevation and, in severe cases, biliary sclerosis [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Consequently, patients with higher baseline bilirubin face increased risks of dose-limiting toxicities and treatment interruptions, adversely impacting survival. The clinical relevance of this principle is now validated by the eligibility criteria of major clinical trials, such as the active phase III EA2222/PUMP study, which mandates a strict baseline total bilirubin cutoff of \u0026le;\u0026thinsp;1.5 mg/dL.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Our data support using baseline bilirubin for risk stratification and suggest that HAIP therapy may be most beneficial when initiated earlier in the disease course, before the onset of significant liver dysfunction or extensive biliary involvement.\u003c/p\u003e\u003cp\u003eIn our cohort, KRAS mutations were associated with worse OS in univariate analysis (HR 3.7, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035), though this did not retain statistical significance after adjusting for bilirubin (HR 1.47, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25). This trend aligns with established KRAS-driven tumor biology: activating mutations in KRAS\u0026mdash;present in 40\u0026ndash;50% of colorectal cancers (CRCs)\u0026mdash;constitutively activate MAPK signaling through impaired GTP hydrolysis and sustained GTP-bound states, promoting aggressive phenotypes including enhanced metastatic potential and metabolic reprogramming such as the Warburg effect.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] KRAS-mutant tumors exhibit intrinsic chemoresistance through multiple mechanisms: (1) upregulation of drug efflux pumps (e.g., ABCB1/MDR1), (2) anti-apoptotic BCL-2 overexpression, and (3) creation of an immunosuppressive tumor microenvironment via PD-L1 induction and T-cell exclusion.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] These properties may compromise HAIP efficacy, as the cytotoxic agent floxuridine (FUDR) relies on cellular uptake and apoptosis induction. Clinically, KRAS mutations correlate with reduced OS after liver metastasis resection and increased extrahepatic recurrence.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] Notably, while KRAS mutations impair response to anti-EGFR agents, the HAIP/SCT regimen did not include EGFR inhibitors. The attenuated hazard ratio (HR) for KRAS-mutant tumors in multivariate analysis suggests bilirubin\u0026mdash;a marker of hepatic dysfunction\u0026mdash;may be a stronger pharmacokinetic determinant than KRAS status. However, the persistent directional trend toward worse outcomes in KRAS-mutant subgroups warrants further study, especially given KRAS's role in liver and lung metastasis tropism via mechanisms like TGF-β pathway activation [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and chromosomal imbalances (e.g., KRAS amplification in brain metastases).[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eEvaluation of patient candidacy for HAIP therapy warrants careful consideration of its potential benefits against its risks. Early methods of chemotherapy administration via hepatic arterial infusion (HAI) were associated with significant adverse events, such as severe gastrointestinal toxicity (46%) and hepatic enzyme abnormalities (71%).[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Contemporary HAIP, however, demonstrates a substantially improved safety profile given advances in pump devices, surgical techniques, and chemotherapy regimens [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Our data supports this improvement, showing an overall grade 3 toxicity rate of 9.52% (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In our cohort, procedure-related complications included hematoma (6.35%) and pump-site infection (3.17%). Pump-related issues, such as seroma formation, and catheter-related complications like malposition and extravasation also occurred, highlighting the need for meticulous surgical technique and careful post-procedural monitoring. While the incidence of hepatic toxicities, such as chemical hepatitis and biliary sclerosis, has decreased with modern HAIP, they remain potential concerns. The specific chemotherapeutic agents used may also influence the risk of hepatotoxicity. A comprehensive understanding of these potential complications, combined with thorough evaluation of individual patient factors and tumor characteristics, is crucial for optimizing patient selection with HAIP therapy.\u003c/p\u003e\u003cp\u003eDespite these encouraging results, our study has notable limitations that warrant further discussion. As a single-center retrospective analysis spanning two sites, it is prone to selection bias and lacks generalizability, particularly given the absence of a control arm to directly compare HAIP\u0026thinsp;+\u0026thinsp;SCT against SCT alone. Progression-free survival assessment was not standardized, relying on physician records or imaging reports, which may introduce variability. Additionally, we did not distinguish between HAIP use as adjuvant therapy versus as treatment for unresectable disease, potentially conflating survival outcomes and obscuring conversion rates to resectability [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. These emphasize the need for prospective, randomized controlled trials to definitively quantify HAIP\u0026rsquo;s incremental benefit over modern SCT. These trials, including the EA2222/PUMP trial, [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] will also refine patient selection criteria and assess HAIP\u0026rsquo;s role amidst evolving systemic therapy regimens. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] Until then, our findings contribute real-world evidence supporting HAIP\u0026rsquo;s efficacy and safety, advocating for its consideration in multidisciplinary mCRC care while highlighting the necessity of robust, controlled studies to solidify its place in standard practice.\u003c/p\u003e\u003cp\u003eIn conclusion, this retrospective analysis indicates that HAIP combined with SCT offers a promising locoregional treatment approach for managing unresectable CRLM. By administering high doses of chemotherapy directly into hepatic circulation, HAIP therapy enhances tumor control compared to SCT alone, while minimizing systemic toxicity. Given that adequate liver function is crucial for patient tolerability and treatment success, careful assessment of these factors is essential prior to initiating HAIP therapy. This study bridges critical gaps by validating HAIP\u0026rsquo;s efficacy in pretreated populations, clarifying prognostic markers, and providing contemporary safety data. These insights refine patient selection criteria and support HAIP\u0026rsquo;s role in the evolving management of unresectable CRLM, particularly where systemic therapy has failed. Prospective trials are needed to confirm these findings, but this work lays a foundation for broader clinical adoption.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e: T.B. and N.V. contributed to the study conception, design, and methodology. They also provided supervision and resources for the project, with N.V. handling project administration. Investigation and data curation were performed by A.M. and M.S. M.S. conducted the formal data analysis and validation. For the manuscript\u0026apos;s visuals, A.M. prepared Tables 1-4 and Supplemental Table 1, while M.S. prepared Figures 1-4. A.M. and M.S. wrote the original draft of the manuscript. All authors reviewed and edited the manuscript, with T.B. and N.V. providing critical revision for important intellectual content. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy regulations but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e This retrospective chart review study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the University of Texas Southwestern Medical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u003c/strong\u003e The Institutional Review Board of the University of Texas Southwestern Medical Center granted a waiver of informed consent for this study due to its retrospective nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish:\u003c/strong\u003e The Institutional Review Board of the University of Texas Southwestern Medical Center granted a waiver for consent to publish.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Giaquinto AN, Jemal A, Cancer statistics. 2024. \u003cem\u003eCA: A Cancer Journal for Clinicians\u003c/em\u003e. 2024;74(1):12\u0026ndash;49. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3322/caac.21820\u003c/span\u003e\u003cspan address=\"10.3322/caac.21820\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatel RK, Rahman S, Schwantes IR, et al. Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations. Cell Mol Gastroenterol Hepatol. 2023;16(6):881\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jcmgh.2023.08.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jcmgh.2023.08.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSimmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies. Br J Cancer. 2006;94(7):982\u0026ndash;99. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/sj.bjc.6603033\u003c/span\u003e\u003cspan address=\"10.1038/sj.bjc.6603033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Jong MC, Pulitano C, Ribero D, et al. Rates and Patterns of Recurrence Following Curative Intent Surgery for Colorectal Liver Metastasis. Ann Surg. 2009;250(3):440\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/sla.0b013e3181b4539b\u003c/span\u003e\u003cspan address=\"10.1097/sla.0b013e3181b4539b\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePower DG, Healey-Bird BR, Kemeny NE. Regional Chemotherapy for Liver-Limited Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2008;7(4):247\u0026ndash;59. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3816/ccc.2008.n.032\u003c/span\u003e\u003cspan address=\"10.3816/ccc.2008.n.032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaranicolas PJ, Metrakos P, Chan K, et al. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol. 2013;21(1):129. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3747/co.21.1577\u003c/span\u003e\u003cspan address=\"10.3747/co.21.1577\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBolton JS, O'Connell MJ, Mahoney MR, et al. Hepatic Arterial Infusion and Systemic Chemotherapy After Multiple Metastasectomy in Patients With Colorectal Carcinoma Metastatic to the Liver: A North Central Cancer Treatment Group (NCCTG) Phase II Study, 92-46-52. Clin Colorectal Cancer. 2012;11(1):31\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clcc.2011.03.029\u003c/span\u003e\u003cspan address=\"10.1016/j.clcc.2011.03.029\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHouse MG, Kemeny NE, G\u0026ouml;nen M, et al. Comparison of Adjuvant Systemic Chemotherapy With or Without Hepatic Arterial Infusional Chemotherapy After Hepatic Resection for Metastatic Colorectal Cancer. Ann Surg. 2011;254(6):851\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/sla.0b013e31822f4f88\u003c/span\u003e\u003cspan address=\"10.1097/sla.0b013e31822f4f88\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny MM, Adak S, Gray B, et al. Combined-Modality Treatment for Resectable Metastatic Colorectal Carcinoma to the Liver: Surgical Resection of Hepatic Metastases in Combination With Continuous Infusion of Chemotherapy\u0026mdash;An Intergroup Study. J Clin Oncol. 2002;20(6):1499\u0026ndash;505. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.2002.20.6.1499\u003c/span\u003e\u003cspan address=\"10.1200/jco.2002.20.6.1499\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny N, Huang Y, Cohen AM, et al. Hepatic Arterial Infusion of Chemotherapy after Resection of Hepatic Metastases from Colorectal Cancer. N Engl J Med. 1999;341(27):2039\u0026ndash;48. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/nejm199912303412702\u003c/span\u003e\u003cspan address=\"10.1056/nejm199912303412702\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny NE, Niedzwiecki D, Hollis DR, 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). J Clin Oncol. 2006;24(9):1395\u0026ndash;403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.2005.03.8166\u003c/span\u003e\u003cspan address=\"10.1200/jco.2005.03.8166\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMocellin S, Pilati P, Lise M, Nitti D. Meta-Analysis of Hepatic Arterial Infusion for Unresectable Liver Metastases From Colorectal Cancer: The End of an Era? J Clin Oncol. 2007;25(35):5649\u0026ndash;54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.2007.12.1764\u003c/span\u003e\u003cspan address=\"10.1200/jco.2007.12.1764\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNiederhuber JE, Ensminger W, Gyves J, Thrall J, Walker S, Cozzi E. Regional chemotherapy of colorectal cancer metastatic to the liver. Cancer. 1984;53(6):1336\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/1097-0142(19840315)53:6\u0026lt;1336::aid-cncr2820530620\u0026gt;3.0.co;2-o\u003c/span\u003e\u003cspan address=\"10.1002/1097-0142(19840315)53:6%3C1336::aid-cncr2820530620%3E3.0.co;2-o\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol. 1992;10(7):1112\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.1992.10.7.1112\u003c/span\u003e\u003cspan address=\"10.1200/jco.1992.10.7.1112\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDhir M, Jones HL, Shuai Y, et al. Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case\u0026ndash;Control Study. Ann Surg Oncol. 2017;24(1):150\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1245/s10434-016-5418-6\u003c/span\u003e\u003cspan address=\"10.1245/s10434-016-5418-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny NE, Melendez FDH, Capanu M, et al. Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma. J Clin Oncol. 2009;27(21):3465\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.2008.20.1301\u003c/span\u003e\u003cspan address=\"10.1200/jco.2008.20.1301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eD'Angelica MI, Correa-Gallego C, Paty PB, et al. Phase II Trial of Hepatic Artery Infusional and Systemic Chemotherapy for Patients With Unresectable Hepatic Metastases From Colorectal Cancer. Ann Surg. 2015;261(2):353\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/sla.0000000000000614\u003c/span\u003e\u003cspan address=\"10.1097/sla.0000000000000614\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s1470-2045(15)00122-9\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(15)00122-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeinemann V, Von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s1470-2045(14)70330-4\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(14)70330-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVerheij FS, Soares KC, Beets GL, et al. Timing of Primary Tumor Resection in Synchronous Metastatic Colon Cancer Patients Undergoing Hepatic Arterial Infusion Pump Placement. Ann Surg Oncol. 2022;29(3):2044\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1245/s10434-021-11029-3\u003c/span\u003e\u003cspan address=\"10.1245/s10434-021-11029-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdel-Rahman O. Prognostic Value of Baseline ALBI Score Among Patients With Colorectal Liver Metastases: A Pooled Analysis of Two Randomized Trials. Article. Clin Colorectal Cancer. 2019;18(1):e61\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clcc.2018.09.008\u003c/span\u003e\u003cspan address=\"10.1016/j.clcc.2018.09.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaleux G, Deroose C, Laenen A, et al. Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival. Acta Oncol. 2016;55(4):486\u0026ndash;95. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3109/0284186x.2015.1101151\u003c/span\u003e\u003cspan address=\"10.3109/0284186x.2015.1101151\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFiorentini G, Cantore M, Rossi S, et al. Hepatic arterial chemotherapy in combination with systemic chemotherapy compared with hepatic arterial chemotherapy alone for liver metastases from colorectal cancer: Results of a multi-centric randomized study. Article. Vivo. 2006;20(6 A):707\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. Article. J Clin Oncol. 2005;23(22):4888\u0026ndash;96. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/JCO.2005.07.100\u003c/span\u003e\u003cspan address=\"10.1200/JCO.2005.07.100\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIto K, Ito H, Kemeny NE, et al. Biliary sclerosis after hepatic arterial infusion pump chemotherapy for patients with colorectal cancer liver metastasis: Incidence, clinical features, and risk factors. Article. Ann Surg Oncol. 2012;19(5):1609\u0026ndash;17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1245/s10434-011-2102-8\u003c/span\u003e\u003cspan address=\"10.1245/s10434-011-2102-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGroup E-ACR, Randomized Phase A. III Study of Systemic Therapy With or Without Hepatic Arterial Infusion for Unresectable Colorectal Liver Metastases: The PUMP Trial. Updated November 5, 2024. Accessed July 2, 2025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.clinicaltrials.gov/study/NCT05863195\u003c/span\u003e\u003cspan address=\"https://www.clinicaltrials.gov/study/NCT05863195\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eL\u0026aacute;szl\u0026oacute; L, Kurilla A, Tak\u0026aacute;cs T, et al. Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology. Cells. 2021;10(3):667. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cells10030667\u003c/span\u003e\u003cspan address=\"10.3390/cells10030667\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSteele CW, Whittle T, Smith JJ, Review. KRAS mutations are influential in driving hepatic metastases and predicting outcome in colorectal cancer. Chin Clin Oncol. 2019;8(5):53\u0026ndash;53. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21037/cco.2019.08.16\u003c/span\u003e\u003cspan address=\"10.21037/cco.2019.08.16\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoutin AT, Liao W-T, Wang M, et al. Oncogenic\u0026thinsp;\u0026lt;\u0026thinsp;i\u0026thinsp;\u0026gt;\u0026thinsp;Kras\u0026thinsp;drives invasion and maintains metastases in colorectal cancer. Genes Dev. 2017;31(4):370\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/gad.293449.116\u003c/span\u003e\u003cspan address=\"10.1101/gad.293449.116\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGolas MM, Gunawan B, Gutenberg A, et al. Cytogenetic signatures favoring metastatic organotropism in colorectal cancer. Nat Commun. 2025;16(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41467-025-58413-1\u003c/span\u003e\u003cspan address=\"10.1038/s41467-025-58413-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemeny N, Daly J, Oderman P, et al. Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma. J Clin Oncol. 1984;2(6):595\u0026ndash;600. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/jco.1984.2.6.595\u003c/span\u003e\u003cspan address=\"10.1200/jco.1984.2.6.595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eItaliano D. Hepatic Arterial Infusion Pump: Complications and Nursing Management Regarding Use in Patients With Colorectal Cancer. Clin J Oncol Nurs. 2018;22(3):340\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1188/18.cjon.340-346\u003c/span\u003e\u003cspan address=\"10.1188/18.cjon.340-346\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePak LM, Kemeny NE, Capanu M, et al. Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential. J Surg Oncol. 2018;117(4):634\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jso.24898\u003c/span\u003e\u003cspan address=\"10.1002/jso.24898\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBuisman FE, Homs MYV, Gr\u0026uuml;nhagen DJ, et al. Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases \u0026ndash; the multicenter randomized controlled PUMP trial. BMC Cancer. 2019;19(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12885-019-5515-6\u003c/span\u003e\u003cspan address=\"10.1186/s12885-019-5515-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZeineddine FA, Zeineddine MA, Yousef A, et al. Survival improvement for patients with metastatic colorectal cancer over twenty years. npj Precision Oncol. 2023;7(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41698-023-00353-4\u003c/span\u003e\u003cspan address=\"10.1038/s41698-023-00353-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Hepatic Arterial Infusion Pump (HAIP), Colorectal Liver Metastasis, Floxuridine, Overall Survival, Prognostic Factors, Locoregional Therapy","lastPublishedDoi":"10.21203/rs.3.rs-7255848/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7255848/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eHepatic arterial infusion pump (HAIP) therapy is a promising treatment for metastatic colorectal cancer (mCRC) with liver metastases, delivering targeted therapy to improve efficacy and reduce systemic toxicity. This retrospective study evaluates HAIP outcomes at an academic center and safety net hospital.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients with mCRC and liver metastases receiving at least one HAIP floxuridine (FUDR) cycle from 2013 to 2023 were included. Baseline data on demographics, tumor characteristics, and prior treatments were collected. The primary outcome was overall survival (OS) post-pump placement, with secondary outcomes of real-world progression-free survival (rwPFS) and HAIP-related complications.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf 88 patients assessed, 63 met inclusion criteria. Median age was 46 years (IQR 41\u0026ndash;57); 54% were male. Prior to HAIP, 60% (n\u0026thinsp;=\u0026thinsp;38) received one line of systemic therapy, and 29% (n\u0026thinsp;=\u0026thinsp;18) received two. Median OS was 38.0 months (95% CI 21.9\u0026ndash;not reached), and median rwPFS was 11.2 months (95% CI 7.1\u0026ndash;16.1). Univariate analysis linked baseline bilirubin, KRAS mutation, and CEA levels to OS. However, only elevated baseline bilirubin remained an independent predictor of worse survival in the final multivariate model. Common complications were hematoma (6.4%, n\u0026thinsp;=\u0026thinsp;4) and pump infection (3.2%, n\u0026thinsp;=\u0026thinsp;2). Grade 3 FUDR toxicities were rare: elevated alkaline phosphatase (n\u0026thinsp;=\u0026thinsp;6), AST/ALT (n\u0026thinsp;=\u0026thinsp;3), bilirubin (n\u0026thinsp;=\u0026thinsp;2), and thrombocytopenia (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eHAIP treatment with FUDR is an effective treatment option for patients with mCRC and hepatic metastasis. HAIP treatment is associated with enhanced survival outcomes and limited rates of complications. Prospective, randomized studies are needed to confirm HAIP's role in mCRC management.\u003c/p\u003e","manuscriptTitle":"Retrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 10:25:21","doi":"10.21203/rs.3.rs-7255848/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-15T01:45:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-13T10:40:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"223679695947242798648162496004274475201","date":"2025-09-17T18:36:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-15T21:36:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162871016385641924786457415008882695050","date":"2025-09-15T15:24:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-10T20:06:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62090286095984562414895663379682414328","date":"2025-08-18T06:05:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-13T01:53:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-10T10:40:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-04T04:06:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Gastrointestinal Cancer","date":"2025-07-30T19:06:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5442fdca-9626-48fa-ac2f-c098c546b62d","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:06:33+00:00","versionOfRecord":{"articleIdentity":"rs-7255848","link":"https://doi.org/10.1007/s12029-026-01403-3","journal":{"identity":"journal-of-gastrointestinal-cancer","isVorOnly":false,"title":"Journal of Gastrointestinal Cancer"},"publishedOn":"2026-01-21 15:58:11","publishedOnDateReadable":"January 21st, 2026"},"versionCreatedAt":"2025-08-21 10:25:21","video":"","vorDoi":"10.1007/s12029-026-01403-3","vorDoiUrl":"https://doi.org/10.1007/s12029-026-01403-3","workflowStages":[]},"version":"v1","identity":"rs-7255848","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7255848","identity":"rs-7255848","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}