Safety and Efficacy of trans-arterial Infusion Chemotherapy Combined with Lipiodol Chemoembolization for Advanced Colorectal Cancer: A Prospective Single-Center Clinical Study of 239 Patients in China

Safety and Efficacy of trans-arterial Infusion Chemotherapy Combined with Lipiodol Chemoembolization for Advanced Colorectal Cancer: A Prospective Single-Center Clinical Study of 239 Patients in China | 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 Safety and Efficacy of trans-arterial Infusion Chemotherapy Combined with Lipiodol Chemoembolization for Advanced Colorectal Cancer: A Prospective Single-Center Clinical Study of 239 Patients in China Jiajia Zhang, Xieyi Guo, Yishu Ma, Meipan Yin, Gang Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7035014/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Advanced colorectal cancer (CRC) patients who are ineligible for surgery or have failed standard treatments face limited therapeutic options. Trans-arterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization may offer a targeted, effective intervention to improve outcomes in this population. Methods: In this prospective single-center study, 239 patients with advanced CRC received one to three sessions of intra-arterial infusion of oxaliplatin and raltitrexed, followed by embolization using a lipiodol-doxorubicin emulsion targeting tumor-feeding arteries. Treatment response was assessed using RECIST criteria. Safety, survival outcomes, and symptom relief were evaluated during follow-up. Descriptive and survival statistics were calculated using standard methods. Results: The disease control rate was 94.6%, with an objective response rate of 59.4%. Median overall survival was 21.7 months, and the mean follow-up duration was 20.1 months. Common adverse events included nausea (65.1%), abdominal discomfort (38.2%), tenesmus (39.8%), and myelosuppression (46.8%). All side effects were manageable with supportive care, and no serious perioperative complications such as intestinal necrosis or perforation occurred. Symptomatic relief was particularly notable in patients with tumor-related bleeding or obstruction. Most patients maintained a good performance status (ECOG 0–1) throughout follow-up. Conclusions: Super selective TAI combined with lipiodol chemoembolization appears to be a safe and effective locoregional treatment strategy for patients with advanced CRC. It offers promising disease control, symptomatic relief, and survival benefit, with tolerable toxicity. These findings support further prospective, multicenter randomized trials to validate clinical utility and refine patient selection criteria. Colorectal cancer Trans-arterial infusion chemotherapy Lipiodol chemoembolization Interventional oncology Advanced-stage cancer treatment Figures Figure 1 Figure 2 Figure 3 1. Background Colorectal cancer (CRC) remains a significant global health burden, ranking third in incidence and second in mortality among all cancers worldwide [ 1 ]. Surgical resection is the cornerstone of curative treatment for localized CRC [ 2 , 3 ]. However, 40–50% of patients present with advanced disease and distant metastases, rendering them ineligible for surgery. Additionally, a considerable number experience recurrence after radical resection, have contraindications to surgery, or decline surgical options, leading to poor prognoses with a 5-year overall survival rate below 10% [ 4 , 5 ]. For patients unsuitable for surgery, systemic chemotherapy, typically fluoropyrimidine-based regimens such as FOLFOX or CAPEOX, is the standard first-line treatment. In selected cases, neoadjuvant chemotherapy enables tumor downstaging, allowing subsequent resection and improved survival outcomes [ 6 , 7 ]. Despite this, many patients experience limited therapeutic benefit, and disease progression remains common in non-resectable CRC. Transarterial chemoembolization (TACE), widely used in hepatocellular carcinoma, has shown promise in treating CRC liver metastases and recurrent hepatic lesions post-surgery [ 8 , 9 ]. Lipiodol, an iodinated poppyseed oil, serves as an effective chemoembolization agent in other cancers, including breast and bladder, due to its tumor-selective retention and sustained drug release properties [ 10 , 11 ]. Preclinical studies using the VX2 rabbit colorectal tumor model have demonstrated the safety and efficacy of lipiodol-based chemoembolization [12]. However, clinical data on its application in primary CRC are scarce. This study aims to evaluate the safety and efficacy of transarterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization in patients with primary CRC who are ineligible for surgery. This regional interventional strategy may offer an alternative therapeutic option to enhance disease control and improve outcomes in this challenging patient population. 2. Methods 2.1 Study Design and Patient Enrollment This retrospective study analyzed clinical and treatment data from patients with advanced CRC who underwent trans-arterial infusion (TAI) chemotherapy combined with lipiodol chemoembolization. Collected data included patient demographics, comorbidities, tumor location and stage, metastatic sites, prior treatments (surgery, radiotherapy, or chemotherapy), embolized vessels, and treatment-related complications. All patients received TAI plus lipiodol chemoembolization once a month for 1 to 3 sessions. Clinical efficacy was assessed radiologically, and overall survival (OS) was calculated from the first intervention to death or last follow-up in February 2025. Eligible patients met the following criteria: (1) advanced CRC confirmed by imaging and biopsy; (2) ineligible for curative surgery due to unresectable disease, recurrence, or progression after first-/second-line or neoadjuvant therapies; (3) received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University; (4) ECOG performance status ≤ 2; and (5) life expectancy over 3 months. Patients were excluded if they were candidates for curative surgery or had not undergone the TAI-lipiodol procedure. 2.2 Pre-Procedure Evaluation All patients underwent thorough clinical and laboratory evaluation before each interventional session. This included complete blood count, liver and renal function tests, electrolytes, coagulation profile, tumor markers, and electrocardiography (ECG). Tumor vascularity, local invasion, and metastatic spread were assessed using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. Patients fasted for 6 hours and were restricted from fluid intake for 4 hours prior to treatment. Preoperative medications included gastric mucosal protectants, prophylactic antibiotics, and nutritional support. 2.3 TAI Combined with Lipiodol Chemoembolization Procedure All procedures were conducted in the digital subtraction angiography (DSA) suite at the First Affiliated Hospital of Zhengzhou University. With patients in the supine position under ECG monitoring and local anesthesia (2% lidocaine), the right femoral artery was punctured, and a 5F arterial sheath was placed. Using a 0.035-inch hydrophilic guidewire and 5F Cobra catheter (Cook), inferior mesenteric arteriography was performed to identify tumor-feeding vessels. A 2.7F microcatheter was then advanced to the proximal segment of the main tumor-supplying artery. For TAI, oxaliplatin (100 mg in 150 ml of 5% glucose) and raltitrexed (4 mg in 150 ml of 0.9% saline) were infused at 10 ml/min. Subsequently, the microcatheter was super-selectively advanced into tumor-feeding arteries. Under fluoroscopy, a lipiodol-doxorubicin emulsion (10 mg doxorubicin mixed with 10 ml lipiodol) was slowly administered to embolize the tumor vascular bed. Embolization continued until there was significant slowing or stasis of blood flow. 2.4 Post-Procedure Management Postoperative care included antibiotics, antiemetics, liver-protective agents, proton pump inhibitors, hydration, and other supportive therapies. One week after the procedure, liver and kidney function tests, blood counts, and electrolyte levels were repeated. Additional symptomatic treatments were provided as needed based on patient condition and clinical findings. 2.5 Tumor Response Evaluation and Follow-up Therapeutic response was assessed one month after each interventional session using contrast-enhanced CT or MRI. Tumor response was classified per RECIST version 1.0: complete response (CR) as the disappearance of all measurable lesions; partial response (PR) as tumor reduction > 50%; minor response as 25–50% reduction; stable disease (SD) as < 25% reduction without progression; and progressive disease (PD) as measurable tumor growth [ 13 ]. Patients achieving CR were evaluated for possible surgical resection or radiotherapy. Those with PR or SD continued receiving TAI plus lipiodol chemoembolization, while treatment was discontinued in cases of PD. Adverse events and complications were graded according to established criteria [ 14 ]. Follow-up was conducted every 1–3 months via outpatient visits or telephone interviews. Data collected included clinical status, symptom relief, tumor control (SD or PD), additional treatments (surgery or radiotherapy), and quality of life based on ECOG performance scores. Overall survival (OS) was calculated from the date of first intervention to death or last follow-up in February 2025. 2.6 Statistical analyses Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables were summarized as counts and percentages. Kaplan–Meier survival analysis was applied to estimate OS. A two-sided p-value less than 0.05 was considered statistically significant. 3. Results 3.1 Patient Characteristics and Baseline Clinical Profile A total of 239 patients with advanced or unresectable colorectal cancer were included in this study. The baseline demographic and clinical characteristics are summarized in Table 1 . The cohort consisted of 155 males (64.9%) and 84 females (35.1%), with a mean age of 60.5 ± 15.6 years. The most common tumor locations were the rectum (35.0%), followed by the sigmoid colon (27.2%), the junction of the rectum and sigmoid colon (13.4%), and the hepatic flexure of the colon (13.4%). Less frequently, tumors were located in the ileocecal region (7.9%) and the splenic flexure (2.5%). At diagnosis, 84 patients (35.1%) presented with distant metastasis, while 155 patients (64.9%) did not. Regarding prior treatments, the majority had received chemotherapy (62.3%), with a subset undergoing radiotherapy (21.8%) or radical surgery (7.9%) before the interventional procedure. Preoperative clinical symptoms were common, with abdominal discomfort (62.3%) being the most frequently reported, followed by exhaust defecation disorder (40.6%), hematochezia (32.6%), tenesmus (35.1%), and changes in bowel habits (18.8%). Patients underwent an average of 1.62 ± 0.59 sessions of transarterial infusion chemotherapy combined with lipiodol chemoembolization during the treatment course. Table 1 Characteristics of patients(N = 239) Characteristics n (percentage) Mean/median value Sex Male 155(64.9%) Female 84(35.1%) Age (years) 60.5 ± 15.6 Tumor location rectum 84(35.0%) Sigmoid colon 65(27.2%) Junction of rectum and sigmoid colon 32(13.4%) hepatic flexure of the colon 32(13.4%) Splenic flexure of colon 6(2.5%) ileocecal part of the colon 19(7.9%) Distant metastasis Yes 84(35.1%) No 155(64.9%) Preoperative treatment Radical surgery 19(7.9%) Chemotherapy 149(62.3%) Radiotherapy 52(21.8%) Preoperative clinical symptoms abdominal discomfort 149(62.3%) exhaust defecation disorder 97(40.6%) hematochezia 78(32.6%) Change in bowel habit 45(18.8%) tenesmus 84(35.1%) Times of interventional operations 1.62 ± 0.59 3.2 TAI Combined with Lipiodol Chemoembolization Demonstrates a Favorable Safety Profile with No Severe Perioperative Complications All 239 patients successfully underwent TAI combined with lipiodol chemoembolization, totaling 387 procedures. Notably, no severe perioperative complications were observed, including bowel perforation, ischemic necrosis, or procedure-related mortality. The procedures were well-tolerated, with no acute adverse events during the sessions. Super-selective angiography effectively identified tumor-feeding arteries in all cases. In 187 procedures, primary colorectal tumors were supplied by branches of the inferior mesenteric artery, including the colorectal, rectal, and sigmoid colon arteries. Another 52 procedures targeted right-sided colon lesions supplied by branches of the superior mesenteric artery. The mean lipiodol volume per procedure was 1.4 mL (range: 0.5–3 mL). Regarding treatment frequency, 103 patients received a single session, 123 underwent two sessions, and 12 had three sessions, typically at monthly intervals based on tumor response and symptom relief. Most post-procedural complications were mild to moderate and manageable. Nausea (Grade I–II) occurred in 65.1% (252/387) of procedures, abdominal discomfort in 38.2% (148/387), tenesmus in 39.8% (154/387), and myelosuppression (Grade I–III) in 46.8% (181/387). These symptoms responded well to supportive care, including symptomatic management and Kegel exercises. Mucinous stool was reported in 11.6% (45/387) of procedures within 1–3 days post-treatment, likely due to tumor necrosis and local exudation, with most cases resolving spontaneously. Hematochezia occurred in 4.9% (19/387) but was self-limiting. Procedural success is illustrated in Fig. 1 , featuring a 68-year-old female with advanced rectal cancer (T4N2M1). Pre-procedural DSA showed a hypervascular tumor bed with dense tumor-feeding vessels from the inferior mesenteric artery (Fig. 1 A). Post-procedural DSA confirmed complete disappearance of the tumor vascular blush, indicating effective embolization and successful occlusion of the tumor’s arterial supply (Fig. 1 B). These imaging findings visually validate the technical success and efficacy of the procedure. 3.3 High Objective Response and Disease Control Rates Observed Following TAI Combined with Lipiodol Chemoembolization Radiologic evaluations demonstrated robust tumor response following treatment. The disease control rate (DCR) was 94.6% (226/239), and the objective response rate (ORR), including complete and partial responses, was 59.4% (142/239), as shown in Table 2 . Imaging follow-up revealed significant reductions in tumor thickness and contrast enhancement, correlating with clinical improvements in abdominal discomfort, relief from defecation difficulties, and resolution of hematochezia in most patients. This is further supported by serial enhanced CT images, as shown in representative images in Fig. 2 , which document marked regression in rectal wall thickening and vascularity one month after treatment, compared to pre-treatment imaging. Table 2 The efficacy evaluation of patients Interventional therapy CR PR SD PD First 45 110 84 0 Second 26 65 32 13 Third 6 0 6 0 Complete response (CR); partial response (PR); stable disease (SD); progressive disease (PD). 3.4 Prolonged Overall Survival and Maintenance of Functional Status Following TAI Combined with Lipiodol Chemoembolization After embolization with lipiodol, abdominal discomfort, defecation and obstruction, and hematochezia symptoms were improved. During a median follow-up of 20.1 months (range, 4–77 months), 155 patients remained alive, with a mean survival of 21.8 months, while 84 patients had died, with a mean survival of 19.7 months. The median overall survival (OS) for the entire cohort was 21.7 months. Most surviving patients maintained an ECOG performance status of 0–1, reflecting good functional status post-treatment. Importantly, two patients achieved sufficient tumor regression to undergo radical surgical resection. Recurrence occurred in 84 patients, with 58 deaths due to tumor-related cachexia and 26 deaths from intestinal obstruction with septic shock. Despite this, the combination of TAI and lipiodol provided effective disease control and prolonged survival for a substantial proportion of patients with advanced CRC who were ineligible for surgery, as depicted in the Kaplan–Meier survival curve, as shown in Fig. 3 . 4. Discussion Patients with unresectable or advanced colorectal cancer (CRC) face limited therapeutic options. Current treatments, including systemic chemotherapy, radiotherapy, intraperitoneal hyperthermic perfusion, hormone replacement therapy, and immunotherapy, carry varying efficacy and toxicity profiles [ 15 – 18 ]. While chemotherapy and radiotherapy remain mainstays, both are associated with significant adverse effects. Chemotherapy-related complications such as thrombophlebitis, local tissue necrosis, and severe myelosuppression often lead to treatment discontinuation. Radiotherapy is similarly constrained by toxicities like radiation dermatitis and tissue injury. Hormone replacement therapy has shown some benefit in CRC prevention and survival improvement, though its mechanisms remain poorly defined [ 19 ]. Despite progress in locoregional therapies for CRC metastases, particularly in the liver and lungs, there is no consensus on interventional treatments for primary colorectal tumors [ 20 – 23 ]. Prior studies have shown that trans-arterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization can prolong survival in cancers such as breast and bladder [ 10 , 11 ]. This approach has also proven effective for CRC liver metastases, offering a favorable safety profile with minimal serious complications from lipiodol embolization [ 21 , 22 , 24 ]. However, its application in primary CRC remains underexplored. A significant proportion of advanced CRC patients present with or are at high risk for intestinal obstruction, limiting surgical options. The NCCN recommends palliative surgery, such as colostomy or bypass, for these patients. Many also suffer from chronic bleeding due to tumor surface ulceration or capillary erosion. Our study demonstrates that lipiodol chemoembolization effectively controls bleeding by targeting tumor vasculature, providing substantial symptom relief. Tumor shrinkage post-treatment also alleviates bowel obstruction, improving quality of life. This effect is partly due to lipiodol’s inherent macrovascular selectivity, as tumor vessels are typically larger and more fragile than normal vasculature. Additionally, intra-arterial chemotherapy induces vasoconstriction in normal arteries more readily than in tumor vessels, minimizing non-target embolization risks [ 8 ]. This selective mechanism ensures high local drug concentrations while sparing healthy tissue and reducing systemic toxicity. In our study, TAI combined with lipiodol chemoembolization delivered clear clinical benefits in primary CRC. Some patients developed transient tenesmus, likely from mucosal edema and nerve irritation, but these symptoms resolved with supportive care, including Kegel exercises. No cases of intestinal ischemia or perforation occurred, likely due to the super-selective embolization targeting tumor microvasculature rather than major feeding arteries. This approach offers significant technical advantages. Using a microcatheter and guidewire under fluoroscopic guidance enables precise, super-selective drug delivery directly to the tumor’s vascular bed. This achieves high local drug concentrations with minimal systemic exposure. Compared to systemic chemotherapy, lower doses are needed, reducing adverse effects [ 21 ]. Embolizing tumor-feeding vessels also prolongs drug retention within the tumor while cutting off its blood supply. Pharmacokinetic studies confirm that intra-arterial drug levels peak sharply at the tumor site, while systemic levels remain low [ 24 ]. Several procedural considerations optimize outcomes. First, accurate identification of tumor-supplying arteries is critical. Based on our experience, COBRA catheters outperform conventional RH and RLG catheters when navigating the inferior mesenteric artery, particularly via the contralateral internal iliac artery. Second, during chemotherapy infusion, over-selection of small branches should be avoided to prevent vasospasm, and the infusion rate should be maintained at ~ 10 mL/min. Third, embolization should target distal tumor-feeding branches, limiting it to the tumor vascular bed to reduce non-target embolization and preserve main arterial integrity. This study has limitations. It is a single-center retrospective analysis, which may limit generalizability. The lack of a randomized control group introduces potential selection bias. Additionally, the absence of genetic or molecular tumor profiling precluded personalized treatment adjustments. Nonetheless, the favorable safety profile, high disease control rate, and meaningful symptom relief underscore the potential of TAI combined with lipiodol chemoembolization as a palliative option for patients with advanced, unresectable CRC. This approach may serve as an effective alternative or adjunct to systemic therapy, particularly for patients with bleeding, bowel obstruction, or other debilitating symptoms. Future prospective, multicenter, randomized studies are needed to validate these findings. Integrating genomic profiling could further refine patient selection and optimize therapeutic outcomes. 5. Conclusions This study identifies trans-arterial infusion chemotherapy combined with lipiodol chemoembolization as a safe and effective palliative option for patients with advanced or unresectable colorectal cancer. The treatment offers meaningful tumor control, symptom relief, and prolonged survival with minimal serious complications. If validated in future prospective studies, this approach could serve as an important interventional strategy for patients ineligible for surgery or systemic therapy, reinforcing the role of locoregional treatments in comprehensive colorectal cancer care. Abbreviations CAPEOX, capecitabine and oxaliplatin; CR, complete response; CRC, colorectal cancer; CT, computed tomography; DCR, disease control rate; DSA, digital subtraction angiography; ECG, electrocardiography; ECOG, Eastern Cooperative Oncology Group; MRI, magnetic resonance imaging; ORR, objective response rate; OS, overall survival; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SPSS, Statistical Package for the Social Sciences; TAI, trans-arterial infusion chemotherapy; TACE, trans-arterial chemoembolization; VX2, virus-induced rabbit carcinoma cell line . Declarations Author Contributions J.Z. was responsible for conceptualization, data curation, and writing the original draft. X.G., Y.M., and M.Y. contributed to data curation and investigation. G.W. was involved in conceptualization, methodology, supervision, surgical procedures, and writing, review, and editing. All authors contributed to the interpretation of data, critically revised the manuscript for important intellectual content, and approved the final version for submission. Funding Information This work was supported by the First Affiliated Hospital of Zhengzhou University, which provided resources for patient recruitment, interventional procedures, data collection, and follow-up. No external funding was received from governmental, commercial, or not-for-profit organizations for this study. Conflict of interest statement The authors declare no conflicts of interest. Data Availability Statement The datasets generated and analyzed during this study are available from the corresponding author upon reasonable request. Ethics Statement This retrospective study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (Approval No. 2021-KY-0911-004). The requirement for informed consent was waived, as the study involved retrospective analysis of anonymized clinical data collected after patients or their guardians had provided written consent for treatment. Acknowledgments The authors sincerely thank their colleagues in the interventional operating room at the First Affiliated Hospital of Zhengzhou University for their technical support and assistance during the procedures. Authors’ Information J.Z. (Jiajia Zhang, MD) is a medical doctor at the Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University. Her clinical focus includes image-guided cancer therapies, with experience in performing and evaluating trans-arterial chemoembolization procedures. She played a central role in drafting the manuscript and coordinating data acquisition. ORCID: 0009-0001-3423-6252. X.G. (Xieyi Guo, MD) is affiliated with Zhengzhou University. He contributed to data collection and clinical coordination during the study and is pursuing further clinical research in gastrointestinal oncology and interventional procedures. Y.M. (Yishu Ma, MD) serves as a physician in the Department of Interventional Radiology at the First Affiliated Hospital of Zhengzhou University. Her expertise includes intra-arterial chemotherapy and post-procedural care in colorectal and hepatobiliary malignancies. She participated in patient treatment and data management. ORCID: 0009-0008-0116-0256. M.Y. (Meipan Yin, MD) is a clinician in the same department, specializing in minimally invasive therapies for gastrointestinal cancers. She assisted in data collection, patient follow-up, and treatment planning. ORCID: 0000-0002-0169-728X. G.W. (Gang Wu, MD) is a senior interventional radiologist at the First Affiliated Hospital of Zhengzhou University. 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Deschamps, Intra-arterial therapies for colorectal cancer liver metastases (radioembolization excluded), Bull Cancer, 104 (2017) 402-406. M.I. D'Angelica, C. Correa-Gallego, P.B. Paty, A. Cercek, A.N. Gewirtz, J.F. Chou, M. Capanu, T.P. Kingham, Y. Fong, R.P. DeMatteo, P.J. Allen, W.R. Jarnagin, N. Kemeny, Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes, Ann Surg, 261 (2015) 353-360. M.J. Swierz, D. Storman, R.P. Riemsma, R. Wolff, J.W. Mitus, M. Pedziwiatr, J. Kleijnen, M.M. Bala, Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases, Cochrane Database Syst Rev, 3 (2020) CD009498. R.M. O'Connell, E. Hoti, Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases, Cancers (Basel), 16 (2024). N. Chapelle, T. Matysiak-Budnik, F. Douane, S. Metairie, P. Rougier, Y. Touchefeu, Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives, Dig Liver Dis, 50 (2018) 220-225. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7035014","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":494953823,"identity":"7037d70b-7d46-49e5-9bdb-3579e173b4a7","order_by":0,"name":"Jiajia Zhang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Jiajia","middleName":"","lastName":"Zhang","suffix":""},{"id":494953824,"identity":"422695b7-3c3f-490b-b345-c4517596b93e","order_by":1,"name":"Xieyi Guo","email":"","orcid":"","institution":"Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xieyi","middleName":"","lastName":"Guo","suffix":""},{"id":494953825,"identity":"c16565d0-4d02-4b58-8bb8-feaae074bc64","order_by":2,"name":"Yishu Ma","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yishu","middleName":"","lastName":"Ma","suffix":""},{"id":494953826,"identity":"7c585fae-3b82-426a-af3e-f644c84838a8","order_by":3,"name":"Meipan Yin","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Meipan","middleName":"","lastName":"Yin","suffix":""},{"id":494953827,"identity":"aa754a58-d814-47e7-bac8-d250f97b6058","order_by":4,"name":"Gang Wu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABIElEQVRIiWNgGAWjYPCCAyCC8UGCAZscRICNOC3MBh8q+IxJ0sImOeOMXGIDIS0GN9Ivfi74dUfOnP3sAWneNrP0+f1nDBg+lB1m4J/dgENLTrH0zL5nxpY9eQnGvG1puY0NZwwYZ5w7zCBx5wBWLWY3chKkeXsOJ244kGOQzNt2LLeZsceAmbftMIOBRAIuLcm/gVrqN5x/Y3CYt+1/OhszjwHzX7xa0o9J8/w4nAB0oWHjjDNsCTxsQC2MeLTYn3nDZs3bcNhww403xgwfKtgMZ/CwFRzsOZfOI3EDuxbJ9vTHt3n+HJY3OJ9j/gMYlfLy/Yc3PvhRZi3HPwO7FgYGHgMGxjY0sQMgcRzqgYD9AQPDH9zSo2AUjIJRMAoYAHcQZQioOKRWAAAAAElFTkSuQmCC","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2025-07-03 06:53:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7035014/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7035014/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88526211,"identity":"d7718c01-2839-403f-93aa-440696fe5734","added_by":"auto","created_at":"2025-08-07 10:32:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":373031,"visible":true,"origin":"","legend":"\u003cp\u003eAngiographic images of a representative patient undergoing transarterial infusion chemotherapy combined with lipiodol chemoembolization. (A) Digital subtraction angiography (DSA) in a 68-year-old female with rectal cancer (T4N2M1) demonstrated a prominent tumor stain with a well-defined tumor vascular bed supplied by branches of the inferior mesenteric artery. A metal ring from an intrauterine device is visible on the right side. (B) Post-procedure DSA after superselective catheterization and delivery of 0.8 mL iodinated oil to the tumor vascular bed showed complete disappearance of the tumor stain, indicating effective embolization.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7035014/v1/96a614fa9778a2a0bb3423e4.png"},{"id":88526212,"identity":"a1a40ad2-1b98-41fc-a2d2-497ed89e9a59","added_by":"auto","created_at":"2025-08-07 10:32:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":582431,"visible":true,"origin":"","legend":"\u003cp\u003eContrast-enhanced CT images of the same patient before and after transarterial infusion chemotherapy combined with lipiodol chemoembolization. (A–C) Pre-procedure CT images demonstrate marked thickening of the sigmoid colon wall with significant contrast enhancement, consistent with rectal cancer. (D–F) Follow-up enhanced CT one month after the interventional procedure shows a notable reduction in rectal wall thickness and contrast enhancement, indicating effective tumor response to treatment\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7035014/v1/e024702518efaaa262118c95.png"},{"id":88527554,"identity":"0d86be2f-b06b-4bdf-b469-70eef63963fd","added_by":"auto","created_at":"2025-08-07 10:40:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":107385,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curve of overall survival (OS) in patients with advanced colorectal cancer treated with trans-arterial infusion chemotherapy combined with lipiodol chemoembolization. Cases are marked with “+” symbols. The x-axis represents OS in months, and the y-axis indicates cumulative survival.\u003c/p\u003e\n\u003cp\u003eThe median OS was 21.7 months. The curve shows a steady decline in survival, with a plateau beyond 36 months.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7035014/v1/cf76084811975c2150c7c02a.png"},{"id":107870192,"identity":"fe307cbc-454e-4415-95ff-e69d79e08231","added_by":"auto","created_at":"2026-04-27 07:39:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1339740,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7035014/v1/f00a77de-ac40-4ad6-b035-87b187dbce73.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSafety and Efficacy of trans-arterial Infusion Chemotherapy Combined with Lipiodol Chemoembolization for Advanced Colorectal Cancer: A Prospective Single-Center Clinical Study of 239 Patients in China\u003c/p\u003e","fulltext":[{"header":"1. Background","content":"\u003cp\u003eColorectal cancer (CRC) remains a significant global health burden, ranking third in incidence and second in mortality among all cancers worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Surgical resection is the cornerstone of curative treatment for localized CRC [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, 40\u0026ndash;50% of patients present with advanced disease and distant metastases, rendering them ineligible for surgery. Additionally, a considerable number experience recurrence after radical resection, have contraindications to surgery, or decline surgical options, leading to poor prognoses with a 5-year overall survival rate below 10% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. For patients unsuitable for surgery, systemic chemotherapy, typically fluoropyrimidine-based regimens such as FOLFOX or CAPEOX, is the standard first-line treatment. In selected cases, neoadjuvant chemotherapy enables tumor downstaging, allowing subsequent resection and improved survival outcomes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Despite this, many patients experience limited therapeutic benefit, and disease progression remains common in non-resectable CRC.\u003c/p\u003e\u003cp\u003eTransarterial chemoembolization (TACE), widely used in hepatocellular carcinoma, has shown promise in treating CRC liver metastases and recurrent hepatic lesions post-surgery [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Lipiodol, an iodinated poppyseed oil, serves as an effective chemoembolization agent in other cancers, including breast and bladder, due to its tumor-selective retention and sustained drug release properties [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Preclinical studies using the VX2 rabbit colorectal tumor model have demonstrated the safety and efficacy of lipiodol-based chemoembolization [12]. However, clinical data on its application in primary CRC are scarce. This study aims to evaluate the safety and efficacy of transarterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization in patients with primary CRC who are ineligible for surgery. This regional interventional strategy may offer an alternative therapeutic option to enhance disease control and improve outcomes in this challenging patient population.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study Design and Patient Enrollment\u003c/h2\u003e\u003cp\u003eThis retrospective study analyzed clinical and treatment data from patients with advanced CRC who underwent trans-arterial infusion (TAI) chemotherapy combined with lipiodol chemoembolization. Collected data included patient demographics, comorbidities, tumor location and stage, metastatic sites, prior treatments (surgery, radiotherapy, or chemotherapy), embolized vessels, and treatment-related complications. All patients received TAI plus lipiodol chemoembolization once a month for 1 to 3 sessions. Clinical efficacy was assessed radiologically, and overall survival (OS) was calculated from the first intervention to death or last follow-up in February 2025. Eligible patients met the following criteria: (1) advanced CRC confirmed by imaging and biopsy; (2) ineligible for curative surgery due to unresectable disease, recurrence, or progression after first-/second-line or neoadjuvant therapies; (3) received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University; (4) ECOG performance status\u0026thinsp;\u0026le;\u0026thinsp;2; and (5) life expectancy over 3 months. Patients were excluded if they were candidates for curative surgery or had not undergone the TAI-lipiodol procedure.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Pre-Procedure Evaluation\u003c/h2\u003e\u003cp\u003eAll patients underwent thorough clinical and laboratory evaluation before each interventional session. This included complete blood count, liver and renal function tests, electrolytes, coagulation profile, tumor markers, and electrocardiography (ECG). Tumor vascularity, local invasion, and metastatic spread were assessed using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. Patients fasted for 6 hours and were restricted from fluid intake for 4 hours prior to treatment. Preoperative medications included gastric mucosal protectants, prophylactic antibiotics, and nutritional support.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 TAI Combined with Lipiodol Chemoembolization Procedure\u003c/h2\u003e\u003cp\u003eAll procedures were conducted in the digital subtraction angiography (DSA) suite at the First Affiliated Hospital of Zhengzhou University. With patients in the supine position under ECG monitoring and local anesthesia (2% lidocaine), the right femoral artery was punctured, and a 5F arterial sheath was placed. Using a 0.035-inch hydrophilic guidewire and 5F Cobra catheter (Cook), inferior mesenteric arteriography was performed to identify tumor-feeding vessels. A 2.7F microcatheter was then advanced to the proximal segment of the main tumor-supplying artery. For TAI, oxaliplatin (100 mg in 150 ml of 5% glucose) and raltitrexed (4 mg in 150 ml of 0.9% saline) were infused at 10 ml/min. Subsequently, the microcatheter was super-selectively advanced into tumor-feeding arteries. Under fluoroscopy, a lipiodol-doxorubicin emulsion (10 mg doxorubicin mixed with 10 ml lipiodol) was slowly administered to embolize the tumor vascular bed. Embolization continued until there was significant slowing or stasis of blood flow.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Post-Procedure Management\u003c/h2\u003e\u003cp\u003ePostoperative care included antibiotics, antiemetics, liver-protective agents, proton pump inhibitors, hydration, and other supportive therapies. One week after the procedure, liver and kidney function tests, blood counts, and electrolyte levels were repeated. Additional symptomatic treatments were provided as needed based on patient condition and clinical findings.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Tumor Response Evaluation and Follow-up\u003c/h2\u003e\u003cp\u003eTherapeutic response was assessed one month after each interventional session using contrast-enhanced CT or MRI. Tumor response was classified per RECIST version 1.0: complete response (CR) as the disappearance of all measurable lesions; partial response (PR) as tumor reduction\u0026thinsp;\u0026gt;\u0026thinsp;50%; minor response as 25\u0026ndash;50% reduction; stable disease (SD) as \u0026lt;\u0026thinsp;25% reduction without progression; and progressive disease (PD) as measurable tumor growth [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients achieving CR were evaluated for possible surgical resection or radiotherapy. Those with PR or SD continued receiving TAI plus lipiodol chemoembolization, while treatment was discontinued in cases of PD. Adverse events and complications were graded according to established criteria [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Follow-up was conducted every 1\u0026ndash;3 months via outpatient visits or telephone interviews. Data collected included clinical status, symptom relief, tumor control (SD or PD), additional treatments (surgery or radiotherapy), and quality of life based on ECOG performance scores. Overall survival (OS) was calculated from the date of first intervention to death or last follow-up in February 2025.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Statistical analyses\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and categorical variables were summarized as counts and percentages. Kaplan\u0026ndash;Meier survival analysis was applied to estimate OS. A two-sided p-value less than 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Patient Characteristics and Baseline Clinical Profile\u003c/h2\u003e\u003cp\u003eA total of 239 patients with advanced or unresectable colorectal cancer were included in this study. The baseline demographic and clinical characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The cohort consisted of 155 males (64.9%) and 84 females (35.1%), with a mean age of 60.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6 years. The most common tumor locations were the rectum (35.0%), followed by the sigmoid colon (27.2%), the junction of the rectum and sigmoid colon (13.4%), and the hepatic flexure of the colon (13.4%). Less frequently, tumors were located in the ileocecal region (7.9%) and the splenic flexure (2.5%). At diagnosis, 84 patients (35.1%) presented with distant metastasis, while 155 patients (64.9%) did not. Regarding prior treatments, the majority had received chemotherapy (62.3%), with a subset undergoing radiotherapy (21.8%) or radical surgery (7.9%) before the interventional procedure. Preoperative clinical symptoms were common, with abdominal discomfort (62.3%) being the most frequently reported, followed by exhaust defecation disorder (40.6%), hematochezia (32.6%), tenesmus (35.1%), and changes in bowel habits (18.8%). Patients underwent an average of 1.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59 sessions of transarterial infusion chemotherapy combined with lipiodol chemoembolization during the treatment course.\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 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients(N\u0026thinsp;=\u0026thinsp;239)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (percentage)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean/median value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e155(64.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e84(35.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e60.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor location\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003erectum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e84(35.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSigmoid colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e65(27.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJunction of rectum and sigmoid colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32(13.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehepatic flexure of the colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32(13.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSplenic flexure of colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6(2.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eileocecal part of the colon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19(7.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistant metastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e84(35.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e155(64.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadical surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19(7.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e149(62.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e52(21.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative clinical symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eabdominal discomfort\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e149(62.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eexhaust defecation disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e97(40.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehematochezia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e78(32.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChange in bowel habit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45(18.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003etenesmus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e84(35.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTimes of interventional operations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2 TAI Combined with Lipiodol Chemoembolization Demonstrates a Favorable Safety Profile with No Severe Perioperative Complications\u003c/h2\u003e\u003cp\u003eAll 239 patients successfully underwent TAI combined with lipiodol chemoembolization, totaling 387 procedures. Notably, no severe perioperative complications were observed, including bowel perforation, ischemic necrosis, or procedure-related mortality. The procedures were well-tolerated, with no acute adverse events during the sessions. Super-selective angiography effectively identified tumor-feeding arteries in all cases. In 187 procedures, primary colorectal tumors were supplied by branches of the inferior mesenteric artery, including the colorectal, rectal, and sigmoid colon arteries. Another 52 procedures targeted right-sided colon lesions supplied by branches of the superior mesenteric artery. The mean lipiodol volume per procedure was 1.4 mL (range: 0.5\u0026ndash;3 mL). Regarding treatment frequency, 103 patients received a single session, 123 underwent two sessions, and 12 had three sessions, typically at monthly intervals based on tumor response and symptom relief.\u003c/p\u003e\u003cp\u003eMost post-procedural complications were mild to moderate and manageable. Nausea (Grade I\u0026ndash;II) occurred in 65.1% (252/387) of procedures, abdominal discomfort in 38.2% (148/387), tenesmus in 39.8% (154/387), and myelosuppression (Grade I\u0026ndash;III) in 46.8% (181/387). These symptoms responded well to supportive care, including symptomatic management and Kegel exercises. Mucinous stool was reported in 11.6% (45/387) of procedures within 1\u0026ndash;3 days post-treatment, likely due to tumor necrosis and local exudation, with most cases resolving spontaneously. Hematochezia occurred in 4.9% (19/387) but was self-limiting. Procedural success is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e, featuring a 68-year-old female with advanced rectal cancer (T4N2M1). Pre-procedural DSA showed a hypervascular tumor bed with dense tumor-feeding vessels from the inferior mesenteric artery (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Post-procedural DSA confirmed complete disappearance of the tumor vascular blush, indicating effective embolization and successful occlusion of the tumor\u0026rsquo;s arterial supply (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). These imaging findings visually validate the technical success and efficacy of the procedure.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3 High Objective Response and Disease Control Rates Observed Following TAI Combined with Lipiodol Chemoembolization\u003c/h2\u003e\u003cp\u003eRadiologic evaluations demonstrated robust tumor response following treatment. The disease control rate (DCR) was 94.6% (226/239), and the objective response rate (ORR), including complete and partial responses, was 59.4% (142/239), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Imaging follow-up revealed significant reductions in tumor thickness and contrast enhancement, correlating with clinical improvements in abdominal discomfort, relief from defecation difficulties, and resolution of hematochezia in most patients. This is further supported by serial enhanced CT images, as shown in representative images in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, which document marked regression in rectal wall thickening and vascularity one month after treatment, compared to pre-treatment imaging.\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 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe efficacy evaluation of patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInterventional therapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecond\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThird\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eComplete response (CR); partial response (PR); stable disease (SD); progressive disease (PD).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Prolonged Overall Survival and Maintenance of Functional Status Following TAI Combined with Lipiodol Chemoembolization\u003c/h2\u003e\u003cp\u003eAfter embolization with lipiodol, abdominal discomfort, defecation and obstruction, and hematochezia symptoms were improved. During a median follow-up of 20.1 months (range, 4\u0026ndash;77 months), 155 patients remained alive, with a mean survival of 21.8 months, while 84 patients had died, with a mean survival of 19.7 months. The median overall survival (OS) for the entire cohort was 21.7 months. Most surviving patients maintained an ECOG performance status of 0\u0026ndash;1, reflecting good functional status post-treatment. Importantly, two patients achieved sufficient tumor regression to undergo radical surgical resection. Recurrence occurred in 84 patients, with 58 deaths due to tumor-related cachexia and 26 deaths from intestinal obstruction with septic shock. Despite this, the combination of TAI and lipiodol provided effective disease control and prolonged survival for a substantial proportion of patients with advanced CRC who were ineligible for surgery, as depicted in the Kaplan\u0026ndash;Meier survival curve, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003ePatients with unresectable or advanced colorectal cancer (CRC) face limited therapeutic options. Current treatments, including systemic chemotherapy, radiotherapy, intraperitoneal hyperthermic perfusion, hormone replacement therapy, and immunotherapy, carry varying efficacy and toxicity profiles [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. While chemotherapy and radiotherapy remain mainstays, both are associated with significant adverse effects. Chemotherapy-related complications such as thrombophlebitis, local tissue necrosis, and severe myelosuppression often lead to treatment discontinuation. Radiotherapy is similarly constrained by toxicities like radiation dermatitis and tissue injury. Hormone replacement therapy has shown some benefit in CRC prevention and survival improvement, though its mechanisms remain poorly defined [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite progress in locoregional therapies for CRC metastases, particularly in the liver and lungs, there is no consensus on interventional treatments for primary colorectal tumors [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Prior studies have shown that trans-arterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization can prolong survival in cancers such as breast and bladder [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This approach has also proven effective for CRC liver metastases, offering a favorable safety profile with minimal serious complications from lipiodol embolization [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, its application in primary CRC remains underexplored.\u003c/p\u003e\u003cp\u003eA significant proportion of advanced CRC patients present with or are at high risk for intestinal obstruction, limiting surgical options. The NCCN recommends palliative surgery, such as colostomy or bypass, for these patients. Many also suffer from chronic bleeding due to tumor surface ulceration or capillary erosion. Our study demonstrates that lipiodol chemoembolization effectively controls bleeding by targeting tumor vasculature, providing substantial symptom relief. Tumor shrinkage post-treatment also alleviates bowel obstruction, improving quality of life. This effect is partly due to lipiodol\u0026rsquo;s inherent macrovascular selectivity, as tumor vessels are typically larger and more fragile than normal vasculature. Additionally, intra-arterial chemotherapy induces vasoconstriction in normal arteries more readily than in tumor vessels, minimizing non-target embolization risks [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This selective mechanism ensures high local drug concentrations while sparing healthy tissue and reducing systemic toxicity.\u003c/p\u003e\u003cp\u003eIn our study, TAI combined with lipiodol chemoembolization delivered clear clinical benefits in primary CRC. Some patients developed transient tenesmus, likely from mucosal edema and nerve irritation, but these symptoms resolved with supportive care, including Kegel exercises. No cases of intestinal ischemia or perforation occurred, likely due to the super-selective embolization targeting tumor microvasculature rather than major feeding arteries. This approach offers significant technical advantages. Using a microcatheter and guidewire under fluoroscopic guidance enables precise, super-selective drug delivery directly to the tumor\u0026rsquo;s vascular bed. This achieves high local drug concentrations with minimal systemic exposure. Compared to systemic chemotherapy, lower doses are needed, reducing adverse effects [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Embolizing tumor-feeding vessels also prolongs drug retention within the tumor while cutting off its blood supply. Pharmacokinetic studies confirm that intra-arterial drug levels peak sharply at the tumor site, while systemic levels remain low [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Several procedural considerations optimize outcomes. First, accurate identification of tumor-supplying arteries is critical. Based on our experience, COBRA catheters outperform conventional RH and RLG catheters when navigating the inferior mesenteric artery, particularly via the contralateral internal iliac artery. Second, during chemotherapy infusion, over-selection of small branches should be avoided to prevent vasospasm, and the infusion rate should be maintained at ~\u0026thinsp;10 mL/min. Third, embolization should target distal tumor-feeding branches, limiting it to the tumor vascular bed to reduce non-target embolization and preserve main arterial integrity.\u003c/p\u003e\u003cp\u003eThis study has limitations. It is a single-center retrospective analysis, which may limit generalizability. The lack of a randomized control group introduces potential selection bias. Additionally, the absence of genetic or molecular tumor profiling precluded personalized treatment adjustments.\u003c/p\u003e\u003cp\u003eNonetheless, the favorable safety profile, high disease control rate, and meaningful symptom relief underscore the potential of TAI combined with lipiodol chemoembolization as a palliative option for patients with advanced, unresectable CRC. This approach may serve as an effective alternative or adjunct to systemic therapy, particularly for patients with bleeding, bowel obstruction, or other debilitating symptoms. Future prospective, multicenter, randomized studies are needed to validate these findings. Integrating genomic profiling could further refine patient selection and optimize therapeutic outcomes.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis study identifies trans-arterial infusion chemotherapy combined with lipiodol chemoembolization as a safe and effective palliative option for patients with advanced or unresectable colorectal cancer. The treatment offers meaningful tumor control, symptom relief, and prolonged survival with minimal serious complications. If validated in future prospective studies, this approach could serve as an important interventional strategy for patients ineligible for surgery or systemic therapy, reinforcing the role of locoregional treatments in comprehensive colorectal cancer care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAPEOX, capecitabine and oxaliplatin; CR, complete response; CRC, colorectal cancer; CT, computed tomography; DCR, disease control rate; DSA, digital subtraction angiography; ECG, electrocardiography; ECOG, Eastern Cooperative Oncology Group; MRI, magnetic resonance imaging; ORR, objective response rate; OS, overall survival; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SPSS, Statistical Package for the Social Sciences; TAI, trans-arterial infusion chemotherapy; TACE, trans-arterial chemoembolization; VX2, virus-induced rabbit carcinoma cell line\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.Z. was responsible for conceptualization, data curation, and writing the original draft. X.G., Y.M., and M.Y. contributed to data curation and investigation. G.W. was involved in conceptualization, methodology, supervision, surgical procedures, and writing, review, and editing. All authors contributed to the interpretation of data, critically revised the manuscript for important intellectual content, and approved the final version for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the First Affiliated Hospital of Zhengzhou University, which provided resources for patient recruitment, interventional procedures, data collection, and follow-up. No external funding was received from governmental, commercial, or not-for-profit organizations for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (Approval No. 2021-KY-0911-004). The requirement for informed consent was waived, as the study involved retrospective analysis of anonymized clinical data collected after patients or their guardians had provided written consent for treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely thank their colleagues in the interventional operating room at the First Affiliated Hospital of Zhengzhou University for their technical support and assistance during the procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.Z. (Jiajia Zhang, MD) is a medical doctor at the Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University. Her clinical focus includes image-guided cancer therapies, with experience in performing and evaluating trans-arterial chemoembolization procedures. She played a central role in drafting the manuscript and coordinating data acquisition. ORCID: 0009-0001-3423-6252.\u003c/p\u003e\n\u003cp\u003eX.G. (Xieyi Guo, MD) is affiliated with Zhengzhou University. He contributed to data collection and clinical coordination during the study and is pursuing further clinical research in gastrointestinal oncology and interventional procedures.\u003c/p\u003e\n\u003cp\u003eY.M. (Yishu Ma, MD) serves as a physician in the Department of Interventional Radiology at the First Affiliated Hospital of Zhengzhou University. Her expertise includes intra-arterial chemotherapy and post-procedural care in colorectal and hepatobiliary malignancies. She participated in patient treatment and data management. ORCID: 0009-0008-0116-0256.\u003c/p\u003e\n\u003cp\u003eM.Y. (Meipan Yin, MD) is a clinician in the same department, specializing in minimally invasive therapies for gastrointestinal cancers. She assisted in data collection, patient follow-up, and treatment planning. ORCID: 0000-0002-0169-728X.\u003c/p\u003e\n\u003cp\u003eG.W. (Gang Wu, MD) is a senior interventional radiologist at the First Affiliated Hospital of Zhengzhou University. He has extensive experience in transcatheter oncologic therapies and led the study\u0026rsquo;s design and interventional procedures. He also supervised the manuscript revision process. ORCID: 0000-0002-7820-9408.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eF. Castro, C. Leite Pereira, M. Helena Macedo, A. Almeida, M. Jose Silveira, S. Dias, A. Patricia Cardoso, M. Jose Oliveira, B. Sarmento, Advances on colorectal cancer 3D models: The needed translational technology for nanomedicine screening, Adv Drug Deliv Rev, 175 (2021) 113824.\u003c/li\u003e\n\u003cli\u003eN. Baudoux, J. Meyer, A. Durham, C. Corro, F. Ris, I. Constantinescu, C. Bastid, T. 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Kelleher, Targeted therapy for recurrent breast carcinoma with regional \u0026apos;Lipiodol\u0026apos;/epirubicin infusion, Lancet, 336 (1990) 1383.\u003c/li\u003e\n\u003cli\u003eS. Ozono, E. Okajima, Y. Hirao, K. Babaya, S. Komada, H. Matsuki, S. Takahashi, H. Ohishi, T. Yoshioka, Transcatheter arterial embolization of vesical artery in the treatment of invasive bladder cancer, Eur Urol, 15 (1988) 176-179.\u003c/li\u003e\n\u003cli\u003eA. Nagamitsu, T. Konno, T. Oda, K. Tabaru, Y. Ishimaru, N. Kitamura, Targeted cancer chemotherapy for VX2 tumour implanted in the colon with lipiodol as a carrier, Eur J Cancer, 34 (1998) 1764-1769.\u003c/li\u003e\n\u003cli\u003eP.S. Turk, J.F. Belliveau, J.W. Darnowski, M.C. Weinberg, L. Leenen, H.J. Wanebo, Isolated pelvic perfusion for unresectable cancer using a balloon occlusion technique, Arch Surg, 128 (1993) 533-538; discussion 538-539.\u003c/li\u003e\n\u003cli\u003eE.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. 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Correa-Gallego, P.B. Paty, A. Cercek, A.N. Gewirtz, J.F. Chou, M. Capanu, T.P. Kingham, Y. Fong, R.P. DeMatteo, P.J. Allen, W.R. Jarnagin, N. Kemeny, Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes, Ann Surg, 261 (2015) 353-360.\u003c/li\u003e\n\u003cli\u003eM.J. Swierz, D. Storman, R.P. Riemsma, R. Wolff, J.W. Mitus, M. Pedziwiatr, J. Kleijnen, M.M. Bala, Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases, Cochrane Database Syst Rev, 3 (2020) CD009498.\u003c/li\u003e\n\u003cli\u003eR.M. O\u0026apos;Connell, E. Hoti, Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases, Cancers (Basel), 16 (2024).\u003c/li\u003e\n\u003cli\u003eN. Chapelle, T. Matysiak-Budnik, F. Douane, S. Metairie, P. Rougier, Y. Touchefeu, Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives, Dig Liver Dis, 50 (2018) 220-225.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorectal cancer, Trans-arterial infusion chemotherapy, Lipiodol chemoembolization, Interventional oncology, Advanced-stage cancer treatment","lastPublishedDoi":"10.21203/rs.3.rs-7035014/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7035014/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eAdvanced colorectal cancer (CRC) patients who are ineligible for surgery or have failed standard treatments face limited therapeutic options. Trans-arterial infusion chemotherapy (TAI) combined with lipiodol chemoembolization may offer a targeted, effective intervention to improve outcomes in this population.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eIn this prospective single-center study, 239 patients with advanced CRC received one to three sessions of intra-arterial infusion of oxaliplatin and raltitrexed, followed by embolization using a lipiodol-doxorubicin emulsion targeting tumor-feeding arteries. Treatment response was assessed using RECIST criteria. Safety, survival outcomes, and symptom relief were evaluated during follow-up. Descriptive and survival statistics were calculated using standard methods.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eThe disease control rate was 94.6%, with an objective response rate of 59.4%. Median overall survival was 21.7 months, and the mean follow-up duration was 20.1 months. Common adverse events included nausea (65.1%), abdominal discomfort (38.2%), tenesmus (39.8%), and myelosuppression (46.8%). All side effects were manageable with supportive care, and no serious perioperative complications such as intestinal necrosis or perforation occurred. Symptomatic relief was particularly notable in patients with tumor-related bleeding or obstruction. Most patients maintained a good performance status (ECOG 0\u0026ndash;1) throughout follow-up.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e\u003cp\u003eSuper selective TAI combined with lipiodol chemoembolization appears to be a safe and effective locoregional treatment strategy for patients with advanced CRC. It offers promising disease control, symptomatic relief, and survival benefit, with tolerable toxicity. These findings support further prospective, multicenter randomized trials to validate clinical utility and refine patient selection criteria.\u003c/p\u003e","manuscriptTitle":"Safety and Efficacy of trans-arterial Infusion Chemotherapy Combined with Lipiodol Chemoembolization for Advanced Colorectal Cancer: A Prospective Single-Center Clinical Study of 239 Patients in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 10:32:52","doi":"10.21203/rs.3.rs-7035014/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d9bcbd79-cfae-44f9-8db8-317a31137722","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-26T16:39:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-07 10:32:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7035014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7035014","identity":"rs-7035014","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}