The One-Stop Protocol: Immediate Tumor Visualization via TACE and Real-Time Ablation Guidance by CBCT in Synchronous MWA for Recurrent Small HCC

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The One-Stop Protocol: Immediate Tumor Visualization via TACE and Real-Time Ablation Guidance by CBCT in Synchronous MWA for Recurrent Small HCC | 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 The One-Stop Protocol: Immediate Tumor Visualization via TACE and Real-Time Ablation Guidance by CBCT in Synchronous MWA for Recurrent Small HCC Bin Yu, Peng Huang, Pengcheng Tian, Lin Xu, Yu Yin, Jun Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7173719/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 Objective To investigate the clinical efficacy and safety of transcatheter hepatic artery chemoembolization (TACE) combined with cone-beam computed tomography (CBCT)-guided microwave ablation (MWA) in the simultaneous treatment of recurrent small hepatocellular carcinoma (RsHCC). Materials and methods The clinical data of 60 patients who underwent TACE combined with CBCT-guided MWA synchronous treatment for RsHCC from March 2018 to December 2022 in our hospital were retrospectively analyzed. Follow-up was performed at 1, 3, 6, and 12 months after treatment. mRECIST criteria were used to assess the tumor response and analyze the objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS). Results The initial complete remission (CR) rate of TACE combined with CBCT-guided MWA synchronized treatment for RsHCC was 83.3% (50/60), with an initial ORR and DCR of 100%. The mean progression-free survival time was 37.90 (95%CI:27.10, 48.71) months, tumor progression occurred in 40% (24/60) of patients. Univariate and multivariate analyses showed that the maximum diameter of the tumor (≥ 2 cm and < 3 cm) was a major risk factor for PFS ( HR = 13.74, P = 0.001 ). No serious adverse events occurred in the study. Conclusions TACE combined with CBCT-guided MWA synchronization for the treatment of RsHCC is a highly effective and safe local treatment, especially suitable for lesions with limited conventional image guidance. Hepatocellular carcinoma Transarterial chemoembolization Cone-beam computed tomography Microwave ablation Figures Figure 1 Figure 2 Figure 3 Introduction Hepatocellular carcinoma (HCC) represents a malignancy characterized by high incidence, morbidity, and mortality [ 1 ] . According to BCLC guidelines, surgical resection remains the primary curative modality for early-stage HCC [ 2 ] . Nevertheless, patients undergoing resection continue to face substantial risks of recurrence and mortality, presenting significant challenges for post-resection management [ 3 – 5 ] . While liver transplantation constitutes the optimal therapy for recurrent small HCC (RsHCC), its application remains constrained by severe donor shortages and prohibitive costs [ 6 , 7 ] . Repeat surgical resection represents another preferred modality for recurrent HCC (RHCC). However, many patients are ineligible due to inadequate functional hepatic reserve or advanced cirrhosis. Local therapies—particularly TACE combined with ablation—have emerged as viable alternatives. While TACE monotherapy demonstrates limited tumor necrosis and high residual tumor recurrence, ablation achieves optimal outcomes in sub-3 cm HCC [ 8 , 9 ] . Synergistically, TACE-ablation combination therapy enhances tumor necrosis extent and improves survival versus monotherapy [ 10 – 13 ] . Conventional ultrasound/CT-guided ablation proves unsuitable for some RsHCC lesions with occult localization or poor visualization [ 14 ] . TACE enhances lesion conspicuity, enabling CBCT-guided targeting of otherwise undetectable tumors. Leveraging high-resolution 3D imaging and real-time navigation, CBCT serves as an advanced modality for complex ablations [ 15 ] . Consequently, we implemented TACE combined with CBCT-guided MWA synchronization in 60 RsHCC patients to evaluate this approach's clinical value and address conventional image-guidance limitations. 1 Information and methods 1.1 Study population Clinical data of patients who received TACE combined with CBCT-guided MWA synchronized treatment for RsHCC from March 2018 to December 2022 in the Department of Intervention of the First Affiliated Hospital of Soochow University were collected. Inclusion criteria for this study: 1. pathologically or clinically confirmed diagnosis of HCC (maximal diameter < 3 cm); 2. first recurrence after receiving surgical resection treatment; 3. conventional ultrasound/CT-guided ablation limitation; 4. number of hepatic tumors ≤ 3 and no extrahepatic metastasis as well as vascular invasion; 5. refusal of or unsuitable for re-surgical resection; 6. hepatic function Child-Pugh class A/B; 7. BCLC grading Stage A/B. Exclusion criteria: 1. patients with obvious contraindications to combined TACE and MWA therapy (e.g., inability to perform breath-holding, Child-Pugh grade C, severe ascites, platelet counts lower than 50,000/mm³ or 50×10 9 /L, or prothrombin activity < 50%); 2. patients combined with other antitumor therapies; and 3. patients with loss of follow-up or follow-up time of less than 1 year. This single-center retrospective study was approved by the Bioethics Committee of the First Affiliated Hospital of Soochow University, and informed consent was obtained from patients and their families. 1.2 Operation Procedure TACE treatment The TACE operation was performed by two interventionalists with more than 15 years of clinical experience. under local anesthesia, an arterial catheter sheath was inserted by the Seldinger puncture method, and a 4F RH catheter was applied to perform hepatic arteriography and CBCT hepatic arteriography, and the contrast injection rates were 4-6mL/s and 2-4mL/s, respectively. the tumor blood-supplying arteries were identified with the help of the embolism-guidance software. A 2.7 F microcatheter was super-selectively inserted into the tumor-supplying artery and chemoembolized with an emulsion of Oxaliplatin (85 mg/m 2 ) and Pirarubicin10-20 mg mixed with 10 ml of lipiodol, and the specific embolization dose was determined by the operator according to the size of the patient's tumor, and finally the embolization was strengthened with a small amount of 350–560µm gelatin sponge particles. With lipiodol can be seen in the portal vein segment, the tumor supplies arterial blood flow stasis as the embolic endpoint. Synchronized MWA Immediately after the TACE operation, a CBCT scan was performed to clarify the iodine oil deposition situation of the lesion, and the CT-like image was reconstructed by the workstation to set the target point and path of puncture, and then the MWA needle was guided to puncture the lesion in real time, and the ablation power was determined according to the location and size of the lesion. At the end of each ablation, the CBCT was reviewed in a timely manner, and the results were used to decide whether to perform additional ablations; if the ablation was satisfactory, the power was set at 55 W. The needle was withdrawn and the puncture tract was ablated. After the ablation, CBCT was immediately reviewed to observe the ablation range of the lesion, and the procedure was terminated when the ablation range exceeded the tumor margin by at least 0.5 cm and a ring-shaped edema band was visible. Finally, arteriography was performed to determine whether vascular-related injury had occurred. 1.3 Efficacy assessment Enhanced MRI was performed 1 month after surgery to assess the tumor response, and the patients' tumor indexes and imaging examinations were subsequently reviewed every 3 months. Patient survival was monitored during the follow-up period. The final follow-up date was December 31, 2022. Two radiologists with 10 years of experience in abdominal imaging evaluated postoperative MR images via PACS (NEUSOFTPACS/RIS, Shenyang Neusoft Co., Ltd.). The primary outcome observed was PFS. PFS was defined as the time from initiation of treatment to disease progression or death from any cause. Technical success was defined as successful completion of TACE combined with synchronized MWA in a single treatment session. The efficacy of tumor treatment was assessed at months 1, 3, 6, and 12 of follow-up according to the mRECIST criteria: complete response (CR); partial response (PR); progressive disease (PD) and stable disease (SD). Stable disease,SD). Objective response rate (ORR) was defined as complete remission (CR) + partial remission (PR), and disease control rate (DCR) was defined as complete remission (CR) + partial remission (PR) + stable disease (SD). Secondary outcomes included surgery-related complications and adverse events (Adverse Events, AEs) within 1 month after surgery, which were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). Surgery-related complications included abdominal hemorrhage, subcutaneous hematoma, arteriovenous fistula, pneumothorax, hemothorax, adjacent organ injury, bile duct stenosis, and liver abscess. Adverse events included post-embolization/ablation syndrome, hepatotoxicity, and systemic toxicity. Post-embolization/ablation syndrome was defined as the presence of fever, abdominal pain, vomiting, fatigue, bloating, nausea, hiccups, and constipation. Hepatotoxicity included elevated total bilirubin (TBIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, hepatic failure, hepatic encephalopathy, and hepatorenal syndrome. Systemic toxicity includes bone marrow suppression and granulocytopenia. Serious adverse events (SAEs) were defined as grade 3 or higher AEs. 1.4 Statistical analysis Statistical analysis was performed using SPSS 26.0, and continuous variables were expressed as mean ± standard deviation/median (interquartile spacing/range); grade variables were expressed as frequency (percentage). Cumulative progression-free survival and incidence of local tumor progression were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional risk model, and P < 0.05 was considered statistically significant. 2 Results 2.1 Baseline data This retrospective analysis evaluated patients with recurrent small hepatocellular carcinoma (RsHCC) deemed unsuitable for conventional image-guided ablation (2018-2022). Sixty patients meeting inclusion criteria underwent synchronous TACE/CBCT-guided MWA. Cohort characteristics: male predominance (83.3%, 50/60), mean age 59.4 ± 8.4 years, hepatitis B comorbidity (80.0%, 48/60), and predominantly BCLC-A stage (86.7%, 52/60). Comprehensive demographic and tumor characteristics are presented in Table 1. 2.2 Short-term efficacy Technical success was achieved in all 60 cases (100%). Complete lipiodol deposition was confirmed under fluoroscopic and CBCT guidance for every treated lesion. With follow-up through December 31, 2022, treatment response assessment demonstrated: the incidence of initial CR, PR, SD, and PD with combined synchronized therapy was 83.33% (50/60), 16.67% (10/60), 0, and 0, respectively, and its ORR and DCR reached 100% (60/60). 2.3 Progression-free survival During follow-up, disease progression occurred in 24 patients (40.0%), including 3 fatal cases. Mean progression-free survival (PFS) was 37.90 months (95% CI: 27.10–48.71). Multivariate analysis confirmed maximum tumor diameter (≥2 cm and <3 cm) as an independent predictor of reduced PFS (Table 2). 2.4 Safety analysis All patients underwent systematic postoperative hepatic function surveillance. Laboratory analyses revealed transient perturbations in liver enzymes and bilirubin metabolism: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) exhibited transient elevations. A characteristic early postoperative decline in serum albumin (ALB) was also observed. Through serial monitoring, all biochemical parameters normalized within two weeks post-procedure, with no cases of persistent hepatic impairment.. Fever and abdominal pain were the main postoperative adverse reactions, of which the incidence of fever was 58.33% (35/60), with 13.33% (8/60) of patients having a body temperature over 38°C; the incidence of abdominal pain was 38.33% (23/60), which manifested itself as mild symptoms. A total of 3 immediate complications were recorded during surgery, including 1 biliary reflex and 2 mild pneumothoraces. One delayed complication: reactive pleural effusion was identified during postoperative follow-up. All complications resolved effectively after prompt symptomatic management, and no serious adverse events (SAEs) occurred throughout the treatment. The specific adverse events and complications are shown in Table 3. 3 Discussion According to the Barcelona Clinic Liver Cancer (BCLC) guidelines, surgical resection represents the primary radical treatment option for early-stage HCC [2] . However, recent studies indicate that patients undergoing resection continue to face significant risks of high recurrence rates and mortality, posing a major challenge to post-resection management [5] . Liver transplantation is considered the optimal treatment for recurrent HCC but is severely limited by donor organ scarcity and high costs. Repeat surgical resection is also frequently precluded by inadequate residual liver function and advanced underlying cirrhosis. Consequently, determining optimal management strategies for recurrent HCC following initial surgical resection remains a critical unmet need in clinical practice. In recent years, local therapies—primarily transarterial chemoembolization (TACE) and ablation—have emerged as viable alternatives for recurrent HCC [16, 17] . TACE, a cornerstone treatment for intermediate-to-advanced HCC, combines embolization of tumor-feeding arteries with localized chemotherapy delivery to induce tumor necrosis. Technological advances now enable more precise embolization, minimizing functional liver impairment. However, TACE monotherapy may achieve incomplete tumor eradication. Local ablation therapy, an established curative modality for small HCC (sHCC), addresses this limitation [10, 11] . Studies demonstrate that combining TACE with ablation (e.g., microwave ablation [MWA] or radiofrequency ablation [RFA]) significantly improves survival in recurrent HCC patients with limited tumor burden (smaller or fewer lesions) compared to either modality alone [18, 19] . Thus, TACE-ablation combination therapy represents an effective local treatment strategy for recurrent HCC. However, precise ablation guidance via ultrasound or CT remains challenging for some recurrent small hepatocellular carcinomas (RsHCCs) due to occult lesion location or suboptimal visualization. While ultrasound-magnetic resonance fusion imaging has been developed to address sonographic limitations, 5%-13% of lesions still exhibit inadequate visualization [20, 21] . CT-guided ablation is similarly constrained for subdiaphragmatic/subcapsular HCC, where conventional ultrasound or CT often fails to establish safe needle trajectories. Furthermore, respiratory motion artifacts from inadequate breath-holding significantly compromise imaging quality in these cases [22] . Our study leveraged the synergistic potential of TACE combined with CBCT-guided MWA synchronization [23-25] : (1) Iodinated contrast enhancement: TACE delivers lipiodol to tumor vasculature, depositing within neoplastic tissue. Subsequent CBCT visualization facilitates precise MWA targeting; (2) Vascular modulation: Pre-ablation embolization mitigates the heat-sink effect by reducing tumor perfusion, enhancing thermal energy concentration during MWA. This vascular occlusion optimizes ablation efficacy; (3) Real-time navigation: CBCT's 3D reconstruction enables optimized needle trajectory planning, minimizing extrahepatic injury risk [26] . This synchronous approach achieved 83.3% (50/60) initial complete response (CR) in recurrent sHCC, with 100% objective response (ORR) and disease control rates (DCR), confirming high therapeutic efficacy. No major complications occurred, and transient liver function abnormalities normalized within 14 days post-procedure, indicating favorable safety. During follow-up, 24 patients experienced progression. Univariate/multivariate analyses identified maximum tumor diameter (≥2 cm and <3 cm) as the primary PFS risk factor ( HR=13.74, P=0.001 ). Tumor dimensions correlate positively with microvascular invasion (MVI) incidence (25% 4cm) [27] and peritumoral microsatellite prevalence, elevating recurrence probability. While TACE-MWA achieves local control, it cannot eradicate radiologically occult microsatellite lesions. Adjuvant systemic therapy (lenvatinib plus PD-1 blockade) may eliminate these micrometastases, potentiating treatment response [28] . Supporting this, Bowen et al. demonstrated significantly improved PFS with post-ablation adjuvant therapy [29] , suggesting combinatorial strategies with targeted immunotherapies should be explored for recurrent HCC with larger lesions to enhance long-term outcomes. Current literature predominantly employs staged TACE-MWA therapy (ablation delayed 1-2 weeks post-TACE). However, this approach may compromise efficacy due to: (1) HCC's complex vascular architecture, (2) potential post-TACE upregulation of pro-angiogenic factors, and (3) interval washout of lipiodol allowing lesion reconstitution - collectively increasing targeting uncertainty [8] . Our synchronous "one-stop" strategy circumvents these limitations without extending hospitalization or increasing complications versus staged protocols (Feng et al. [30] ). This integrated approach maximizes CBCT's dual-phase imaging capabilities [31, 32] : (1) Real-time procedural navigation: Enables millimeter-accurate ablation needle placement. (2) Single-contrast multiphase imaging: Early and delayed arterial phases acquired during TACE precisely delineate tumor morphology, vascular supply, and parenchymal relationships - enhancing target visualization while reducing diagnostic omissions. Consequently, synchronous TACE/CBCT-guided MWA demonstrates unique advantages over resection or monotherapies in recurrent sHCC, establishing a paradigm-shifting technical platform for precision locoregional therapy. This investigation has several constraints: 1.Its retrospective, single-center, single-arm design with limited sample size constrains statistical power and may introduce selection bias. 2.The abbreviated follow-up period precludes assessment of long-term survival benefits from synchronous therapy. Future multicenter randomized trials should validate these findings and evaluate combinatorial approaches incorporating immunotherapy or targeted agents. In conclusion, TACE combined with CBCT-guided MWA synchronous treatment demonstrates high efficacy and safety in treating RsHCC, particularly for lesions poorly visualized by conventional ultrasound or CT. This integrated approach represents a promising therapeutic alternative for technically challenging tumors. Declarations Ethical Statement : Ethics approval and consent to participate. The study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University, Suzhou, China (2024641, 11 November 2024). Prior to participation, each patient or their legal guardian provided written informed consent. All methods were performed in accordance with the relevant guidelinesand the Declaration of Helsinki. Funding: This work was supported by the National Natural Science Foundation of China Project [grant number 82272094]. Conflicts of Interest: The authors have all declared that they do not have any conflicts of interest. Author Contribution Statement:BinYu was responsible for writing the main paper, Pengcheng Tian and Lin Xu were responsible for the statistical analysis of the data, the remaining authors are responsible for reviewing the entire article. References HUANG D Q, SINGAL A G, KANWAL F, et al. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(12): 797-809. REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76(3): 681-693. KAWANO Y, SASAKI A, KAI S, et al. Prognosis of patients with intrahepatic recurrence after hepatic resection for hepatocellular carcinoma: a retrospective study[J]. 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YU M H, KIM J H, YOON J H, et al. Role of C-arm CT for transcatheter arterial chemoembolization of hepatocellular carcinoma: diagnostic performance and predictive value for therapeutic response compared with gadoxetic acid-enhanced MRI[J]. AJR Am J Roentgenol, 2013, 201(3): 675-683. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx 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. 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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-7173719","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":499939629,"identity":"a2464bdc-bb19-4bdd-af2d-d24f01a22819","order_by":0,"name":"Bin Yu","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Yu","suffix":""},{"id":499939632,"identity":"71b7f793-499e-46c9-9035-c99d9b4502fb","order_by":1,"name":"Peng Huang","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Huang","suffix":""},{"id":499939634,"identity":"8602188c-26c4-4ff3-97e3-c3351c721be2","order_by":2,"name":"Pengcheng Tian","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Pengcheng","middleName":"","lastName":"Tian","suffix":""},{"id":499939636,"identity":"a73f0737-da4b-44cb-a604-607fe03ee467","order_by":3,"name":"Lin Xu","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Xu","suffix":""},{"id":499939637,"identity":"0768d1b4-5d8d-4a6d-9253-320353ac9019","order_by":4,"name":"Yu Yin","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Yin","suffix":""},{"id":499939639,"identity":"84b45283-5334-4ce8-a295-064bf013acf0","order_by":5,"name":"Jun Yang","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Yang","suffix":""},{"id":499939641,"identity":"c78e5dd9-636c-4edd-9cc3-5e04db5927e3","order_by":6,"name":"Jiaan Ding","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Jiaan","middleName":"","lastName":"Ding","suffix":""},{"id":499939643,"identity":"e9076ee5-b075-4d2f-b25b-31d90bf1e337","order_by":7,"name":"Xiaoyun Miao","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyun","middleName":"","lastName":"Miao","suffix":""},{"id":499939644,"identity":"103bbc81-1def-4437-a6e1-a30e47f3b16a","order_by":8,"name":"Caifang Ni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYFCCA0BswMDAxgxiVDDwMDAwNj78QJQWtgQg4wxIC3OzsQRRtoG0MLaBWOxtAjx4FPI3nn3AXFBgJ8/Hxvzs4dd5h2XMQRolGOzkdBuwa5E4cNyAeYZBsmEbG5u5sey2wzyWDYxtDwoYko3NDmDXYsBwjIGZx+AAY5t8g5m05LY0ELvdQILhQOI2Alrs29jYv0lLzgFraZPgIUJLYhsbj5nkxwYbwlokDhxjOMxjkJwM1FImzXDMhseymREYyAa4/cI/4xjjY54/drbz29i3Sf6okbA3Z29/+PBDhZ0cLi1AaxjgUsyg6DBghjgYN+BvQLAZfxBQPApGwSgYBSMTAADHI1GbD0WKagAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":true,"prefix":"","firstName":"Caifang","middleName":"","lastName":"Ni","suffix":""}],"badges":[],"createdAt":"2025-07-21 06:08:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7173719/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7173719/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89266406,"identity":"3a1acd47-6ede-4528-a436-1cb66c76e715","added_by":"auto","created_at":"2025-08-18 08:15:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27082,"visible":true,"origin":"","legend":"\u003cp\u003e(A) PFS curves. (B) PFS curves according to independent risk factor groupings.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7173719/v1/1eac8d06fa9f4e241dfcf449.jpg"},{"id":89266404,"identity":"864c77d0-801c-499a-ac3e-ee561fb1d694","added_by":"auto","created_at":"2025-08-18 08:15:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50671,"visible":true,"origin":"","legend":"\u003cp\u003ePatient's liver function change graph. (A) Change in AST levels. (B) Change in ALT levels. (C) Change in TBIL levels. (D) Change in ALB levels.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7173719/v1/b24dd1c4423b57b088a0e205.jpg"},{"id":89268914,"identity":"3c9a1684-43ab-45bb-ac90-dd0df9240be8","added_by":"auto","created_at":"2025-08-18 08:31:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":76898,"visible":true,"origin":"","legend":"\u003cp\u003eMale patient, 61 years old, with a RsHCC nodule at the top of the hepatic diaphragm. (a) Preoperative enhanced MRI showed arterial phase hepatic diaphragm apical HCC nodule (white arrow) with a diameter of 18 mm; (b) Preoperative CT scanning suggested that the lesion was poorly displayed; (c) Embolization of hepatic artery was performed by using embolization navigation software to identify the tumor blood vessel supplying the tumor and perform hepatic arterial embolization; (d) Planning of the puncture path based on the CBCT images after the TACE treatment and performing the puncture navigation; (e) CBCT-guided MWA CBCT imaging performed after treatment showed a relatively low-density ring (white arrow) around the area of tumor iodine oil deposition; (f) Enhanced MRI performed at 3 months postoperatively suggested complete tumor necrosis.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7173719/v1/b25605f8235df311fde95f0a.jpg"},{"id":93896298,"identity":"a57ce6b3-e7ce-4122-b936-c1e4bf2d1b27","added_by":"auto","created_at":"2025-10-20 03:31:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":666590,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7173719/v1/bdb94212-e67a-49fe-b2a9-b81ff600f2e7.pdf"},{"id":89267711,"identity":"0804d310-c5b2-41f6-9670-422339be765f","added_by":"auto","created_at":"2025-08-18 08:23:28","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":22628,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7173719/v1/7239c06d81655810575d8cdd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The One-Stop Protocol: Immediate Tumor Visualization via TACE and Real-Time Ablation Guidance by CBCT in Synchronous MWA for Recurrent Small HCC","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) represents a malignancy characterized by high incidence, morbidity, and mortality\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. According to BCLC guidelines, surgical resection remains the primary curative modality for early-stage HCC\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, patients undergoing resection continue to face substantial risks of recurrence and mortality, presenting significant challenges for post-resection management\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. While liver transplantation constitutes the optimal therapy for recurrent small HCC (RsHCC), its application remains constrained by severe donor shortages and prohibitive costs \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRepeat surgical resection represents another preferred modality for recurrent HCC (RHCC). However, many patients are ineligible due to inadequate functional hepatic reserve or advanced cirrhosis. Local therapies\u0026mdash;particularly TACE combined with ablation\u0026mdash;have emerged as viable alternatives. While TACE monotherapy demonstrates limited tumor necrosis and high residual tumor recurrence, ablation achieves optimal outcomes in sub-3 cm HCC\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Synergistically, TACE-ablation combination therapy enhances tumor necrosis extent and improves survival versus monotherapy\u003csup\u003e[\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eConventional ultrasound/CT-guided ablation proves unsuitable for some RsHCC lesions with occult localization or poor visualization\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. TACE enhances lesion conspicuity, enabling CBCT-guided targeting of otherwise undetectable tumors. Leveraging high-resolution 3D imaging and real-time navigation, CBCT serves as an advanced modality for complex ablations\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Consequently, we implemented TACE combined with CBCT-guided MWA synchronization in 60 RsHCC patients to evaluate this approach's clinical value and address conventional image-guidance limitations.\u003c/p\u003e"},{"header":"1 Information and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e1.1 Study population\u003c/h2\u003e\u003cp\u003eClinical data of patients who received TACE combined with CBCT-guided MWA synchronized treatment for RsHCC from March 2018 to December 2022 in the Department of Intervention of the First Affiliated Hospital of Soochow University were collected. Inclusion criteria for this study: 1. pathologically or clinically confirmed diagnosis of HCC (maximal diameter\u0026thinsp;\u0026lt;\u0026thinsp;3 cm); 2. first recurrence after receiving surgical resection treatment; 3. conventional ultrasound/CT-guided ablation limitation; 4. number of hepatic tumors\u0026thinsp;\u0026le;\u0026thinsp;3 and no extrahepatic metastasis as well as vascular invasion; 5. refusal of or unsuitable for re-surgical resection; 6. hepatic function Child-Pugh class A/B; 7. BCLC grading Stage A/B. Exclusion criteria: 1. patients with obvious contraindications to combined TACE and MWA therapy (e.g., inability to perform breath-holding, Child-Pugh grade C, severe ascites, platelet counts lower than 50,000/mm\u0026sup3; or 50\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, or prothrombin activity\u0026thinsp;\u0026lt;\u0026thinsp;50%); 2. patients combined with other antitumor therapies; and 3. patients with loss of follow-up or follow-up time of less than 1 year. This single-center retrospective study was approved by the Bioethics Committee of the First Affiliated Hospital of Soochow University, and informed consent was obtained from patients and their families.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e1.2 Operation Procedure\u003c/h2\u003e\u003cp\u003eTACE treatment\u003c/p\u003e\u003cp\u003eThe TACE operation was performed by two interventionalists with more than 15 years of clinical experience. under local anesthesia, an arterial catheter sheath was inserted by the Seldinger puncture method, and a 4F RH catheter was applied to perform hepatic arteriography and CBCT hepatic arteriography, and the contrast injection rates were 4-6mL/s and 2-4mL/s, respectively. the tumor blood-supplying arteries were identified with the help of the embolism-guidance software. A 2.7 F microcatheter was super-selectively inserted into the tumor-supplying artery and chemoembolized with an emulsion of Oxaliplatin (85 mg/m\u003csup\u003e2\u003c/sup\u003e) and Pirarubicin10-20 mg mixed with 10 ml of lipiodol, and the specific embolization dose was determined by the operator according to the size of the patient's tumor, and finally the embolization was strengthened with a small amount of 350\u0026ndash;560\u0026micro;m gelatin sponge particles. With lipiodol can be seen in the portal vein segment, the tumor supplies arterial blood flow stasis as the embolic endpoint.\u003c/p\u003e\u003cp\u003eSynchronized MWA\u003c/p\u003e\u003cp\u003eImmediately after the TACE operation, a CBCT scan was performed to clarify the iodine oil deposition situation of the lesion, and the CT-like image was reconstructed by the workstation to set the target point and path of puncture, and then the MWA needle was guided to puncture the lesion in real time, and the ablation power was determined according to the location and size of the lesion. At the end of each ablation, the CBCT was reviewed in a timely manner, and the results were used to decide whether to perform additional ablations; if the ablation was satisfactory, the power was set at 55 W. The needle was withdrawn and the puncture tract was ablated. After the ablation, CBCT was immediately reviewed to observe the ablation range of the lesion, and the procedure was terminated when the ablation range exceeded the tumor margin by at least 0.5 cm and a ring-shaped edema band was visible. Finally, arteriography was performed to determine whether vascular-related injury had occurred.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e1.3 Efficacy assessment\u003c/h2\u003e\u003cp\u003eEnhanced MRI was performed 1 month after surgery to assess the tumor response, and the patients' tumor indexes and imaging examinations were subsequently reviewed every 3 months. Patient survival was monitored during the follow-up period. The final follow-up date was December 31, 2022. Two radiologists with 10 years of experience in abdominal imaging evaluated postoperative MR images via PACS (NEUSOFTPACS/RIS, Shenyang Neusoft Co., Ltd.).\u003c/p\u003e\u003cp\u003eThe primary outcome observed was PFS. PFS was defined as the time from initiation of treatment to disease progression or death from any cause. Technical success was defined as successful completion of TACE combined with synchronized MWA in a single treatment session. The efficacy of tumor treatment was assessed at months 1, 3, 6, and 12 of follow-up according to the mRECIST criteria: complete response (CR); partial response (PR); progressive disease (PD) and stable disease (SD). Stable disease,SD). Objective response rate (ORR) was defined as complete remission (CR)\u0026thinsp;+\u0026thinsp;partial remission (PR), and disease control rate (DCR) was defined as complete remission (CR)\u0026thinsp;+\u0026thinsp;partial remission (PR)\u0026thinsp;+\u0026thinsp;stable disease (SD).\u003c/p\u003e\u003cp\u003eSecondary outcomes included surgery-related complications and adverse events (Adverse Events, AEs) within 1 month after surgery, which were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). Surgery-related complications included abdominal hemorrhage, subcutaneous hematoma, arteriovenous fistula, pneumothorax, hemothorax, adjacent organ injury, bile duct stenosis, and liver abscess. Adverse events included post-embolization/ablation syndrome, hepatotoxicity, and systemic toxicity. Post-embolization/ablation syndrome was defined as the presence of fever, abdominal pain, vomiting, fatigue, bloating, nausea, hiccups, and constipation. Hepatotoxicity included elevated total bilirubin (TBIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, hepatic failure, hepatic encephalopathy, and hepatorenal syndrome. Systemic toxicity includes bone marrow suppression and granulocytopenia. Serious adverse events (SAEs) were defined as grade 3 or higher AEs.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e1.4 Statistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS 26.0, and continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation/median (interquartile spacing/range); grade variables were expressed as frequency (percentage). Cumulative progression-free survival and incidence of local tumor progression were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional risk model, and \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"2 Results","content":"\u003cp\u003e2.1 Baseline data\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis evaluated patients with recurrent small hepatocellular carcinoma (RsHCC) deemed unsuitable for conventional image-guided ablation (2018-2022). Sixty patients meeting inclusion criteria underwent synchronous TACE/CBCT-guided MWA. Cohort characteristics: male predominance (83.3%, 50/60), mean age 59.4 \u0026plusmn; 8.4 years, hepatitis B comorbidity (80.0%, 48/60), and predominantly BCLC-A stage (86.7%, 52/60). Comprehensive demographic and tumor characteristics are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e2.2 Short-term efficacy\u003c/p\u003e\n\u003cp\u003eTechnical success was achieved in all 60 cases (100%). Complete lipiodol deposition was confirmed under fluoroscopic and CBCT guidance for every treated lesion. With follow-up through December 31, 2022, treatment response assessment demonstrated: the incidence of initial CR, PR, SD, and PD with combined synchronized therapy was 83.33% (50/60), 16.67% (10/60), 0, and 0, respectively, and its ORR and DCR reached 100% (60/60).\u003c/p\u003e\n\u003cp\u003e2.3 Progression-free survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring follow-up, disease progression occurred in 24 patients (40.0%), including 3 fatal cases. Mean progression-free survival (PFS) was 37.90 months (95% CI: 27.10\u0026ndash;48.71). Multivariate analysis confirmed maximum tumor diameter (\u0026ge;2 cm and \u0026lt;3 cm) as an independent predictor of reduced PFS (Table 2).\u003c/p\u003e\n\u003cp\u003e2.4 Safety analysis\u003c/p\u003e\n\u003cp\u003eAll patients underwent systematic postoperative hepatic function surveillance. Laboratory analyses revealed transient perturbations in liver enzymes and bilirubin metabolism: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) exhibited transient elevations. A characteristic early postoperative decline in serum albumin (ALB) was also observed. Through serial monitoring, all biochemical parameters normalized within two weeks post-procedure, with no cases of persistent hepatic impairment..\u003c/p\u003e\n\u003cp\u003eFever and abdominal pain were the main postoperative adverse reactions, of which the incidence of fever was 58.33% (35/60), with 13.33% (8/60) of patients having a body temperature over 38\u0026deg;C; the incidence of abdominal pain was 38.33% (23/60), which manifested itself as mild symptoms. A total of 3 immediate complications were recorded during surgery, including 1 biliary reflex and 2 mild pneumothoraces. One delayed complication: reactive pleural effusion was identified during postoperative follow-up. All complications resolved effectively after prompt symptomatic management, and no serious adverse events (SAEs) occurred throughout the treatment. The specific adverse events and complications are shown in Table 3.\u003c/p\u003e"},{"header":"3 Discussion","content":"\u003cp\u003eAccording to the Barcelona Clinic Liver Cancer (BCLC) guidelines, surgical resection represents the primary radical treatment option for early-stage HCC\u003csup\u003e[2]\u003c/sup\u003e. However, recent studies indicate that patients undergoing resection continue to face significant risks of high recurrence rates and mortality, posing a major challenge to post-resection management\u003csup\u003e[5]\u003c/sup\u003e. Liver transplantation is considered the optimal treatment for recurrent HCC but is severely limited by donor organ scarcity and high costs. Repeat surgical resection is also frequently precluded by inadequate residual liver function and advanced underlying cirrhosis. Consequently, determining optimal management strategies for recurrent HCC following initial surgical resection remains a critical unmet need in clinical practice.\u003c/p\u003e\n\u003cp\u003eIn recent years, local therapies—primarily transarterial chemoembolization (TACE) and ablation—have emerged as viable alternatives for recurrent HCC\u003csup\u003e[16, 17]\u003c/sup\u003e. TACE, a cornerstone treatment for intermediate-to-advanced HCC, combines embolization of tumor-feeding arteries with localized chemotherapy delivery to induce tumor necrosis. Technological advances now enable more precise embolization, minimizing functional liver impairment. However, TACE monotherapy may achieve incomplete tumor eradication. Local ablation therapy, an established curative modality for small HCC (sHCC), addresses this limitation\u003csup\u003e[10, 11]\u003c/sup\u003e. Studies demonstrate that combining TACE with ablation (e.g., microwave ablation [MWA] or radiofrequency ablation [RFA]) significantly improves survival in recurrent HCC patients with limited tumor burden (smaller or fewer lesions) compared to either modality alone\u003csup\u003e[18, 19]\u003c/sup\u003e. Thus, TACE-ablation combination therapy represents an effective local treatment strategy for recurrent HCC.\u003c/p\u003e\n\u003cp\u003eHowever, precise ablation guidance via ultrasound or CT remains challenging for some recurrent small hepatocellular carcinomas (RsHCCs) due to occult lesion location or suboptimal visualization. While ultrasound-magnetic resonance fusion imaging has been developed to address sonographic limitations, 5%-13% of lesions still exhibit inadequate visualization\u003csup\u003e[20, 21]\u003c/sup\u003e. CT-guided ablation is similarly constrained for subdiaphragmatic/subcapsular HCC, where conventional ultrasound or CT often fails to establish safe needle trajectories. Furthermore, respiratory motion artifacts from inadequate breath-holding significantly compromise imaging quality in these cases\u003csup\u003e[22]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eOur study leveraged the synergistic potential of TACE combined with CBCT-guided MWA synchronization\u0026nbsp;\u003csup\u003e[23-25]\u003c/sup\u003e: (1) \u003cstrong\u003eIodinated contrast enhancement:\u003c/strong\u003e TACE delivers lipiodol to tumor vasculature, depositing within neoplastic tissue. Subsequent CBCT visualization facilitates precise MWA targeting; (2) \u003cstrong\u003eVascular modulation:\u003c/strong\u003e Pre-ablation embolization mitigates the heat-sink effect by reducing tumor perfusion, enhancing thermal energy concentration during MWA. This vascular occlusion optimizes ablation efficacy; (3)\u003cstrong\u003e\u0026nbsp;Real-time navigation:\u003c/strong\u003e CBCT's 3D reconstruction enables optimized needle trajectory planning, minimizing extrahepatic injury risk\u003csup\u003e[26]\u003c/sup\u003e. This synchronous approach achieved 83.3% (50/60) initial complete response (CR) in recurrent sHCC, with 100% objective response (ORR) and disease control rates (DCR), confirming high therapeutic efficacy. No major complications occurred, and transient liver function abnormalities normalized within 14 days post-procedure, indicating favorable safety. During follow-up, 24 patients experienced progression. Univariate/multivariate analyses identified maximum tumor diameter (≥2 cm and \u0026lt;3 cm) as the primary PFS risk factor (\u003cem\u003eHR=13.74, P=0.001\u003c/em\u003e). Tumor dimensions correlate positively with microvascular invasion (MVI) incidence (25% \u0026lt;2cm, 31% 2-4cm, 50% \u0026gt;4cm)\u003csup\u003e[27]\u003c/sup\u003e and peritumoral microsatellite prevalence, elevating recurrence probability. While TACE-MWA achieves local control, it cannot eradicate radiologically occult microsatellite lesions. Adjuvant systemic therapy (lenvatinib plus PD-1 blockade) may eliminate these micrometastases, potentiating treatment response\u003csup\u003e[28]\u003c/sup\u003e. Supporting this, Bowen et al. demonstrated significantly improved PFS with post-ablation adjuvant therapy\u003csup\u003e[29]\u003c/sup\u003e, suggesting combinatorial strategies with targeted immunotherapies should be explored for recurrent HCC with larger lesions to enhance long-term outcomes.\u003c/p\u003e\n\u003cp\u003eCurrent literature predominantly employs staged TACE-MWA therapy (ablation delayed 1-2 weeks post-TACE). However, this approach may compromise efficacy due to: (1) HCC's complex vascular architecture, (2) potential post-TACE upregulation of pro-angiogenic factors, and (3) interval washout of lipiodol allowing lesion reconstitution - collectively increasing targeting uncertainty\u003csup\u003e[8]\u003c/sup\u003e. Our synchronous \"one-stop\" strategy circumvents these limitations without extending hospitalization or increasing complications versus staged protocols (Feng et al.\u003csup\u003e[30]\u003c/sup\u003e). This integrated approach maximizes CBCT's dual-phase imaging capabilities\u003csup\u003e[31, 32]\u003c/sup\u003e: \u003cstrong\u003e(1) Real-time procedural navigation:\u003c/strong\u003e Enables millimeter-accurate ablation needle placement. \u003cstrong\u003e(2) Single-contrast multiphase imaging:\u003c/strong\u003e Early and delayed arterial phases acquired during TACE precisely delineate tumor morphology, vascular supply, and parenchymal relationships - enhancing target visualization while reducing diagnostic omissions. Consequently, synchronous TACE/CBCT-guided MWA demonstrates unique advantages over resection or monotherapies in recurrent sHCC, establishing a paradigm-shifting technical platform for precision locoregional therapy.\u003c/p\u003e\n\u003cp\u003eThis investigation has several constraints: 1.Its retrospective, single-center, single-arm design with limited sample size constrains statistical power and may introduce selection bias. 2.The abbreviated follow-up period precludes assessment of long-term survival benefits from synchronous therapy. Future multicenter randomized trials should validate these findings and evaluate combinatorial approaches incorporating immunotherapy or targeted agents.\u003c/p\u003e\n\u003cp\u003eIn conclusion, TACE combined with CBCT-guided MWA synchronous treatment demonstrates high efficacy and safety in treating RsHCC, particularly for lesions poorly visualized by conventional ultrasound or CT. This integrated approach represents a promising therapeutic alternative for technically challenging tumors.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Statement\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eEthics approval and consent to participate. The study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University, Suzhou, China (2024641, 11 November 2024). Prior to participation, each patient or their legal guardian provided written informed consent. All methods were performed in accordance with the relevant guidelinesand the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This work was supported by the National Natural Science Foundation of China Project [grant number 82272094].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors have all declared that they do not have any conflicts of interest.\u003c/p\u003e\u003cp\u003eAuthor Contribution Statement:BinYu was responsible for writing the main paper, Pengcheng Tian and Lin Xu were responsible for the statistical analysis of the data, the remaining authors are responsible for reviewing the entire article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHUANG D Q, SINGAL A G, KANWAL F, et al. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(12): 797-809.\u003c/li\u003e\n\u003cli\u003eREIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76(3): 681-693.\u003c/li\u003e\n\u003cli\u003eKAWANO Y, SASAKI A, KAI S, et al. Prognosis of patients with intrahepatic recurrence after hepatic resection for hepatocellular carcinoma: a retrospective study[J]. Eur J Surg Oncol, 2009, 35(2): 174-179.\u003c/li\u003e\n\u003cli\u003eMINAGAWA M, MAKUUCHI M, TAKAYAMA T, et al. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma[J]. Ann Surg, 2003, 238(5): 703-710.\u003c/li\u003e\n\u003cli\u003eFORNER A, REIG M, BRUIX J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314.\u003c/li\u003e\n\u003cli\u003eMARGARIT C, ESCARTIN A, CASTELLS L, et al. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation[J]. Liver Transpl, 2005, 11(10): 1242-1251.\u003c/li\u003e\n\u003cli\u003eDENG X, JIN Y, YANG W, et al. An Adrenal Hepatoid Adenocarcinoma with Left Renal Vein Thrombosis Extending into the Inferior Vena Cava[J]. Urol J, 2019, 16(5): 511-514.\u003c/li\u003e\n\u003cli\u003eLIN C C, CHENG Y T, CHEN M W, et al. The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2[J]. Liver Cancer, 2016, 5(1): 8-20.\u003c/li\u003e\n\u003cli\u003eDONG B, LIANG P, YU X, et al. Percutaneous sonographically guided microwave coagulation therapy for hepatocellular carcinoma: results in 234 patients[J]. AJR Am J Roentgenol, 2003, 180(6): 1547-1555.\u003c/li\u003e\n\u003cli\u003eCHEN R, GAN Y, GE N, et al. Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study[J]. J Vasc Interv Radiol, 2016, 27(12): 1829-1836.\u003c/li\u003e\n\u003cli\u003eKIM W, CHO S K, SHIN S W, et al. Combination therapy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma: comparison with TACE or RFA monotherapy[J]. Abdom Radiol (NY), 2019, 44(6): 2283-2292.\u003c/li\u003e\n\u003cli\u003eSUN Y, JI S, JI H, et al. Clinical efficacy analysis of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in primary liver cancer and recurrent liver cancer[J]. J BUON, 2019, 24(4): 1402-1407.\u003c/li\u003e\n\u003cli\u003eWANG C, LIAO Y, QIU J, et al. Transcatheter arterial chemoembolization alone or combined with ablation for recurrent intermediate-stage hepatocellular carcinoma: a propensity score matching study[J]. J Cancer Res Clin Oncol, 2020, 146(10): 2669-2680.\u003c/li\u003e\n\u003cli\u003eSMITS M L J, BRUIJNEN R C G, TETTEROO P, et al. Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) to Improve Tumor Visualization, Navigation and Margin Confirmation in Percutaneous Liver Tumor Ablation[J]. Cardiovasc Intervent Radiol, 2023, 46(10): 1365-1374.\u003c/li\u003e\n\u003cli\u003eLI Z, XU K, ZHOU X, et al. TACE sequential MWA guided by cone-beam computed tomography in the treatment of small hepatocellular carcinoma under the hepatic dome[J]. BMC Cancer, 2023, 23(1): 600.\u003c/li\u003e\n\u003cli\u003eZHANG X, LI C, WEN T, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern[J]. Eur J Gastroenterol Hepatol, 2015, 27(8): 933-940.\u003c/li\u003e\n\u003cli\u003eLIU Y, REN Y, GE S, et al. Transarterial Chemoembolization in Treatment-Naive and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome and Risk Signature Analysis[J]. Front Oncol, 2021, 11: 662408.\u003c/li\u003e\n\u003cli\u003eHIRAOKA A, KUMADA T, KUDO M, et al. Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis[J]. Dig Dis, 2017, 35(6): 602-610.\u003c/li\u003e\n\u003cli\u003ePENG Z W, ZHANG Y J, LIANG H H, et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial[J]. Radiology, 2012, 262(2): 689-700.\u003c/li\u003e\n\u003cli\u003eDONG Y, WANG W P, MAO F, et al. Application of imaging fusion combining contrast-enhanced ultrasound and magnetic resonance imaging in detection of hepatic cellular carcinomas undetectable by conventional ultrasound[J]. J Gastroenterol Hepatol, 2016, 31(4): 822-828.\u003c/li\u003e\n\u003cli\u003eCALANDRI M, MAURI G, YEVICH S, et al. Fusion Imaging and Virtual Navigation to Guide Percutaneous Thermal Ablation of Hepatocellular Carcinoma: A Review of the Literature[J]. Cardiovasc Intervent Radiol, 2019, 42(5): 639-647.\u003c/li\u003e\n\u003cli\u003eHEAD H W, DODD G D, 3RD, DALRYMPLE N C, et al. Percutaneous radiofrequency ablation of hepatic tumors against the diaphragm: frequency of diaphragmatic injury[J]. Radiology, 2007, 243(3): 877-884.\u003c/li\u003e\n\u003cli\u003eYAN L, REN Y, QIAN K, et al. Sequential transarterial chemoembolization and early radiofrequency ablation improves clinical outcomes for early-intermediate hepatocellular carcinoma in a 10-year single-center comparative study[J]. BMC Gastroenterol, 2021, 21(1): 182.\u003c/li\u003e\n\u003cli\u003eHASSANIN T M, FOUAD Y, HASSNINE A, et al. Quality of Life after Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Compared with Transcatheter Arterial Chemoembolization alone[J]. Asian Pac J Cancer Prev, 2021, 22(4): 1255-1261.\u003c/li\u003e\n\u003cli\u003eJIANG C, CHENG G, LIAO M, et al. Individual or combined transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma: a time-to-event meta-analysis[J]. World J Surg Oncol, 2021, 19(1): 81.\u003c/li\u003e\n\u003cli\u003eCHOO J Y, PARK C M, LEE N K, et al. Percutaneous transthoracic needle biopsy of small (\u0026lt;/= 1 cm) lung nodules under C-arm cone-beam CT virtual navigation guidance[J]. Eur Radiol, 2013, 23(3): 712-719.\u003c/li\u003e\n\u003cli\u003eXU X F, DIAO Y K, ZENG Y Y, et al. Association of severity in the grading of microvascular invasion with long-term oncological prognosis after liver resection for early-stage hepatocellular carcinoma: a multicenter retrospective cohort study from a hepatitis B virus-endemic area[J]. Int J Surg, 2023, 109(4): 841-849.\u003c/li\u003e\n\u003cli\u003eDONG Q, DIAO Y, SUN X, et al. Evaluation of tyrosine kinase inhibitors combined with antiprogrammed cell death protein 1 antibody in tyrosine kinase inhibitor-responsive patients with microsatellite stable/proficient mismatch repair metastatic colorectal adenocarcinoma: protocol for open-label, single-arm trial[J]. BMJ Open, 2022, 12(4): e049992.\u003c/li\u003e\n\u003cli\u003eMEN B, CUI H, HAN Z, et al. Evaluation of the efficacy of transarterial chemoembolization combined with microwave ablation followed by adjuvant therapy in patients with hepatocellular carcinoma[J]. Front Immunol, 2024, 15: 1337396.\u003c/li\u003e\n\u003cli\u003eFENG Y M, WANG X, WANG L, et al. Efficacy and safety of combination therapy of chemoembolization and radiofrequency ablation with different time intervals for hepatocellular carcinoma patients[J]. Surg Oncol, 2017, 26(3): 236-241.\u003c/li\u003e\n\u003cli\u003eFLORIDI C, RADAELLI A, ABI-JAOUDEH N, et al. C-arm cone-beam computed tomography in interventional oncology: technical aspects and clinical applications[J]. Radiol Med, 2014, 119(7): 521-532.\u003c/li\u003e\n\u003cli\u003eYU M H, KIM J H, YOON J H, et al. Role of C-arm CT for transcatheter arterial chemoembolization of hepatocellular carcinoma: diagnostic performance and predictive value for therapeutic response compared with gadoxetic acid-enhanced MRI[J]. AJR Am J Roentgenol, 2013, 201(3): 675-683.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\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":"Hepatocellular carcinoma, Transarterial chemoembolization, Cone-beam computed tomography, Microwave ablation","lastPublishedDoi":"10.21203/rs.3.rs-7173719/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7173719/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo investigate the clinical efficacy and safety of transcatheter hepatic artery chemoembolization (TACE) combined with cone-beam computed tomography (CBCT)-guided microwave ablation (MWA) in the simultaneous treatment of recurrent small hepatocellular carcinoma (RsHCC).\u003c/p\u003e\u003ch2\u003eMaterials and methods\u003c/h2\u003e\u003cp\u003eThe clinical data of 60 patients who underwent TACE combined with CBCT-guided MWA synchronous treatment for RsHCC from March 2018 to December 2022 in our hospital were retrospectively analyzed. Follow-up was performed at 1, 3, 6, and 12 months after treatment. mRECIST criteria were used to assess the tumor response and analyze the objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe initial complete remission (CR) rate of TACE combined with CBCT-guided MWA synchronized treatment for RsHCC was 83.3% (50/60), with an initial ORR and DCR of 100%. The mean progression-free survival time was 37.90 (95%CI:27.10, 48.71) months, tumor progression occurred in 40% (24/60) of patients. Univariate and multivariate analyses showed that the maximum diameter of the tumor (\u0026ge;\u0026thinsp;2 cm and \u0026lt;\u0026thinsp;3 cm) was a major risk factor for PFS (\u003cem\u003eHR\u0026thinsp;=\u0026thinsp;13.74, P\u0026thinsp;=\u0026thinsp;0.001\u003c/em\u003e). No serious adverse events occurred in the study.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eTACE combined with CBCT-guided MWA synchronization for the treatment of RsHCC is a highly effective and safe local treatment, especially suitable for lesions with limited conventional image guidance.\u003c/p\u003e","manuscriptTitle":"The One-Stop Protocol: Immediate Tumor Visualization via TACE and Real-Time Ablation Guidance by CBCT in Synchronous MWA for Recurrent Small HCC","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 08:15:24","doi":"10.21203/rs.3.rs-7173719/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":"bc0dc8cd-9451-4053-abe3-aadfe33696e3","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-20T03:23:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-18 08:15:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7173719","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7173719","identity":"rs-7173719","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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