Radioembolization of Primary Liver Tumors for Patients with Pre-Existing Ascites: Beyond Child-Pugh score

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Jabboure, Joshua A. Marlow, Wyatt D. Reed, Naganthan B. Mani, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7853339/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Abdominal Radiology → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose This study evaluates baseline characteristics associated with worsening ascites following TARE. A secondary objective was to examine survival among patients who developed ascites after TARE. Methods A total of 288 TARE deliveries (237 patients) for primary liver tumors were retrospectively reviewed. Imaging before and six months after TARE was assessed for ascites. Tumor volume, treated area, delivered activity, and liver function tests were reviewed. Logistic regression was performed for risk factors of liver decompensation including pre-existing ascites as a risk factor. Survival curves were plotted for overall survival. Results Mean (SD) age was 66 (11). 204 were male (71%). 266 (92%), 11 (4%), and 11 (4%) had hepatocellular carcinoma, intrahepatic cholangiocarcinoma and biphenotypic tumor, respectively. 60 (of 288, 21%) patients had pre-existing ascites. New/worsening ascites occurred in 121 (of 288, 42%) [93 (77%) new, 28 (23%) worsening]. Patients with new/worsening ascites had significantly greater increases in bilirubin (p = 0.01, p < 0.001). Pre-existing ascites was not associated with increased risk of post-TARE ascites progression, but a higher ALBI score was (OR = 2.89, p < 0.001). Neither perfused volume nor activity delivered predicted new/worsening ascites. Child-Pugh class (HR = 2.3, p < 0.001), pre-existing ascites (HR = 2, p < 0.001), ALBI score (HR = 1.5, p < 0.011) and new/worsening ascites (HR = 2.1, p < 0.001) were associated with lower survival. Conclusions Pre-existing ascites is associated with worse survival but should not preclude TARE. ALBI scoring can help distinguish patients at higher risk of post-TARE ascites. Liver hepatocellular carcinoma trans-arterial radioembolization ascites ALBI score Figures Figure 1 Figure 2 Figure 3 Key Points 1. Identifying patients at risk of new or worsening ascites after TARE is key to optimizing outcomes. 2. Pre-existing ascites alone was not associated with higher rates of post-TARE worsening ascites, but a higher baseline ALBI was. Both pre-existing and new/worsening ascites after TARE were associated with worse survival. 3. Identifying optimal candidates for TARE allows for safe and effective treatment. Patients with pre-existing ascites can still safely undergo TARE if ALBI score is favorable. Introduction Liver cancer is the third leading cause of cancer-related mortality globally [ 1 ], and it is often unresectable at the time of diagnosis [ 2 ]. Loco-regional therapies, such as transarterial radioembolization (TARE), play a critical role in reducing tumor burden and enhancing survival [ 3 , 4 ]. TARE has demonstrated the ability to prolong time to hepatic progression in primary liver tumors [ 5 ], but it does carry risks of adverse events, like radioembolization-induced liver disease (REILD) [ 6 ]. REILD is rare but can be associated with jaundice and ascites occurring in the first two months after TARE. Assessing hepatic toxicity of TARE can be challenging as it is usually performed in patients who have underlying liver disease and an intermediate to advanced tumor [ 6 ]. A study by Su et al. reviewing TARE for neuroendocrine tumors in 54 patients with non-cirrhotic livers found that 41% of those who received whole-liver radiation developed ascites, and 15% developed varices [ 7 ]. Fortunately, patients with primary liver tumors tend to have a more targeted focus of treatment and do not require whole-liver radiation. The presence of ascites prior to TARE has previously been identified as a negative prognostic factor for overall survival [ 8 – 11 ]. Given the risk of death without any treatment, certain patients with ascites will still receive TARE [ 2 ]. The influence of pre-existing ascites on mortality or worsened ascites following TARE remains uncertain. The primary objective of this study was to identify characteristics associated with worsening ascites following TARE. Pre-existing ascites was included as an independent risk factor. A secondary objective was to evaluate the survival of patients who develop new or worsening ascites after TARE. Methods Patient selection: This is a retrospective institutional review board-approved study compliant with the Health Insurance Portability and Accountability Act of 1996. Adult patients who underwent TARE for treatment of primary liver tumors between January 2013 and July of 2020 were included in this study. The decision to perform TARE was based on multidisciplinary board decision making. Patients with inadequate follow-up data and/or metastatic liver disease were excluded. A total of 288 TARE deliveries for 237 patients with primary liver tumors were included. Given a single patient could undergo TARE at different times, the number of encounters to treat lesions were used as the basis of calculations in the study. Patients who developed main portal vein thrombosis (PVT) or tumor progression after TARE were excluded from the analysis to reduce confounding factors that could influence the development of ascites or liver decompensation independent of the effects of TARE itself. Patients who underwent lobar conventional trans-arterial chemoembolization (cTACE) prior to TARE, were included in the study but analyzed separately. Data collection and definitions: Clinical notes, laboratory studies, and imaging were reviewed prior to TARE and throughout the treatment course until an end point of transplantation, death, or loss to follow-up. Most patients were evaluated with imaging approximately every 3 months after TARE for tumor progression. Ascites was evaluated by two investigators through a review of cross-sectional imaging obtained at the closest date prior to TARE and again at least six months following the procedure. Review for paracentesis performed at or around imaging time points was also used to assess for ascites. Ascites was graded mild if confined to the perihepatic space and moderate-severe if it extended beyond the perihepatic space. Overall survival and transplantation at follow up were collected. ALBI (Albumin-Bilirubin), MELD (model for end stage liver disease) and Child-Pugh scores were calculated and used in the regression model analysis. TARE Technique: Radioembolization with TheraSpheres (Boston Scientific, Marlborough, Massachusetts) was performed by 12 board-certified, fellowship-trained interventional radiologists with experience ranging from 1–20 years. TheraSpheres were prescribed based on the previously described standard protocol. Total tumor volume, baseline and follow-up laboratory values, other liver-directed therapies undertaken before TARE (including embolization or ablation) were evaluated. The number of treatments, total Y90 activity (GBq), and distribution of treated area in TARE were collected. Treated area was evaluated based on the angiograms and defined as lobar if delivery was via left or right hepatic arteries; segmental if delivery was via a segmental branch; divisional if delivery was via anterior or posterior division of the right hepatic artery. Statistics: The last date of follow-up was recorded as the date of death, transplantation, or last encounter with the patient. Logistic regression analysis was performed for the risk factors of ascites. Patients were censored at the time of transplant or at the date of last follow up for the Kaplan-Meier survival analysis. Cox regression analysis for predictors of survival. A 2-tailed Fisher exact test, Student t-test, and Mann-Whitney U test were used as appropriate to identify differences in patients with and without ascites. Data were analyzed using STATA version 17 software (StataCorp, College Station, Texas). A p value of < 0.05 was used as the threshold for statistical significance. Results Demographics: The mean (SD) age was 66 (11) years. 204 (of 288, 71%) patients were male. Of the 288 tumors, 266 (92%) were hepatocellular carcinoma (HCC), 11 (4%) were intrahepatic cholangiocarcinoma (IHC), and 11 (4%) were biphenotypic tumors. Median (IQR) tumor volume was 65mL (14–268). Mean (SD) total administered Y90 activity was 2.8 (1.5) GBq. The treated area was distributed as follows: lobar 104 (of 288, 70%), segmental 39 (of 288, 14%), and divisional 45 (of 288, 16%). Table 1 highlights baseline demographics and patient characteristics, comparing those with and without ascites before TARE. Table 1 , baseline characteristics of patient in the cohort, classified by if they developed ascites after TARE. Baseline characteristics WITHOUT new or worsening ascites after TARE (n = 167) WITH New or worsening ascites after TARE (n = 121) P-value Age – years 66 (64–68) 66 (64–68) 0.435 Male:Female (percent male) 108:59 (65%) 96:25 (79%) 0.007 Child-Pugh score 5.5 (5.4–5.7) 5.7 (5.7–5.9) 0.971 Bilirubin 0.75 (0.68–0.83) 0.92 (0.83-1.00) 0.005 Albumin 3.85 (3.76–3.93) 3.63 (3.55–3.72) 0.002 ALBI score -2.59 (-2.67 - -2.50) -2.33 (-2.42 - -2.25) 0.001 MELD 9.3 (8.9–9.7) 9.8 (9.2–10.3) 0.945 Lobar Y90 delivery 119 (71%) 84 (69%) 0.736 Mean total activity administered (GBq) 2.74 (2.48-3.00) 2.83 (2.59–3.08) 0.696 Baseline portal vein thrombosis (main or branch) 41 (25%) 42 (35%) 0.060 Liver Toxicity after TARE: Following TARE, total bilirubin increased from 0.8 to 2.3 mg/dL (p < 0.001) and alkaline phosphatase increased from159 to 212 U/L (p < 0.001). There was no significant increase in aminotransferase levels (ALT from 51 to 88, p = 0.206; AST from 69 to 180, p = 0.154). Comparing patients with and without pre-existing ascites, there was no significant difference in the rise of bilirubin (0.6 vs 0.3 mg/dL, p = 0.32). In patients without new/worsening ascites after TARE, bilirubin increased from 0.7 to 1.8 mg/dL (paired t-test, p < 0.001), whereas in those with new/worsening ascites after TARE bilirubin increased from 0.9 to 3.0 mg/dL (paired t-test, p < 0.001). The magnitude of increase in bilirubin was greater in patients who developed new/worsening ascites (p = 0.01). Similarly, MELD score increased significantly in all patients who received TARE, but the rise was greater in those who developed new/worsening ascites (2.2 vs. 5.9, p < 0.001). Ascites before and after TARE: At baseline, ascites was present in 60 (of 288, 21%) patients, with a majority classified as mild in severity [44 (of 60, 73%) mild ascites; 16 (of 60, 27%) moderate-severe ascites]. After TARE, 121 (of 288, 42%) developed new onset or worsening ascites. Among these, 93 (of 121, 77%) represented new onset ascites, while 28 (of 121, 23%) involved worsening of pre-existing ascites. Of the 121 patients with new/worsening ascites, 41 (34%) were classified as mild and 80 (66%) as moderate-severe. Illustrated by Fig. 1 , there was no significant difference in the incidence of new/worsening ascites after TARE when comparing patients with and without pre-existing ascites. The development of new onset ascites was observed in 93 (of 228, 41%), while worsening of pre-existing ascites was observed in 28 (of 60, 47%) (p = 0.412). In the patients who developed new/worsening ascites, 21 (of 121, 17%) experienced new onset hepatic encephalopathy, likely suggesting a more severe liver decompensation. Of these, 15 (of 21, 71%) had no ascites at baseline, while 6 (of 21, 29%) had pre-existing ascites. Risk Factors for Ascites after TARE Amongst the patients who developed new/worsening ascites, 96 (of 121, 79%) were male, and 25 (of 121, 21%) underwent prior lobar cTACE. Review of the entire cohort revealed PVT in 83 patients (of 288, 29%) before TARE, with branch PVT in 32 (of 288, 11%) and segmental PVT in 51 (of 288, 18%). There was no significant association between PVT and new/worsening ascites [PVT present at baseline versus absent: 42 (35%) and 79 (65%), p = 0.060]. Lobar TARE was performed in 203 cases (70%). Lobar delivery of TARE was not associated with the development of new/worsening ascites after treatment. [37 (of 85, 44%) non-lobar treatment vs. 84 (of 203, 41%) lobar treatment, p = 0.736]. Univariable and multivariable logistic regression analyses of baseline characteristics and the development of new/worsening ascites after TARE is presented in Table 2 . Factors such as PVT type, tumor volume, extent of Y90 infusion (segmental, divisional, lobar), total activity administered, Child-Pugh and MELD scores, baseline creatinine, INR, and alkaline phosphatase were not significantly associated with the development of new/worsening ascites after TARE. Multivariable analysis showed that pre-existing ascites was not associated with worsening ascites after TARE. However, male gender (OR = 2.1, p = 0.01), baseline albumin (OR = 0.4, p = 0.003), and ALBI score (OR = 2.89, p < 0.001) were all significantly associated with new/worsening ascites after TARE. Table 2 , Univariable and multivariable logistic regression analysis evaluating association between baseline characteristics and new/worsening ascites after TARE. HR (95%CI) P-value Univariable analysis Age – years 0.99 (0.98-1.00) 0.807 Sex (0 = male, 1 = female) 0.46 0.005 Child-Pugh score 1.24 0.088 Albumin 0.43 0.001 Bilirubin 1.8 0.017 ALBI score 2.6 < 0.001 MELD 1.06 0.143 Pre-existing ascites 1.26 0.410 Lobar Y90 delivery 0.92 0.765 Total Y90 activity (GBq) 1.03 0.888 Baseline portal vein thrombosis (0 = none, 1 = main portal, 2 = branch portal) 1.03 0.768 Total tumor volume 0.999 0.198 Multivariable analysis Age – years 0.99 (0.97–1.02) 0.770 Sex (0 = male, 1 = female) 0.54 (0.3–0.9) 0.032 ALBI score 3.7 (1.7-8) < 0.001 Pre-existing ascites 1.4 (0.58–3.4) 0.464 TARE = transarterial radioembolization, ALBI score = Albumin-Bilirubin score. Child-Pugh and ALBI Score Stratification: A majority (234, 86%) of patients had a baseline Child-Pugh A classification, while the remaining (38, 14%) were Child-Pugh B. At baseline, 118 (of 288, 41%) patients were classified as ALBI Grade I, while 161 (of 288, 56%) were ALBI Grade II (9 patients had missing values that precluded ALBI calculation). Patients who developed new/worsening ascites after TARE had significantly higher ALBI scores (-2.59 vs. -2.34, p = 0.0001). Among those with new/worsening ascites, 34 (of 121, 28%) were baseline ALBI grade 1, whereas 85 (of 121, 70%) were ALBI grade 2 (p < 0.001). Among patients with pre-existing ascites, 14 (of 60, 23%) classified as ALBI grade 1, while 45 (of 60, 75%) were ALBI grade 2 (p = 0.001). Within this group with pre-existing ascites, patients who experienced progression of ascites had significantly higher baseline ALBI grades [3 out of 14 (21%) in ALBI grade 1, versus 25 out of 45 (56%) in ALBI grade 2, p = 0.026]. Liver Transplant and Overall Survival Patients with pre-existing ascites had a median overall survival of 11 months (IQR: 5–33), compared to 24 months (IQR: 14-not reached) for those without pre-existing ascites (Logrank p < 0.001). There was no statistically significant difference in median survival between patients with baseline mild versus moderate-severe ascites (15 months vs. 7 months, Logrank, p = 0.247). (Fig. 2 ) Median overall survival was 27 months (IQR: 12-not-reached) for patients with baseline ALBI Grade 1 and 17 months (IQR: 5–46 months) for those with baseline ALBI Grade 2 (Logrank p = 0.001). In the subset of patients with pre-existing ascites, median overall survival was 27 months with baseline ALBI Grade I and 7 months with baseline ALBI Grade II (Logrank p = 0.001) Cox regression showed a decreased survival in patients who developed new/worsening ascites after TARE (HR = 2.1, p < 0.001) (Fig. 3 ). Multivariable Cox regression showed that Child-Pugh class (HR = 2.3, p < 0.001), pre-existing ascites (HR = 2, p < 0.001), and ALBI score (HR = 1.5, p < 0.011) were significantly associated with higher mortality. Following TARE, 41 (of 237, 17%) patients underwent liver transplant. This included 4 (10%) patients who had pre-existing ascites and 12 (29%) patients who experienced new/worsening ascites after TARE. Discussion Most patients who undergo TARE do not have ascites prior to receiving therapy [ 5 , 8 , 12 ]. This can be attributed to patients with clinically significant ascites often not having sufficient functional liver reserve to safely undergo TARE. However, as demonstrated by the 60 patients (21%) in this cohort, there are certain patients with pre-existing ascites who maintain adequate liver function to be considered eligible for TARE. Studies have shown that the presence of ascites prior to TARE can be associated with worse survival outcomes [ 8 , 10 , 11 ]. Consistent with previous studies, the presence of pre-existing ascites in this cohort, regardless of subsequent ascites progression, was a strong predictor of lower survival (11 vs 24 months, p < 0.001). New or worsening ascites after TARE was also independently associated with increased mortality (HR = 2.1, p < 0.001). Patients with pre-existing ascites already have a reduced overall survival at baseline, but with the increased mortality risk without treatment, TARE can still offer meaningful benefit. From a palliative perspective, it can help reduce tumor burden, alleviate symptoms, and prolong survival [ 10 ]. Notably, the incidence of new/worsening ascites after TARE was similar between patients with and without pre-existing ascites. This highlights the fact that a subset of patients with pre-existing ascites can safely undergo TARE, without increasing the risk of progression. TARE can also serve as a bridge to liver transplant [ 13 – 15 ]. In our cohort, 41 patients (17%) underwent liver transplant, including four patients with pre-existing ascites and 12 patients with new/worsening ascites after TARE. Selecting patients to safely undergo TARE requires a careful multi-disciplinary approach [ 2 ]. Previous studies have utilized traditional stratification methods, such as Child-Pugh and MELD, to demonstrate the influence of baseline liver function on survival after TARE [ 8 , 16 – 18 ]. Salem et al. reported a survival difference of 9.5 months in patients with baseline Child-Pugh A and Child-Pugh B scores [ 5 ]. This current study also corroborates with these findings, demonstrating that increased Child-Pugh scores are associated with higher mortality (HR = 2.3, p < 0.001). ALBI scoring has proven to be an effective tool for evaluating liver function and predicting outcomes in HCC patients undergoing tumor resection, cTACE, or TARE [ 2 , 19 – 24 ]. In this cohort, higher baseline ALBI grade was also strongly associated with lower overall survival (10-month median survival difference, p = 0.001). These associations held true in patients with pre-existing ascites (20-month median survival difference, p = 0.001). Additionally, while pre-existing ascites did not predict progression of ascites after TARE, ALBI score was significantly associated with new/worsening ascites. These findings suggest that ALBI scoring can offer a more nuanced stratification of TARE candidates including those with pre-existing ascites who are at risk for worsening ascites. This study has several limitations. This was a single center retrospective analysis. Due to the retrospective nature of the study, the evaluation of encephalopathy was limited. The study period encompasses older practice patterns, including more frequent use of lobar TARE. However, it is important to note that lobar treatment did not correlate with the development of ascites after TARE. Despite these limitations, the wide timespan of the study offers a more representative spectrum of disease and treatment approaches, enhancing the generalizability of the results to patients with primary liver tumors. The larger sample size and case-control design allows for meaningful conclusions to be drawn. In summary, while the presence of ascites before TARE is associated with worse survival outcomes, it should not preclude patients from receiving treatment. ALBI scoring can aid in making more informed decisions when selecting candidates for TARE, including patients with pre-existing ascites. Future multi-center prospective studies are needed to further validate these findings. Abbreviations Transarterial radioembolization (TARE), radioembolization-induced liver disease (REILD), portal vein thrombosis (PVT), conventional transarterial chemoembolization (cTACE), albumin-bilirubin (ALBI), model for end stage liver disease (MELD), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), Barcelona clinic liver cancer (BCLC) Declarations Author Contribution Fayez Jabboure and Nassir Rostambeigi contributed in data collection, design, writing and final editing. Naganathan Mani contributed in design and editing and data collection Joshua Marlow contributed in design and data collection and editing Wyatt Reed contributed in data collection and editing and design of the study. References Bray, F., et al., Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024. 74 (3): p. 229-263. 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Cite Share Download PDF Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Abdominal Radiology → Version 1 posted Editorial decision: Revision requested 10 Nov, 2025 Reviews received at journal 08 Nov, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviews received at journal 17 Oct, 2025 Reviewers agreed at journal 15 Oct, 2025 Reviewers invited by journal 15 Oct, 2025 Editor assigned by journal 14 Oct, 2025 Submission checks completed at journal 14 Oct, 2025 First submitted to journal 13 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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02:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7853339/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7853339/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00261-025-05336-6","type":"published","date":"2025-12-11T15:58:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94638764,"identity":"23c8f02c-e461-4d06-9e0a-04264e1da7e5","added_by":"auto","created_at":"2025-10-29 07:30:52","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":433529,"visible":true,"origin":"","legend":"","description":"","filename":"y90ascitesmanuscript101325AbdomRadiolBlinded.docx","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/e7ea7e3874a246ae5fe2d3be.docx"},{"id":94638763,"identity":"fc9bdd78-83ab-43f7-bcf5-0ebf0041c2de","added_by":"auto","created_at":"2025-10-29 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07:30:53","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74033,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/26a7ed0b28995d2f75af2f41.html"},{"id":94640662,"identity":"02d34067-eff3-4e4f-b8ef-18c6596d3d39","added_by":"auto","created_at":"2025-10-29 07:50:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11646,"visible":true,"origin":"","legend":"\u003cp\u003eNew or worsening ascites after TARE was similar in patients with and without pre-existing ascites (41% vs. 47%, p = 0.412).\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/3e3afd56dd3c103c5e4b526c.png"},{"id":94640318,"identity":"8abab957-a8da-4e43-8c2f-3a6e92990ecd","added_by":"auto","created_at":"2025-10-29 07:49:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21238,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves comparing patients with and without pre-existing ascites. Median overall survival was 24 months, 15 months, 7 months, if there was no, mild, or moderate/severe pre-existing ascites, respectively (Log-rank \u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/70a60701daafdc25c3641fe6.png"},{"id":94638760,"identity":"d966fe90-42c0-4042-a3e4-01bc6e5c14f9","added_by":"auto","created_at":"2025-10-29 07:30:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":18568,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves comparing patients who developed new or worsening ascites after TARE versus those without. Development of new or worsening ascites after TARE was associated with worse overall survival (HR=2.1, p \u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/0670e3cb84ff9d66cadc16e5.png"},{"id":98244899,"identity":"75172fe8-708c-4b3f-a08f-a0fd0301adaf","added_by":"auto","created_at":"2025-12-15 16:15:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":737463,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7853339/v1/7ab8f948-93d4-4c36-b2d2-42492b6915e4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Radioembolization of Primary Liver Tumors for Patients with Pre-Existing Ascites: Beyond Child-Pugh score ","fulltext":[{"header":"Key Points","content":"\u003cp\u003e1. Identifying patients at risk of new or worsening ascites after TARE is key to optimizing outcomes.\u003c/p\u003e\n\u003cp\u003e2. Pre-existing ascites alone was not associated with higher rates of post-TARE worsening ascites, but a higher baseline ALBI was. Both pre-existing and new/worsening ascites after TARE were associated with worse survival.\u003c/p\u003e\n\u003cp\u003e3. Identifying optimal candidates for TARE allows for safe and effective treatment. Patients with pre-existing ascites can still safely undergo TARE if ALBI score is favorable.\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eLiver cancer is the third leading cause of cancer-related mortality globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and it is often unresectable at the time of diagnosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Loco-regional therapies, such as transarterial radioembolization (TARE), play a critical role in reducing tumor burden and enhancing survival [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. TARE has demonstrated the ability to prolong time to hepatic progression in primary liver tumors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], but it does carry risks of adverse events, like radioembolization-induced liver disease (REILD) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. REILD is rare but can be associated with jaundice and ascites occurring in the first two months after TARE.\u003c/p\u003e\u003cp\u003eAssessing hepatic toxicity of TARE can be challenging as it is usually performed in patients who have underlying liver disease and an intermediate to advanced tumor [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A study by Su et al. reviewing TARE for neuroendocrine tumors in 54 patients with non-cirrhotic livers found that 41% of those who received whole-liver radiation developed ascites, and 15% developed varices [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Fortunately, patients with primary liver tumors tend to have a more targeted focus of treatment and do not require whole-liver radiation.\u003c/p\u003e\u003cp\u003eThe presence of ascites prior to TARE has previously been identified as a negative prognostic factor for overall survival [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Given the risk of death without any treatment, certain patients with ascites will still receive TARE [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The influence of pre-existing ascites on mortality or worsened ascites following TARE remains uncertain. The primary objective of this study was to identify characteristics associated with worsening ascites following TARE. Pre-existing ascites was included as an independent risk factor. A secondary objective was to evaluate the survival of patients who develop new or worsening ascites after TARE.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatient selection:\u003c/h2\u003e\u003cp\u003e This is a retrospective institutional review board-approved study compliant with the Health Insurance Portability and Accountability Act of 1996. Adult patients who underwent TARE for treatment of primary liver tumors between January 2013 and July of 2020 were included in this study. The decision to perform TARE was based on multidisciplinary board decision making. Patients with inadequate follow-up data and/or metastatic liver disease were excluded. A total of 288 TARE deliveries for 237 patients with primary liver tumors were included. Given a single patient could undergo TARE at different times, the number of encounters to treat lesions were used as the basis of calculations in the study. Patients who developed main portal vein thrombosis (PVT) or tumor progression after TARE were excluded from the analysis to reduce confounding factors that could influence the development of ascites or liver decompensation independent of the effects of TARE itself. Patients who underwent lobar conventional trans-arterial chemoembolization (cTACE) prior to TARE, were included in the study but analyzed separately.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection and definitions:\u003c/h3\u003e\n\u003cp\u003eClinical notes, laboratory studies, and imaging were reviewed prior to TARE and throughout the treatment course until an end point of transplantation, death, or loss to follow-up. Most patients were evaluated with imaging approximately every 3 months after TARE for tumor progression. Ascites was evaluated by two investigators through a review of cross-sectional imaging obtained at the closest date prior to TARE and again at least six months following the procedure. Review for paracentesis performed at or around imaging time points was also used to assess for ascites. Ascites was graded mild if confined to the perihepatic space and moderate-severe if it extended beyond the perihepatic space.\u003c/p\u003e\u003cp\u003eOverall survival and transplantation at follow up were collected. ALBI (Albumin-Bilirubin), MELD (model for end stage liver disease) and Child-Pugh scores were calculated and used in the regression model analysis.\u003c/p\u003e\n\u003ch3\u003eTARE Technique:\u003c/h3\u003e\n\u003cp\u003eRadioembolization with TheraSpheres (Boston Scientific, Marlborough, Massachusetts) was performed by 12 board-certified, fellowship-trained interventional radiologists with experience ranging from 1\u0026ndash;20 years. TheraSpheres were prescribed based on the previously described standard protocol.\u003c/p\u003e\u003cp\u003eTotal tumor volume, baseline and follow-up laboratory values, other liver-directed therapies undertaken before TARE (including embolization or ablation) were evaluated. The number of treatments, total Y90 activity (GBq), and distribution of treated area in TARE were collected. Treated area was evaluated based on the angiograms and defined as lobar if delivery was via left or right hepatic arteries; segmental if delivery was via a segmental branch; divisional if delivery was via anterior or posterior division of the right hepatic artery.\u003c/p\u003e\n\u003ch3\u003eStatistics:\u003c/h3\u003e\n\u003cp\u003eThe last date of follow-up was recorded as the date of death, transplantation, or last encounter with the patient. Logistic regression analysis was performed for the risk factors of ascites. Patients were censored at the time of transplant or at the date of last follow up for the Kaplan-Meier survival analysis. Cox regression analysis for predictors of survival. A 2-tailed Fisher exact test, Student t-test, and Mann-Whitney U test were used as appropriate to identify differences in patients with and without ascites. Data were analyzed using STATA version 17 software (StataCorp, College Station, Texas). A \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 was used as the threshold for statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDemographics:\u003c/h2\u003e\u003cp\u003eThe mean (SD) age was 66 (11) years. 204 (of 288, 71%) patients were male. Of the 288 tumors, 266 (92%) were hepatocellular carcinoma (HCC), 11 (4%) were intrahepatic cholangiocarcinoma (IHC), and 11 (4%) were biphenotypic tumors. Median (IQR) tumor volume was 65mL (14\u0026ndash;268). Mean (SD) total administered Y90 activity was 2.8 (1.5) GBq. The treated area was distributed as follows: lobar 104 (of 288, 70%), segmental 39 (of 288, 14%), and divisional 45 (of 288, 16%). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e highlights baseline demographics and patient characteristics, comparing those with and without ascites before TARE.\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\u003e, baseline characteristics of patient in the cohort, classified by if they developed ascites after TARE.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWITHOUT new or worsening ascites after TARE (n\u0026thinsp;=\u0026thinsp;167)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eWITH New or worsening ascites after TARE (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge \u0026ndash; years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66 (64\u0026ndash;68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (64\u0026ndash;68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.435\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale:Female \u003c/p\u003e\u003cp\u003e(percent male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108:59 (65%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e96:25 (79%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.5 (5.4\u0026ndash;5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.7 (5.7\u0026ndash;5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.971\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.75 (0.68\u0026ndash;0.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.92 (0.83-1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.85 (3.76\u0026ndash;3.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.63 (3.55\u0026ndash;3.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.59 (-2.67 - -2.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.33 (-2.42 - -2.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMELD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.3 (8.9\u0026ndash;9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.8 (9.2\u0026ndash;10.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.945\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLobar Y90 delivery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e119 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.736\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean total activity administered (GBq)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.74 (2.48-3.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.83 (2.59\u0026ndash;3.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.696\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline portal vein thrombosis (main or branch)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.060\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\n\u003ch3\u003eLiver Toxicity after TARE:\u003c/h3\u003e\n\u003cp\u003eFollowing TARE, total bilirubin increased from 0.8 to 2.3 mg/dL (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and alkaline phosphatase increased from159 to 212 U/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant increase in aminotransferase levels (ALT from 51 to 88, p\u0026thinsp;=\u0026thinsp;0.206; AST from 69 to 180, p\u0026thinsp;=\u0026thinsp;0.154). Comparing patients with and without pre-existing ascites, there was no significant difference in the rise of bilirubin (0.6 vs 0.3 mg/dL, p\u0026thinsp;=\u0026thinsp;0.32). In patients without new/worsening ascites after TARE, bilirubin increased from 0.7 to 1.8 mg/dL (paired t-test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas in those with new/worsening ascites after TARE bilirubin increased from 0.9 to 3.0 mg/dL (paired t-test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The magnitude of increase in bilirubin was greater in patients who developed new/worsening ascites (p\u0026thinsp;=\u0026thinsp;0.01). Similarly, MELD score increased significantly in all patients who received TARE, but the rise was greater in those who developed new/worsening ascites (2.2 vs. 5.9, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003ch3\u003eAscites before and after TARE:\u003c/h3\u003e\n\u003cp\u003eAt baseline, ascites was present in 60 (of 288, 21%) patients, with a majority classified as mild in severity [44 (of 60, 73%) mild ascites; 16 (of 60, 27%) moderate-severe ascites]. After TARE, 121 (of 288, 42%) developed new onset or worsening ascites. Among these, 93 (of 121, 77%) represented new onset ascites, while 28 (of 121, 23%) involved worsening of pre-existing ascites. Of the 121 patients with new/worsening ascites, 41 (34%) were classified as mild and 80 (66%) as moderate-severe.\u003c/p\u003e\u003cp\u003eIllustrated by Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, there was no significant difference in the incidence of new/worsening ascites after TARE when comparing patients with and without pre-existing ascites. The development of new onset ascites was observed in 93 (of 228, 41%), while worsening of pre-existing ascites was observed in 28 (of 60, 47%) (p\u0026thinsp;=\u0026thinsp;0.412).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn the patients who developed new/worsening ascites, 21 (of 121, 17%) experienced new onset hepatic encephalopathy, likely suggesting a more severe liver decompensation. Of these, 15 (of 21, 71%) had no ascites at baseline, while 6 (of 21, 29%) had pre-existing ascites.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eRisk Factors for Ascites after TARE\u003c/h2\u003e\u003cp\u003eAmongst the patients who developed new/worsening ascites, 96 (of 121, 79%) were male, and 25 (of 121, 21%) underwent prior lobar cTACE. Review of the entire cohort revealed PVT in 83 patients (of 288, 29%) before TARE, with branch PVT in 32 (of 288, 11%) and segmental PVT in 51 (of 288, 18%). There was no significant association between PVT and new/worsening ascites [PVT present at baseline versus absent: 42 (35%) and 79 (65%), p\u0026thinsp;=\u0026thinsp;0.060]. Lobar TARE was performed in 203 cases (70%). Lobar delivery of TARE was not associated with the development of new/worsening ascites after treatment. [37 (of 85, 44%) non-lobar treatment vs. 84 (of 203, 41%) lobar treatment, p\u0026thinsp;=\u0026thinsp;0.736].\u003c/p\u003e\u003cp\u003eUnivariable and multivariable logistic regression analyses of baseline characteristics and the development of new/worsening ascites after TARE is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Factors such as PVT type, tumor volume, extent of Y90 infusion (segmental, divisional, lobar), total activity administered, Child-Pugh and MELD scores, baseline creatinine, INR, and alkaline phosphatase were not significantly associated with the development of new/worsening ascites after TARE. Multivariable analysis showed that pre-existing ascites was not associated with worsening ascites after TARE. However, male gender (OR\u0026thinsp;=\u0026thinsp;2.1, p\u0026thinsp;=\u0026thinsp;0.01), baseline albumin (OR\u0026thinsp;=\u0026thinsp;0.4, p\u0026thinsp;=\u0026thinsp;0.003), and ALBI score (OR\u0026thinsp;=\u0026thinsp;2.89, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were all significantly associated with new/worsening ascites after TARE.\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\u003e, Univariable and multivariable logistic regression analysis evaluating association between baseline characteristics and new/worsening ascites after TARE.\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR (95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eUnivariable analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge \u0026ndash; years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.98-1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.807\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (0\u0026thinsp;=\u0026thinsp;male, 1\u0026thinsp;=\u0026thinsp;female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild-Pugh score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMELD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.143\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePre-existing ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.410\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLobar Y90 delivery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.765\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Y90 activity (GBq)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.888\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline portal vein thrombosis (0\u0026thinsp;=\u0026thinsp;none, 1\u0026thinsp;=\u0026thinsp;main portal, 2\u0026thinsp;=\u0026thinsp;branch portal)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.768\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal tumor volume\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.198\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMultivariable analysis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge \u0026ndash; years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.770\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (0\u0026thinsp;=\u0026thinsp;male, 1\u0026thinsp;=\u0026thinsp;female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.54 (0.3\u0026ndash;0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALBI score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.7 (1.7-8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePre-existing ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.4 (0.58\u0026ndash;3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.464\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eTARE\u0026thinsp;=\u0026thinsp;transarterial radioembolization, ALBI score\u0026thinsp;=\u0026thinsp;Albumin-Bilirubin score.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eChild-Pugh and ALBI Score Stratification:\u003c/h2\u003e\u003cp\u003eA majority (234, 86%) of patients had a baseline Child-Pugh A classification, while the remaining (38, 14%) were Child-Pugh B.\u003c/p\u003e\u003cp\u003eAt baseline, 118 (of 288, 41%) patients were classified as ALBI Grade I, while 161 (of 288, 56%) were ALBI Grade II (9 patients had missing values that precluded ALBI calculation). Patients who developed new/worsening ascites after TARE had significantly higher ALBI scores (-2.59 vs. -2.34, p\u0026thinsp;=\u0026thinsp;0.0001). Among those with new/worsening ascites, 34 (of 121, 28%) were baseline ALBI grade 1, whereas 85 (of 121, 70%) were ALBI grade 2 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eAmong patients with pre-existing ascites, 14 (of 60, 23%) classified as ALBI grade 1, while 45 (of 60, 75%) were ALBI grade 2 (p\u0026thinsp;=\u0026thinsp;0.001). Within this group with pre-existing ascites, patients who experienced progression of ascites had significantly higher baseline ALBI grades [3 out of 14 (21%) in ALBI grade 1, versus 25 out of 45 (56%) in ALBI grade 2, p\u0026thinsp;=\u0026thinsp;0.026].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eLiver Transplant and Overall Survival\u003c/h2\u003e\u003cp\u003ePatients with pre-existing ascites had a median overall survival of 11 months (IQR: 5\u0026ndash;33), compared to 24 months (IQR: 14-not reached) for those without pre-existing ascites (Logrank p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no statistically significant difference in median survival between patients with baseline mild versus moderate-severe ascites (15 months vs. 7 months, Logrank, p\u0026thinsp;=\u0026thinsp;0.247). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMedian overall survival was 27 months (IQR: 12-not-reached) for patients with baseline ALBI Grade 1 and 17 months (IQR: 5\u0026ndash;46 months) for those with baseline ALBI Grade 2 (Logrank p\u0026thinsp;=\u0026thinsp;0.001). In the subset of patients with pre-existing ascites, median overall survival was 27 months with baseline ALBI Grade I and 7 months with baseline ALBI Grade II (Logrank p\u0026thinsp;=\u0026thinsp;0.001)\u003c/p\u003e\u003cp\u003eCox regression showed a decreased survival in patients who developed new/worsening ascites after TARE (HR\u0026thinsp;=\u0026thinsp;2.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Multivariable Cox regression showed that Child-Pugh class (HR\u0026thinsp;=\u0026thinsp;2.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pre-existing ascites (HR\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and ALBI score (HR\u0026thinsp;=\u0026thinsp;1.5, p\u0026thinsp;\u0026lt;\u0026thinsp;0.011) were significantly associated with higher mortality.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFollowing TARE, 41 (of 237, 17%) patients underwent liver transplant. This included 4 (10%) patients who had pre-existing ascites and 12 (29%) patients who experienced new/worsening ascites after TARE.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eMost patients who undergo TARE do not have ascites prior to receiving therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This can be attributed to patients with clinically significant ascites often not having sufficient functional liver reserve to safely undergo TARE. However, as demonstrated by the 60 patients (21%) in this cohort, there are certain patients with pre-existing ascites who maintain adequate liver function to be considered eligible for TARE.\u003c/p\u003e\u003cp\u003eStudies have shown that the presence of ascites prior to TARE can be associated with worse survival outcomes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consistent with previous studies, the presence of pre-existing ascites in this cohort, regardless of subsequent ascites progression, was a strong predictor of lower survival (11 vs 24 months, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). New or worsening ascites after TARE was also independently associated with increased mortality (HR\u0026thinsp;=\u0026thinsp;2.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003ePatients with pre-existing ascites already have a reduced overall survival at baseline, but with the increased mortality risk without treatment, TARE can still offer meaningful benefit. From a palliative perspective, it can help reduce tumor burden, alleviate symptoms, and prolong survival [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, the incidence of new/worsening ascites after TARE was similar between patients with and without pre-existing ascites. This highlights the fact that a subset of patients with pre-existing ascites can safely undergo TARE, without increasing the risk of progression. TARE can also serve as a bridge to liver transplant [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our cohort, 41 patients (17%) underwent liver transplant, including four patients with pre-existing ascites and 12 patients with new/worsening ascites after TARE.\u003c/p\u003e\u003cp\u003eSelecting patients to safely undergo TARE requires a careful multi-disciplinary approach [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Previous studies have utilized traditional stratification methods, such as Child-Pugh and MELD, to demonstrate the influence of baseline liver function on survival after TARE [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Salem et al. reported a survival difference of 9.5 months in patients with baseline Child-Pugh A and Child-Pugh B scores [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This current study also corroborates with these findings, demonstrating that increased Child-Pugh scores are associated with higher mortality (HR\u0026thinsp;=\u0026thinsp;2.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eALBI scoring has proven to be an effective tool for evaluating liver function and predicting outcomes in HCC patients undergoing tumor resection, cTACE, or TARE [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In this cohort, higher baseline ALBI grade was also strongly associated with lower overall survival (10-month median survival difference, p\u0026thinsp;=\u0026thinsp;0.001). These associations held true in patients with pre-existing ascites (20-month median survival difference, p\u0026thinsp;=\u0026thinsp;0.001). Additionally, while pre-existing ascites did not predict progression of ascites after TARE, ALBI score was significantly associated with new/worsening ascites. These findings suggest that ALBI scoring can offer a more nuanced stratification of TARE candidates including those with pre-existing ascites who are at risk for worsening ascites.\u003c/p\u003e\u003cp\u003eThis study has several limitations. This was a single center retrospective analysis. Due to the retrospective nature of the study, the evaluation of encephalopathy was limited. The study period encompasses older practice patterns, including more frequent use of lobar TARE. However, it is important to note that lobar treatment did not correlate with the development of ascites after TARE. Despite these limitations, the wide timespan of the study offers a more representative spectrum of disease and treatment approaches, enhancing the generalizability of the results to patients with primary liver tumors. The larger sample size and case-control design allows for meaningful conclusions to be drawn.\u003c/p\u003e\u003cp\u003eIn summary, while the presence of ascites before TARE is associated with worse survival outcomes, it should not preclude patients from receiving treatment. ALBI scoring can aid in making more informed decisions when selecting candidates for TARE, including patients with pre-existing ascites. Future multi-center prospective studies are needed to further validate these findings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTransarterial radioembolization (TARE), radioembolization-induced liver disease (REILD), portal vein thrombosis (PVT), conventional transarterial chemoembolization (cTACE), albumin-bilirubin (ALBI), model for end stage liver disease (MELD), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), Barcelona clinic liver cancer (BCLC)\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eFayez Jabboure and Nassir Rostambeigi contributed in data collection, design, writing and final editing. Naganathan Mani contributed in design and editing and data collection Joshua Marlow contributed in design and data collection and editing Wyatt Reed contributed in data collection and editing and design of the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray, F., et al., \u003cem\u003eGlobal cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\u003c/em\u003e CA Cancer J Clin, 2024. \u003cstrong\u003e74\u003c/strong\u003e(3): p. 229-263.\u003c/li\u003e\n\u003cli\u003eReig, M., et al., \u003cem\u003eBCLC strategy for prognosis prediction and treatment recommendation: The 2022 update.\u003c/em\u003e J Hepatol, 2022. \u003cstrong\u003e76\u003c/strong\u003e(3): p. 681-693.\u003c/li\u003e\n\u003cli\u003eSalem, R., et al., \u003cem\u003eYttrium-90 microspheres: radiation therapy for unresectable liver cancer.\u003c/em\u003e J Vasc Interv Radiol, 2002. \u003cstrong\u003e13\u003c/strong\u003e(9 Pt 2): p. S223-9.\u003c/li\u003e\n\u003cli\u003eD\u0026apos;Avola, D., et al., \u003cem\u003eA retrospective comparative analysis of the effect of Y90-radioembolization on the survival of patients with unresectable hepatocellular carcinoma.\u003c/em\u003e Hepatogastroenterology, 2009. \u003cstrong\u003e56\u003c/strong\u003e(96): p. 1683-8.\u003c/li\u003e\n\u003cli\u003eSalem, R., et al., \u003cem\u003eRadioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes.\u003c/em\u003e Gastroenterology, 2010. \u003cstrong\u003e138\u003c/strong\u003e(1): p. 52-64.\u003c/li\u003e\n\u003cli\u003eCurrie, B.M., et al., \u003cem\u003eRadioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis.\u003c/em\u003e J Vasc Interv Radiol, 2019. \u003cstrong\u003e30\u003c/strong\u003e(12): p. 1915-1923.\u003c/li\u003e\n\u003cli\u003eSu, Y.K., et al., \u003cem\u003eLong-Term Hepatotoxicity of Yttrium-90 Radioembolization as Treatment of Metastatic Neuroendocrine Tumor to the Liver.\u003c/em\u003e J Vasc Interv Radiol, 2017. \u003cstrong\u003e28\u003c/strong\u003e(11): p. 1520-1526.\u003c/li\u003e\n\u003cli\u003eAbouchaleh, N., et al., \u003cem\u003e(90)Y Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort.\u003c/em\u003e J Nucl Med, 2018. \u003cstrong\u003e59\u003c/strong\u003e(7): p. 1042-1048.\u003c/li\u003e\n\u003cli\u003eTomozawa, Y., et al., \u003cem\u003eLong-Term Toxicity after Transarterial Radioembolization with Yttrium-90 Using Resin Microspheres for Neuroendocrine Tumor Liver Metastases.\u003c/em\u003e J Vasc Interv Radiol, 2018. \u003cstrong\u003e29\u003c/strong\u003e(6): p. 858-865.\u003c/li\u003e\n\u003cli\u003eHelmberger, T., et al., \u003cem\u003eClinical Application of Trans-Arterial Radioembolization in Hepatic Malignancies in Europe: First Results from the Prospective Multicentre Observational Study CIRSE Registry for SIR-Spheres Therapy (CIRT).\u003c/em\u003e Cardiovasc Intervent Radiol, 2021. \u003cstrong\u003e44\u003c/strong\u003e(1): p. 21-35.\u003c/li\u003e\n\u003cli\u003eMantry, P.S., et al., \u003cem\u003eSelective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study.\u003c/em\u003e J Gastrointest Oncol, 2017. \u003cstrong\u003e8\u003c/strong\u003e(5): p. 799-807.\u003c/li\u003e\n\u003cli\u003eYim, S.Y., et al., \u003cem\u003eTransarterial Radioembolization for Unresectable Hepatocellular Carcinoma: Real-Life Efficacy and Safety Analysis of Korean Patients.\u003c/em\u003e Cancers (Basel), 2022. \u003cstrong\u003e14\u003c/strong\u003e(2).\u003c/li\u003e\n\u003cli\u003eVerna, E.C., et al., \u003cem\u003eLiver transplantation for hepatocellular carcinoma: Management after the transplant.\u003c/em\u003e Am J Transplant, 2020. \u003cstrong\u003e20\u003c/strong\u003e(2): p. 333-347.\u003c/li\u003e\n\u003cli\u003eBerardi, G., et al., \u003cem\u003eTransarterial Radioembolization Can Downstage Intermediate and Advanced Hepatocellular Carcinoma to Liver Transplantation.\u003c/em\u003e Transplantation, 2025. \u003cstrong\u003e109\u003c/strong\u003e(1): p. e54-e63.\u003c/li\u003e\n\u003cli\u003eHwang, S.Y., et al., \u003cem\u003eMultidisciplinary approaches to downstaging hepatocellular carcinoma: present and future.\u003c/em\u003e J Liver Cancer, 2024. \u003cstrong\u003e24\u003c/strong\u003e(2): p. 171-177.\u003c/li\u003e\n\u003cli\u003eHilgard, P., et al., \u003cem\u003eRadioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival.\u003c/em\u003e Hepatology, 2010. \u003cstrong\u003e52\u003c/strong\u003e(5): p. 1741-9.\u003c/li\u003e\n\u003cli\u003eMazzaferro, V., et al., \u003cem\u003eYttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.\u003c/em\u003e Hepatology, 2013. \u003cstrong\u003e57\u003c/strong\u003e(5): p. 1826-37.\u003c/li\u003e\n\u003cli\u003eLee, H.M., et al., \u003cem\u003eLong-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.\u003c/em\u003e J Gastrointest Oncol, 2023. \u003cstrong\u003e14\u003c/strong\u003e(3): p. 1378-1391.\u003c/li\u003e\n\u003cli\u003eAntkowiak, M., et al., \u003cem\u003ePrognostic Role of Albumin, Bilirubin, and ALBI Scores: Analysis of 1000 Patients with Hepatocellular Carcinoma Undergoing Radioembolization.\u003c/em\u003e Cancers (Basel), 2019. \u003cstrong\u003e11\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003eEvirgen, S., et al., \u003cem\u003eIs the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score\u0026apos;s prediction factor for survival?\u003c/em\u003e Hepatol Forum, 2023. \u003cstrong\u003e4\u003c/strong\u003e(3): p. 103-107.\u003c/li\u003e\n\u003cli\u003eMohammadi, H., et al., \u003cem\u003eUsing the Albumin-Bilirubin (ALBI) grade as a prognostic marker for radioembolization of hepatocellular carcinoma.\u003c/em\u003e J Gastrointest Oncol, 2018. \u003cstrong\u003e9\u003c/strong\u003e(5): p. 840-846.\u003c/li\u003e\n\u003cli\u003eWang, Y.Y., et al., \u003cem\u003eAlbumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma.\u003c/em\u003e Br J Surg, 2016. \u003cstrong\u003e103\u003c/strong\u003e(6): p. 725-734.\u003c/li\u003e\n\u003cli\u003eHickey, R., et al., \u003cem\u003eIndependent Analysis of Albumin-Bilirubin Grade in a 765-Patient Cohort Treated with Transarterial Locoregional Therapy for Hepatocellular Carcinoma.\u003c/em\u003e J Vasc Interv Radiol, 2016. \u003cstrong\u003e27\u003c/strong\u003e(6): p. 795-802.\u003c/li\u003e\n\u003cli\u003eFinessi, M., et al., \u003cem\u003eAlbi score predicts overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with selective internal radiation therapy (SIRT).\u003c/em\u003e Radiol Med, 2025. \u003cstrong\u003e130\u003c/strong\u003e(2): p. 271-279.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Liver, hepatocellular carcinoma, trans-arterial radioembolization, ascites, ALBI score","lastPublishedDoi":"10.21203/rs.3.rs-7853339/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7853339/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study evaluates baseline characteristics associated with worsening ascites following TARE. A secondary objective was to examine survival among patients who developed ascites after TARE.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 288 TARE deliveries (237 patients) for primary liver tumors were retrospectively reviewed. Imaging before and six months after TARE was assessed for ascites. Tumor volume, treated area, delivered activity, and liver function tests were reviewed. Logistic regression was performed for risk factors of liver decompensation including pre-existing ascites as a risk factor. Survival curves were plotted for overall survival.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMean (SD) age was 66 (11). 204 were male (71%). 266 (92%), 11 (4%), and 11 (4%) had hepatocellular carcinoma, intrahepatic cholangiocarcinoma and biphenotypic tumor, respectively. 60 (of 288, 21%) patients had pre-existing ascites. New/worsening ascites occurred in 121 (of 288, 42%) [93 (77%) new, 28 (23%) worsening]. Patients with new/worsening ascites had significantly greater increases in bilirubin (p\u0026thinsp;=\u0026thinsp;0.01, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Pre-existing ascites was not associated with increased risk of post-TARE ascites progression, but a higher ALBI score was (OR\u0026thinsp;=\u0026thinsp;2.89, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Neither perfused volume nor activity delivered predicted new/worsening ascites. Child-Pugh class (HR\u0026thinsp;=\u0026thinsp;2.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pre-existing ascites (HR\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), ALBI score (HR\u0026thinsp;=\u0026thinsp;1.5, p\u0026thinsp;\u0026lt;\u0026thinsp;0.011) and new/worsening ascites (HR\u0026thinsp;=\u0026thinsp;2.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were associated with lower survival.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePre-existing ascites is associated with worse survival but should not preclude TARE. ALBI scoring can help distinguish patients at higher risk of post-TARE ascites.\u003c/p\u003e","manuscriptTitle":"Radioembolization of Primary Liver Tumors for Patients with Pre-Existing Ascites: Beyond Child-Pugh score","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 07:30:48","doi":"10.21203/rs.3.rs-7853339/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-11T02:35:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-08T20:05:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"44888918117696500809193735401078265053","date":"2025-10-24T03:47:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-18T01:50:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321560518213310392100839653884328888588","date":"2025-10-15T05:39:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-15T05:26:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-14T12:16:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-14T12:14:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Abdominal Radiology","date":"2025-10-14T02:39:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"05e8ac1d-c483-42c7-b424-1248bb3e88bb","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:11:25+00:00","versionOfRecord":{"articleIdentity":"rs-7853339","link":"https://doi.org/10.1007/s00261-025-05336-6","journal":{"identity":"abdominal-radiology","isVorOnly":false,"title":"Abdominal Radiology"},"publishedOn":"2025-12-11 15:58:38","publishedOnDateReadable":"December 11th, 2025"},"versionCreatedAt":"2025-10-29 07:30:48","video":"","vorDoi":"10.1007/s00261-025-05336-6","vorDoiUrl":"https://doi.org/10.1007/s00261-025-05336-6","workflowStages":[]},"version":"v1","identity":"rs-7853339","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7853339","identity":"rs-7853339","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}