Construction of a prognostic nomogram for transarterial chemoembolization combined with 125I seed implantation for hepatocellular carcinoma with portal vein tumor thrombus: a multicenter retrospective study

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This study constructed and validated a prognostic nomogram using Child-Pugh score, tumor burden, PVTT type, and platelet count to predict survival for hepatocellular carcinoma patients with portal vein tumor thrombus treated with TACE and 125I seed implantation.

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This multicenter retrospective study evaluated 97 patients with hepatocellular carcinoma and first-branch portal vein tumor thrombus who received transarterial chemoembolization combined with 125I seed implantation, with median overall survival (mOS) as the primary outcome. Using univariate screening followed by optimal subset regression and LASSO, the authors built a multivariate Cox model and prognostic nomogram incorporating Child-Pugh score, tumor burden, PVTT type, and platelet (PLT) level, reporting good discrimination and calibration (C-index 0.771 in the primary cohort and 0.744 in external verification) and clinical usefulness on decision-curve analysis. They additionally reported that the combined approach showed better long-term outcomes for patients with type II PVTT, but the paper is a retrospective preprint and does not include any peer-reviewed validation beyond internal/external dataset testing. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Background: To investigate the efficacy of transhepatic arterial chemoembolization (TACE) combined with 125I seed implantation in patients with first-branch portal vein tumor thrombus (PVTT) hepatocellular carcinoma (HCC), establish a prognostic nomogram to determine the prognosis for individual patients. Methods: We retrospectively collected 97 cases of TACE combined with 125I seed implantation in our hospital as the primary cohort. The main observation index of the results of the study was the median overall survival (mOS). Univariate analysis, optimal subset regression(OSR) and LASSO regression were used to screen the variables. The selected variables were included in the multivariate Cox survival regression model, and a prognostic nomogram was developed. The performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. The internal and external verifications were evaluated. Results: The mOS of all patients was 12.5 months. The final determination was made using the Child-Pugh score, tumor burden, PVTT types and PLT level to establish a nomogram prediction model [C -index :0.771 (95% CI: 0.722-0.820)]. The model demonstrated good discrimination and calibration. Application of the nomogram to the external verification data still yielded good discrimination [C-index: 0.744], and good calibration. The decision curve analysis demonstrated that the clinical validity of the model is clinically useful. Conclusion: TACE combined with 125I seed implantation indicated better long-term outcomes in patients with HCC combined with type II PVTT. This nomogram can be used to predict the prognostic survival time of such patients and help doctors make decisions in clinical practice.
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Construction of a prognostic nomogram for transarterial chemoembolization combined with 125I seed implantation for hepatocellular carcinoma with portal vein tumor thrombus: a multicenter retrospective study | 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 Construction of a prognostic nomogram for transarterial chemoembolization combined with 125 I seed implantation for hepatocellular carcinoma with portal vein tumor thrombus: a multicenter retrospective study Xiao-Hui Zhao, Lei Zhao, Yan Zhao, Hai-Liang Li, Zhen Li, Guang-Shao Cao, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1355598/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Background: To investigate the efficacy of transhepatic arterial chemoembolization (TACE) combined with 125I seed implantation in patients with first-branch portal vein tumor thrombus (PVTT) hepatocellular carcinoma (HCC), establish a prognostic nomogram to determine the prognosis for individual patients. Methods: We retrospectively collected 97 cases of TACE combined with 125I seed implantation in our hospital as the primary cohort. The main observation index of the results of the study was the median overall survival (mOS). Univariate analysis, optimal subset regression(OSR) and LASSO regression were used to screen the variables. The selected variables were included in the multivariate Cox survival regression model, and a prognostic nomogram was developed. The performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. The internal and external verifications were evaluated. Results: The mOS of all patients was 12.5 months. The final determination was made using the Child-Pugh score, tumor burden, PVTT types and PLT level to establish a nomogram prediction model [C -index :0.771 (95% CI: 0.722-0.820)]. The model demonstrated good discrimination and calibration. Application of the nomogram to the external verification data still yielded good discrimination [C-index: 0.744], and good calibration. The decision curve analysis demonstrated that the clinical validity of the model is clinically useful. Conclusion: TACE combined with 125I seed implantation indicated better long-term outcomes in patients with HCC combined with type II PVTT. This nomogram can be used to predict the prognostic survival time of such patients and help doctors make decisions in clinical practice. hepatocellular carcinoma portal vein tumor thrombus 125I seed TACE prognostic factors Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1 Introduction Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive tract. It is highly malignant and has a low survival rate (1-2). Portal vein tumor thrombus (PVTT) is a common vascular metastasis route for HCC, and 60-90% of patients with advanced HCC have PVTT (3). The Barcelona Clinic Liver Cancer (BCLC) system is the most widely adopted HCC management guideline (4). According to this system, HCC with PVTT is categorized as BCLC stage C. Although survival after systemic therapy for HCC has improved in recent years, it is still accompanied by poor prognosis of patients with PVTT. It still has a low median survival of 2.7–4.0 months for those who are untreated (5). According to the BCLC system, transarterial chemoembolization (TACE) is the standard treatment option for advanced HCC. However, PVTT is often accompanied by portal hypertension, intrahepatic metastasis, and liver function deterioration (6-7), making the effect of TACE treatment extremely limited. Other reported treatment methods, including 90 Y radioembolization, stereotactic body radiotherapy, systemic therapy, targeted therapy, and immunotherapy have shown some curative effects; however, there is no consensus on PVTT (8-11). Currently, 125 I is widely used in the treatment of HCC and other malignant tumors (12-13). 125 I seed implantation exhibits strong targeting and high conformability. The radiation dose received by tumors increases significantly, while the radiation dose to normal tissues does not increase. This therapy has the advantages of minimal damage to normal tissue, high quality of life, and a short hospital stay (14). At the same time, 125 I seed implantation for PVTT significantly prolongs the median survival time of PVTT patients (15-17). A prospective study in China also showed that 125 I seed implantation therapy had a greater effect on type II PVTT than TACE combined with sorafenib (TACE-S) (18). Some HCC patients with PVTT can use the 125 I seed implantation method to achieve tumor reduction and obtain better curative effects and survival (19). Despite clinical reports on the efficacy and safety of 125 I seed implantation in the treatment of PVTT, there is no nomogram for predicting the survival of patients with HCC and PVTT after 125 I seed implantation with TACE. Therefore, this study aimed to evaluate the tumor response and prognostic factors of 102 HCC patients with type II PVTT who received 125 I seed implantation. A nomogram was constructed and validated based on the clinical characteristics to predict the prognosis of individual patients. 2 Materials And Methods Patient Information This study retrospectively collected clinical data from HCC patients with type II PVTT who underwent TACE with 125 I seed implantation at the our hospital,and two other hospitals from June 1,2016 to December 31,2019. The inclusion criteria were as follows: (1) 18-80 years old patients; (2) diagnosis of HCC based on the Practice Guidelines Committee, American Association for the Study of Liver Diseases (20). The diagnosis of PVTT is based on pathological diagnostic criteria or if the diagnosis of liver cancer is definite and there are imaging signs of PVTT; (3) Child-Pugh grade of A or B (score ≤ 7); (4) Eastern Cooperative Oncology Group (ECOG) performance status of 0–1; (5) patients who are unsuitable for surgery or are not eligible for resection; (6) no history of chemotherapy, radiotherapy, systemic therapy, targeted therapy, or immunotherapy; (7) no severe comorbidities, such as serious cardiac dysfunction, severe liver malfunction, and renal failure; and (8) no history of severe iodine allergy. Classification of PVTT This study adopted the Cheng's classification (21) and divided the patients into four types depending on the degree of PVTT invasion of the portal vein: I0: microscopic tumor thrombosis; type I: tumor thrombus involving secondary and above secondary portal vein branches; type II: cancer thrombus involving the first-level portal vein branch; type IIa: cancer thrombus involving one lobe and first-level portal vein branch, such as the left or right portal vein; type IIb: tumor thrombus involving the two-lobe first-level portal vein branch, that is, involving the left and right portal vein stem; type III: cancer thrombus involving the main portal vein; and type IV: cancer thrombus involving the mesentery and superior mesenteric vein or inferior vena cava. The imaging characteristics of PVTT include actual space-occupying lesions in the portal vein at each stage, enhancement in the arterial phase, and filling defect in the portal vein. At the same time, multi-phase enhanced computed tomography (CT) or dynamic enhanced Magnetic Resonance Imaging (MRI)is used to diagnose PVTT, where it is manifested as portal vein lumen thickening and intravascular low-density filling defect. Type II PVTT was mainly included in this study. All patients provided written informed consent to receive treatment, and this retrospective study was approved by the ethics committee of each hospital. TACE Procedure After using a 5F RH catheter (Termao, Japan) with guide wire to guide routine angiography, the arterial cannula was super-selected to enter the blood supply branch of the tumor. As per previous reports, according to the liver function of the patient, tumor size, and body surface area, 30-50 mg/m 2 (Haizheng Pharmaceutical Co. Ltd., China) and 5-20 ml of super-liquid lipiodol (Guerbet, France)were used and then slowly passed through the catheter after mixing. Arterial infusion chemotherapy was injected, and gelatin sponge particles (500-700 um in diameter, Hangzhou Alikang Medical Technology Co., Ltd., China) were used to supplement the embolization for those who still had residual blood after embolization with iodized oil emulsion. Attention was given to possible participation during surgery. The artery supplying the tumor was embolized, and the endpoint of the embolization was the stagnation of blood flow in the artery supplying the tumor. If a hepatic artery-portal fistula was found during the operation, gelatin sponge particles of different sizes were selected to embolize the fistula according to the intraoperative angiography situation. If a hepatic artery-portal fistula was still found during the second angiography, a coil was used (China, Cook Medical Trading Co.) for mixed embolization. 125 Iodine seed implantation procedure Within 3-5 days after the first TACE, the patient's blood parameters, liver function, and coagulation indicators were re-examined. If the results demonstrated no contraindications to puncture, the patient was treated immediately with 125 I seed implantation in PVTT. First, a treatment planning system (TPS) (FTT Technology Ltd. Co, Beijing, China) was used to evaluate using the image results of preoperative CT examinations to preoperatively plan and determine the number of particles required, the total dose, the location of implanted particles, and the puncture route. Under CT guidance, following the angle and depth of the puncture needle track designed for the PVTT position, a special puncture needle for seed implantation was used for percutaneous PVTT puncture, and CT examination was performed. After the puncture needle entered the PVTT according to the predetermined route, the preoperative TPS plan was followed, and radioactive 125 I particles (Tianjin Xiehe Medical Technology Co., Ltd., China) were implanted. The particles were distributed with a spacing of 5 mm to ensure that the particles were evenly distributed. The needle was removed after completion, the site was pressed for 3 min to stop the bleeding, and a bandage was applied, thereafter. A CT scan was performed to observe the position and quantity of the particles and to check for pneumothorax, hemorrhage, and exudation around the needle tract and the liver, after the implantation was completed. After seed implantation, TPS was used for evaluation. Seed replacement is required if the radiation dose distribution is poor. Follow-up and evaluation Patients were followed-up every 4-6 weeks after TACE. The follow-up included detailed evaluation of clinical manifestations, laboratory indicators, and imaging examinations. The imaging examination used was abdominal multi-phase enhanced CT or multi-phase dynamic enhanced MRI. The main goals of this study were to determine the survival rate of patients at 6, 12, and 18 months after surgery; the median overall survival (mOS); the prognostic factors that affected the survival of the patients and treatment-related adverse reactions. Statistical analysis Chi-square and Mann–Whitney U tests were used to compare the differences among the three institutions in terms of baseline characteristics. The survival curve was calculated using the Kaplan–Meier method. All statistical tests were two-sided tests, and the P value <0.05 indicated statistical significance. The R program was used (version 4.1.2, Foundation for Statistical Computing, Vienna, Austria) in this program. Univariate Cox regression, optimal subset regression(OSR) and LASSO regression with cross-validation were used to initially select variables, and a multivariate Cox survival regression model was used to establish three predictions models built from the different variables. Determining the best model based on the area under the curve (AUC). Thereafter, a prognostic nomogram was established. The performance of the nomogram was assessed by calculating the concordance index (C-index) with 1000 bootstrap resamples. The value of the c index ranged from 0.5 to 1. The higher the c index, the higher the prediction performance. Decision curve analysis (DCA) was used to evaluate the accuracy of the model and net clinical benefits. The flowchart of the analysis is shown in Figure 1. 3 Results Baseline Characteristics From June 1, 2016 to December 31, 2019, a total of 97 patients were enrolled in our hospital as the training set. Two other hospitals enrolled 56 patients as the validation set. The detailed baseline characteristics, including sex, age, ECOG score, Child-Pugh score, tumor number, maximum tumor diameter, total tumor diameter, tumor burden, type of PVTT, AFP level, and blood test results. There was no statistically significant difference in the baseline characteristics of the patients in the training set and the validation set (Table 1). Survival analysis As of June 30,2021, the mOS was 12.5 months (95%CI:11.78-13.22) in the training set patients (Figure 2), the survival rates at 6, 12, and 18 months were 93.8%, 61.9%, and 24.7%, respectively. Preliminary screening of variables As shown in Figure 3, the univariate Cox regression, SOR and LASSO regression with cross-validation were used as preliminary screening variables. The results showed that the variables for univariate Cox regression screening were Child-Pugh score, tumor burden, PVTT type and PLT level. Variables screened for SOR were ECOG score, total tumor diameter, PVTT type, and ALB level. LASSO regression with cross-validation showed that the screening variables were the tumor burden, PVTT type and PLT level. Build different models and compare them The multivariate Cox survival regression model and stepwise backward regression were used to determine the final model variables with the minimum AIC. These variables were then modelled using a multivariate Cox survival regression. The results showed that the variables from univariate Cox regression screening to be analyzed by multivariate Cox survival regression model were Child Pugh score, tumor burden, PVTT type and PLT level (Model 1). The SOR screening variables were finally analyzed for total tumor diameter and PVTT type (Model 2). The variables selected by LASSO regression with cross-validation did not change after multivariate Cox survival regression model analysis (model 2), including the tumor burden, PVTT type, and PLT level (Model 3). In Figure 4, the AUC value of the median overall survival of Model 1 is greater than that of Model 2 and Model 3, therefore, Model 1 were chosen. Development and validation of an individualized prediction model The independent predictors associated with Model 1 identified by multivariate Cox regression analysis are shown in Table 2. A model that incorporated these independent predictors was developed and presented as a nomogram (Figure 5). The calibration curve for median survival probability showed a moderate level of consistency between the predicted and observed results. For internal validation, the C-index for the prediction nomogram was 0.771 (95% CI: 0.722-0.820) for the training set, which was confirmed to be 0.758 via bootstrapping validation. K-fold cross-validation is used for external validation.In the K-fold CV procedure , the training set and validation set is randomly and evenly split into K parts. Model 1 is built based on K − 1 parts of the training set. Prediction accuracy of this candidate model is then evaluated on K − 1 parts of the validation set. By respectively using each of the K parts as the training set and repeating the model building and evaluation procedure, we choose the model with the smallest cross-validation score (the mean squared prediction error MSPE) as the ‘optimal’ model. Our data was run 1000 times, K is equal to 5. At last, the ultimate model is obtained with its parameter estimates as the average values across K candidate ‘optimal’ models. At the same time we get the average of 1000 c-indexes (0.744) (Figure 6). Clinical usefulness The DCA results for the nomogram are shown in Figure 6. The decision curve demonstrated that if the threshold probability of a patient or physician was 25%, using the developed nomogram to predict median survival was more beneficial than using treat-all-patients or treat-none schemes. Adverse reactions related to TACE and 125 I seed implantation Most patients experienced mild adverse reactions related to TACE, including abdominal pain, nausea, and vomiting. After 3-7 days of symptomatic treatment, the patient's symptoms were relieved. No serious adverse reactions related to TACE was observed. Among them, two patients with large intrathoracic gas were treated with closed thoracic drainage. None of the patients experienced any adverse reactions related to surgery. 4 Discussion Analysis of the curative effect of TACE combined with 125 I seed implantation Previous studies have shown that the prognosis of patients with advanced HCC with PVTT is generally poor, and PVTT is a risk factor that affects the survival of patients with HCC (23-25). In this study, TACE combined with 125 I seed implantation was used to treat HCC patients with type II PVTT, and the mOS reached 12.5 months, which is similar to previous reports (15-18). It has been reported that surgical resection may be a treatment for HCC with PVTT (26-28). However, most patients already lose the opportunity to undergo surgical resection by the time the tumor is discovered. Although TACE alone has a certain effect on patients with HCC and PVTT, its effect is often unsatisfactory, with a median survival time of only 7.1 months (29). Owing to obstruction of the portal vein caused by PVTT, reperforming TACE greatly reduces the blood supply to the liver, leading to liver tissue necrosis and liver function failure. Therefore, it is particularly important to control PVTT progression and reduce the occurrence of complete portal vein obstruction. In our study, 125 I seed implantation largely controlled the progress of PVTT, with an ORR of 65%. When PVTT is well controlled, the patient's liver function can be restored to a certain extent. At the same time, a prospective study reported that TACE combined with 125 I seed implantation has a certain effect on maintaining liver function (18). Therefore, for HCC patients with PVTT, it is particularly important to actively control PVTT. Radiotherapy is also an important local treatment for PVTT (8). 125 I seed implantation is as effective as Stereotactic Body Radiation Therapy (SBRT) and Three Dimensional Conformal Radiation Therapy (3DCR) as IR therapy. A randomized, open-label clinical trial to compare the efficacy and safety of TACE combined with radiotherapy and sorafenib in the treatment of liver cancer and large vessel invasion (30) showed that, compared with sorafenib, the former can prolong progression-free survival and overall survival of patients, with an mOS of 13.1 months. The PVTT classification is closely related to the prognosis and therapeutic effects of HCC. In our study, we conducted a subgroup analysis of type IIa and type IIb PVTT and compared the difference in survival. The results showed that the mOS of patients with type IIa PVTT was significantly higher than those with type IIb PVTT. This may be because when only one branch of the portal vein is blocked by a tumor thrombus, the liver function is better, and the portal vein pressure is maintained relatively low compared to when both branches of the portal vein are blocked. Patients with type IIa PVTT have better liver function and lower portal pressure than patients with type IIb PVTT; therefore, they can withstand more treatment. Previous studies have shown that type III PVTT is an independent predictor of poor prognosis in such patients. The higher the degree of PVTT (31-33), the worse the treatment effect, which is similar to the results of the present study. Analysis and clinical significance of predictive models In this study, the results showed that Child-Pugh score, tumor burden, PVTT and PLT level were significant risk factors for OS. The prognostic factors of HCC have been shown to include maximum tumor diameter, tumor type, tumor stage, cirrhosis, Child-Pugh score, AFP level, and serological indicators of liver function (34-36), which are similar to the results of our study. The “Six and Twelve” model proposed in the previous study is an excellent model for HCC treatment with TACE (37). This model indicates that patients with cumulative tumor size > 12 cm have a poor prognosis, and the mOS is only 15.8 months. This study also used the sum of tumor size (cm) and tumor number to evaluate the tumor burden. According to the characteristics of the enrolled patients, the standard deviation of the patient’s tumor burden was 7.71, indicating that the tumor burden was relatively large. However, it is worth noting that the "Six and Twelve" model does not evaluate vascular metastasis, and the appearance of PVTT undoubtedly increases the tumor burden and patient survival also deteriorate. The models established by the variables screened by different methods are not the same; however, the best model can be selected only on the basis of rigorous statistics based on previous research and practical clinical significance. This shows that even in patients with portal vein metastasis, the use of the sum of maximum tumor diameter and number to evaluate intrahepatic lesions, combined with the treatment of PVTT, can be used for HCC patients with type II PVTT who undergo TACE combined with 125 I seed implantation therapy. According to the prediction model of this study, it is feasible to predict the prognosis of such patients. A unique feature of this study was the development of a personalized predictive model to predict the prognosis of each patient. From the perspective of tumor burden, we constructed a nomogram to predict the mOS and combined the Child-Pugh score and PLT level to predict the prognosis of type II PVTT from more perspectives. Previous studies and discussions have also illustrated the impact of the Child-Pugh score on HCC patients with type II PVTT. Simultaneously, we evaluated the model from different angles, conducted external verifications, and obtained good results. In statistical analysis, the general model usually directly brings the validation set input into the training set model to obtain the c-index. This study uses the K-fold CV procedure, and uses cross-validation to achieve multiple c-index calculations. The verification results are more robust than traditional methods (39). Research based on TNM staging only focuses on the change in the size of the patient’s tumor and whether it has metastasized (38) while ignoring the impact of clinical indicators and the overall patient survival. It is undoubtedly one-sided to consider the survival of patients solely based on tumor status, and the development of the nomogram provides a more comprehensive basis for judgment. At present, the nomogram has been shown to have a certain role in evaluating the prognosis of many cancer patients, including those with HCC and PVTT (40-42). It reflects the characteristics of the tumor and the patient's state, including additional clinical parameters. Therefore, the nomogram is considered more advantageous than the traditional staging method. Some researchers have proposed it as an alternative method or a new standard for guiding cancer treatment (43). Security and limitations In terms of safety, TACE combined with 125 I seed implantation for PVTT is well tolerated, consistent with the results of other studies (15-18). This study has certain limitations. First, it is a retrospective study with a small sample size, which may have led to selection bias. The results need to be further confirmed in prospective, multicenter, randomized controlled trials. Although the Child-Pugh score, tumor burden, and PVTT type were included in the nomogram as predictors, they showed a good predictive ability. Owing to the small number of indicators included in this study, more effective indicators may not be included. Therefore, the prediction efficiency of the model must be further improved. In conclusion, there are still controversies about the treatment of PVTT, but most of the current research and clinical practice showed that for HCC patients with PVTT, combined treatment should be used to obtain better treatment results. This study showed that TACE combined with 125 I seed implantation is an effective method for the treatment of HCC with PVTT. Based on the "Six and Twelve" model, combined with the Child-Pugh score and PVTT type, it is a predictive model that can be used to predict mOS in patients with HCC and PVTT receiving treatment. References Massarweh NN, El-Serag HB. Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control. 2017 Jul-Sep;24(3):1073274817729245. doi: 10.1177/1073274817729245. PMID: 28975830; PMCID: PMC5937247. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. 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Radiofrequency ablation combined with transarterial chemoembolization in treatment of hepatocellular carcinoma adjacent to the second hepatic hilus. Abdom Radiol (NY). 2021 Oct 11. doi: 10.1007/s00261-021-03304-4. Epub ahead of print. PMID: 34635940. Bruix J, Sherman M. Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005, 42(5):1208-1236. doi: 10.1002/hep.20933. Zhang XP, Gao YZ, Chen ZH, et al. An Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus Scoring System as an Aid to Decision Making on Hepatectomy for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: A Multicenter Study. Hepatology, 2019. 69(5): p. 2076-2090. doi: 10.1002/hep.30490. Zhou TY, Chen SQ, Wang HL, et, al. Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study. J Cancer. 2021;12(15):4522-4529. doi: 10.7150/jca.54650. Luo F, Li M, Ding J, Zheng S. The Progress in the Treatment of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus. Front Oncol. 2021 Sep 23;11:635731. doi: 10.3389/fonc.2021.635731. PMID: 34631513; PMCID: PMC8496502. Yang M, Fang Z, Yan Z, et al. Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial. J Cancer Res Clin Oncol. 2014; 140(2):211-219. doi: 10.1007/s00432-013-1568-0. Poon R T, Fan S T, Ng I O, et al. Prognosis after hepatic resection for stage IVA hepatocellular carcinoma: a need for reclassification[J]. Ann Surg, 2003,237(3):376-383. Kamiyama T, Nakanishi K, Yokoo H, et al. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma[J]. Int J Clin Oncol, 2007,12(5):363-368. Zheng N, Wei X, Zhang D, et al. Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus. Medicine (Baltimore). 2016 Jun;95(26):e3959. doi: 10.1097/MD.0000000000003959. PMID: 27367992; PMCID: PMC4937906. Allaire M, Goumard C, Lim C, et al. New frontiers in liver resection for hepatocellular carcinoma. JHEP Rep. 2020 Jun 4;2(4):100134. doi: 10.1016/j.jhepr.2020.100134. PMID: 32695968; PMCID: PMC7360891. Song DS, Bae SH, Song MJ, et al. Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol. 2013,19(29):4679-4688. doi: 10.3748/wjg.v19.i29.4679. Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol.2018,4(5):661-669. doi: 10.1016/j.radonc.2017.11.013. Yang M, Fang Z, Yan Z, et al. Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial[J]. J Cancer Res Clin Oncol, 2014,140(2):211-219. Huang M, Lin Q, Wang H, et al. Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study[J]. Eur Radiol, 2016,26(10):3428-3436. Sun H, Zhang M, Liu R, et al. Endovascular implantation of 125I seed combined with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma. Future Oncol. 2018 May;14(12):1165-1176. doi: 10.2217/fon-2017-0354. Epub 2018 Jan 16. PMID: 29334777. Cerban R, Ester C, Iacob S, et al. Predictive Factors of Tumor Recurrence and Survival in Patients with Hepatocellular Carcinoma treated with Transarterial Chemoembolization. J Gastrointestin Liver Dis. 2018 Dec;27(4):409-417. doi: 10.15403/jgld.2014.1121.274.fcr. PMID: 30574623. Jeong SO, Kim EB, Jeong SW, et al. Predictive Factors for Complete Response and Recurrence after Transarterial Chemoembolization in Hepatocellular Carcinoma. Gut Liver. 2017 May 15;11(3):409-416. doi: 10.5009/gnl16001. PMID: 28208001; PMCID: PMC5417784. Hu HT, Kim JH, Lee LS, et al. Chemoembolization for hepatocellular carcinoma: multivariate analysis of predicting factors for tumor response and survival in a 362-patient cohort. J Vasc Interv Radiol. 2011 Jul;22(7):917-23. doi: 10.1016/j.jvir.2011.03.005. Epub 2011 May 14. PMID: 21571545. Wang Q, Xia D, Bai W, et al. Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study. J Hepatol. 2019 May;70(5):893-903. doi: 10.1016/j.jhep.2019.01.013. Epub 2019 Jan 18. PMID: 30660709. Satala CB, Jung I, Kobori L, et al. Benefits of the 8th American Joint Committee on Cancer System for Hepatocellular Carcinoma Staging. J Gastrointest Cancer. 2021 Mar;52(1):243-248. doi: 10.1007/s12029-020-00394-z. PMID:32173767. Jung Y, Hu J. A K-fold Averaging Cross-validation Procedure. J Nonparametr Stat. 2015;27(2):167-179. doi: 10.1080/10485252.2015.1010532. Epub 2015 Feb 26. PMID: 27630515; PMCID: PMC5019184. Huang YQ, Liang CH, He L, et al. Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer. J Clin Oncol. 2016 Jun 20;34(18):2157-64. doi: 10.1200/JCO.2015.65.9128. Epub 2016 May 2. Erratum in: J Clin Oncol. 2016 Jul 10;34(20):2436. PMID: 27138577. Li X, Ye Z, Lin S, Pang H. Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram. BMC Cancer. 2021 Jun 15;21(1):701. doi: 10.1186/s12885-021-08469-1. PMID: 34126955; PMCID: PMC8204556. Zhang L, Sun JH, Hou ZH, et al. Prognosis Nomogram for Hepatocellular Carcinoma Patients with Portal Vein Invasion Undergoing Transarterial Chemoembolization Plus Sorafenib Treatment: A Retrospective Multicentre Study. Cardiovasc Intervent Radiol. 2021 Jan;44(1):63-72. doi: 10.1007/s00270-020-02579-2. Epub 2020 Sep 23. PMID: 32965582. Iasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008 Mar 10;26(8):1364-70. doi: 10.1200/JCO.2007.12.9791. PMID: 18323559. Tables Table 1. Baseline characteristics of patients with type IIa and IIb PVTT in the primary cohort Variable level Training set Validation set P-value N 97 56 Sex Male 85 (87.6) 49 (87.5) 1.000 Female 12 (12.4) 7 (12.5) Age 57.21 ± 10.99 58.96 ± 9.76 0.323 ECOG 0 39 (40.2) 27 (48.2) 0.427 1 58 (59.8) 29 (51.8) ChildPugh 5 40 (41.2) 25 (44.6) 0.915 6 30 (30.9) 16 (28.6) 7 27 (27.8) 15 (26.8) Number 1 45 (46.4) 22 (39.3) 0.317 2-4 40 (41.2) 22 (39.3) ≥5 12 (12.4) 12 (21.4) Maximum tumor diameter < 60 mm 60 (61.9) 36 (64.3) 0.900 ≥60 mm 37 (38.1) 20 (35.7) Total tumor diameter < 100mm 69 (71.1) 45 (80.4) 0.285 ≥100 mm 28 (28.9) 11 (19.6) Tumor burden 7.71 (3.09) 8.29 (2.26) 0.226 Position Right/Left 50 (51.5) 22 (39.3) 0.195 Biloba 47 (48.5) 34 (60.7) PVTT IIa 56 (57.7) 35 (62.5) 0.683 IIb 41 (42.3) 21 (37.5) Preoperative AFP < 400 ng/mL 58 (59.8) 35 (62.5) 0.874 ≥400 ng/mL 39 (40.2) 21 (37.5) PLT (×109/L) 146.97 ± 39.86 145.79 ± 34.97 0.854 PT (s) 13.12 ± 1.56 13.19 ± 1.36 0.779 TBL (umol/L) 23.69 ± 15.96 20.33 ± 13.27 0.186 ALB (g/L) 38.52 ± 5.96 37.99 ± 4.37 0.564 WBC (×10 9 /L) 5.31 ± 2.25 5.37 ± 1.72 0.876 RBC (×10 9 /L) 4.32 ± 0.61 4.45 ± 0.55 0.201 HGB (g/L) 132.34 ± 18.79 130.12 ± 14.38 0.447 Unless otherwise indicated, data are presented as numbers of patients. Data are presented as mean (standard deviation) Abbreviations: ECOG=Eastern Cooperative Oncology Group; PVTT= portal vein tumor thrombosis; AFP = alpha fetoprotein; PLT=platelet; PT= prothrombin time; TBL= total bilirubin; ALB= albumin; WBC = white blood cell; RBC = red blood cell; HGB = hemoglobin; Table 2. Risk Factors Affecting Survival in Model 1 Intercept and Variable β Model 1 P Odds Ratio 95% CI Child-Pugh Score-6:5 0.56 1.675 0.994-2.824 0.052 Child-Pugh Score-7:5 0.598 1.819 1.071-3.088 0.027 PVTT types 1.356 3.881 2.340-6.434 0.000 Tumor burden 0.248 1.281 0.476-1.010 0.000 PLT -0.006 0.994 0.473-0.992 0.045 C-index Primary cohort 0.771 (0.722-0.820) Validation cohort 0.744 NOTE. b is the regression coefficient. Declarations Funding : Grant Support: Technology Major Project of the Ministry of Science and Technology of China (2018ZX10303502). Henan Province Medical Science and Technology Research Project (201701032). Medical Education Research Project of Henan Province (Wjlx2021334). Henan Province Natural Science Foundation (212300410403) .Science and Technology Department of Henan Province (No. 212102310162); Medical Science and Technology Research Project of Henan Province (No. LHGJ20190633).Henan Province Natural Science Foundation (222300420574). Competing Interests : The authors have no relevant financial or non-financial interests to disclose. Author Contributions : Conception and design: HTH Patient selection and treatment: XHZ, HLL, LZ, GSC, Data collection, analysis and interpretation: XHZ, YZ, SJX, HLL Data interpretation: HTH, XHZ, YZ, SXJ, HLL Undertook steering committee activities and critical statistical processing: HTH, YZ Manuscript writing:XHZ, YZ Manuscript reviewing: HTH Ethics approval : The study protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki, and was approved by the Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University review board. Data Availability : The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Consent to participate : All of the patients sign in the informed consent form. Consent for publication : None. Additional Declarations No competing interests reported. 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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-1355598","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":110461607,"identity":"c5fe1ce6-12a9-43b2-87e0-3cbdc243e3f4","order_by":0,"name":"Xiao-Hui Zhao","email":"","orcid":"","institution":"The Affiliated Cancer Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiao-Hui","middleName":"","lastName":"Zhao","suffix":""},{"id":110461608,"identity":"17d21dfd-1891-41ae-898d-363989618eed","order_by":1,"name":"Lei Zhao","email":"","orcid":"","institution":"Henan Red Cross Blood 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14:44:05","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.3.rs-1355598/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-1355598/v3","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22188804,"identity":"7cd4701b-6222-4906-96e7-5e3e862b339c","added_by":"auto","created_at":"2022-06-02 15:26:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20349,"visible":true,"origin":"","legend":"\u003cp\u003eStatistical analysis flow chart.\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/ec72bd0766ea6bcddc3f1f60.png"},{"id":22188369,"identity":"95050da8-f82d-4d59-8d9b-27497c781f0d","added_by":"auto","created_at":"2022-06-02 15:16:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":97197,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier\u0026nbsp;curve of the overall survival in the training set.\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/858f68a4434e40b02608157b.png"},{"id":22188372,"identity":"0fbcc10f-1e60-4d3d-bda9-c4b0639a9cc8","added_by":"auto","created_at":"2022-06-02 15:16:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132005,"visible":true,"origin":"","legend":"\u003cp\u003eLASSO introduces a variable λ (lambda, tuning coefficient or penalty value), as shown in Figure 3a: as λ increases, the regression coefficient β of each variable decreases, and two penalty values λ are given in Figure 3b: one is The λ value when the MSE (Mean Squared Error) is the smallest; the other is the λ value of the simplest model obtained within a variance range of the lambda.min value, ie lambda.1se, which is generally chosen (three variables). OSR: As observed in Figure 3c, the abscissa is the independent variable, the ordinate is the adjustment R2, and the adjustment R2 of the regression equation built by the top variable is the largest (three variables).The univariate Cox regression\u0026nbsp;results are shown in Fig. 4d.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/60bed448744173ff9623aa4c.png"},{"id":22188653,"identity":"98127cb7-54f8-4d42-aeeb-f713dacbd57b","added_by":"auto","created_at":"2022-06-02 15:21:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":107943,"visible":true,"origin":"","legend":"\u003cp\u003eThe AUC values of Model 1, Model 2, and Model 3 are shown in the figure, with Model 1 having the largest value.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/d59f565eb4062ba64bfe663e.png"},{"id":22188655,"identity":"309a0b03-1520-41bd-8695-567bcf3ab8d6","added_by":"auto","created_at":"2022-06-02 15:21:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":350231,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram established for median survival prediction based on Model 1. Nomogram calibration curves.\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/227e8c766179afccec179f44.png"},{"id":22188376,"identity":"6f070c53-9277-46f2-99c4-1c4b0f766a28","added_by":"auto","created_at":"2022-06-02 15:16:08","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":438422,"visible":true,"origin":"","legend":"\u003cp\u003eAfter 5-fold 1000 Cross-validation Procedures, the box plot of the C-index is shown in Figure 6a.\u0026nbsp;Decision curve analysis for the nomogram based on clinical characteristics\u0026nbsp;(Fig. 6a). The broken line represents the nomogram. The thick line represents all negative samples. The participants received no interventions. The fine line represents all positive samples, and these participants received interventions.\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/7e26e552f201a90389f6761d.png"},{"id":22201279,"identity":"9fd201f3-0d11-4e2b-8881-25b2c28be000","added_by":"auto","created_at":"2022-06-02 21:01:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1167460,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1355598/v3/c2aa165d-a05f-4d33-bdb2-23936a78847c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eConstruction of a prognostic nomogram for transarterial chemoembolization combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation for hepatocellular carcinoma with portal vein tumor thrombus: a multicenter retrospective study\u003c/p\u003e","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) is one of the most common malignant\u0026nbsp;tumors\u0026nbsp;of the digestive tract. It is\u0026nbsp;highly malignant and\u0026nbsp;has\u0026nbsp;a low survival rate\u0026nbsp;(1-2).\u0026nbsp;Portal vein\u0026nbsp;tumor\u0026nbsp;thrombus (PVTT) is a common vascular metastasis route for HCC, and 60-90% of patients with advanced HCC\u0026nbsp;have\u0026nbsp;PVTT\u0026nbsp;(3).\u0026nbsp;The Barcelona\u0026nbsp;Clinic Liver Cancer\u0026nbsp;(BCLC) system is the most widely adopted HCC management guideline\u0026nbsp;(4).\u0026nbsp;According to this system, HCC with PVTT is categorized as BCLC stage\u0026nbsp;C. Although survival after systemic therapy\u0026nbsp;for\u0026nbsp;HCC has improved in recent years, it is\u0026nbsp;still\u0026nbsp;accompanied by\u0026nbsp;poor\u0026nbsp;prognosis\u0026nbsp;of\u0026nbsp;patients with PVTT. It\u0026nbsp;still has a low median survival of 2.7\u0026ndash;4.0 months\u0026nbsp;for those\u0026nbsp;who\u0026nbsp;are\u0026nbsp;untreated\u0026nbsp;(5).\u0026nbsp;According to the BCLC system, transarterial chemoembolization (TACE) is the standard treatment option for advanced HCC. However,\u0026nbsp;PVTT is often accompanied by portal hypertension, intrahepatic metastasis,\u0026nbsp;and liver function deterioration\u0026nbsp;(6-7),\u0026nbsp;making\u0026nbsp;the effect of\u0026nbsp;TACE treatment extremely limited. Other reported treatment methods, including \u003csup\u003e90\u003c/sup\u003eY radioembolization, stereotactic body radiotherapy, systemic therapy, targeted therapy, and immunotherapy have shown some curative effects; however, there is no consensus on PVTT\u0026nbsp;(8-11).\u003c/p\u003e\n\u003cp\u003eCurrently, \u003csup\u003e125\u003c/sup\u003eI\u0026nbsp;is\u0026nbsp;widely used in the treatment of HCC and other malignant\u0026nbsp;tumors\u0026nbsp;(12-13).\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation\u0026nbsp;exhibits\u0026nbsp;strong targeting and high conformability. The radiation dose received by\u0026nbsp;tumors\u0026nbsp;increases significantly, while the radiation dose\u0026nbsp;to\u0026nbsp;normal tissues\u0026nbsp;does\u0026nbsp;not\u0026nbsp;increase. This therapy has the advantages of\u0026nbsp;minimal damage to\u0026nbsp;normal tissue, high quality of life,\u0026nbsp;and\u0026nbsp;a\u0026nbsp;short hospital stay\u0026nbsp;(14).\u0026nbsp;At the same time, \u003csup\u003e125\u003c/sup\u003eI seed implantation for PVTT significantly prolongs the median survival time of PVTT patients\u0026nbsp;(15-17).\u0026nbsp;A prospective study in China also\u0026nbsp;showed\u0026nbsp;that \u003csup\u003e125\u003c/sup\u003eI seed implantation therapy\u0026nbsp;had\u0026nbsp;a greater effect on type II PVTT\u0026nbsp;than TACE\u0026nbsp;combined with sorafenib\u0026nbsp;(TACE-S)\u0026nbsp;(18).\u0026nbsp;Some HCC patients with PVTT can use\u0026nbsp;the\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation\u0026nbsp;method to achieve tumor reduction\u0026nbsp;and\u0026nbsp;obtain\u0026nbsp;better curative\u0026nbsp;effects\u0026nbsp;and survival\u0026nbsp;(19).\u003c/p\u003e\n\u003cp\u003eDespite clinical reports on the efficacy and safety of\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI\u0026nbsp;seed implantation in the treatment of PVTT, there is no nomogram for predicting\u0026nbsp;the\u0026nbsp;survival of patients with HCC and PVTT after \u003csup\u003e125\u003c/sup\u003eI seed implantation with TACE. Therefore, this study\u0026nbsp;aimed\u0026nbsp;to evaluate the\u0026nbsp;tumor\u0026nbsp;response and prognostic factors of 102 HCC patients with type II PVTT who received\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation. A nomogram was constructed and validated based on the clinical characteristics to predict the prognosis of individual patients.\u003c/p\u003e"},{"header":"2 Materials And Methods","content":"\u003ch2\u003ePatient Information\u003c/h2\u003e\n\u003cp\u003eThis study retrospectively collected clinical data from\u0026nbsp;HCC\u0026nbsp;patients with type II PVTT\u0026nbsp;who underwent\u0026nbsp;TACE with \u003csup\u003e125\u003c/sup\u003eI seed implantation at the\u0026nbsp;our\u0026nbsp;hospital,and two other hospitals\u0026nbsp;from June 1,2016 to\u0026nbsp;December 31,2019.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria\u0026nbsp;were as follows: (1) 18-80 years old patients; (2) diagnosis of HCC based on the Practice Guidelines Committee, American Association for the Study of Liver Diseases\u0026nbsp;(20).\u0026nbsp;The diagnosis of PVTT is based on pathological diagnostic criteria or if the diagnosis of liver cancer is definite and there are imaging signs of PVTT; (3) Child-Pugh grade\u0026nbsp;of\u0026nbsp;A or B\u0026nbsp;(score \u0026le; 7); (4) Eastern Cooperative Oncology Group (ECOG) performance status of 0\u0026ndash;1; (5)\u0026nbsp;patients\u0026nbsp;who are unsuitable for surgery or are not eligible for resection; (6)\u0026nbsp;no\u0026nbsp;history of chemotherapy, radiotherapy, systemic therapy, targeted therapy,\u0026nbsp;or\u0026nbsp;immunotherapy; (7)\u0026nbsp;no severe\u0026nbsp;comorbidities, such as\u0026nbsp;serious cardiac dysfunction, severe liver\u0026nbsp;malfunction,\u0026nbsp;and\u0026nbsp;renal\u0026nbsp;failure;\u0026nbsp;and\u0026nbsp;(8)\u0026nbsp;no history of severe iodine allergy.\u003c/p\u003e\n\u003ch2\u003eClassification of PVTT\u003c/h2\u003e\n\u003cp\u003eThis study adopted\u0026nbsp;the\u0026nbsp;Cheng\u0026apos;s classification\u0026nbsp;(21)\u0026nbsp;and divided\u0026nbsp;the patients\u0026nbsp;into four types depending on the degree of PVTT invasion of the portal vein: I0: microscopic\u0026nbsp;tumor\u0026nbsp;thrombosis; type I:\u0026nbsp;tumor\u0026nbsp;thrombus involving secondary and above secondary portal vein branches; type II:\u0026nbsp;cancer\u0026nbsp;thrombus\u0026nbsp;involving\u0026nbsp;the first-level portal vein branch;\u0026nbsp;type IIa: cancer thrombus\u0026nbsp;involving\u0026nbsp;one lobe and first-level portal vein branch, such as the left or right portal vein;\u0026nbsp;type\u0026nbsp;IIb:\u0026nbsp;tumor\u0026nbsp;thrombus\u0026nbsp;involving\u0026nbsp;the two-lobe first-level portal vein branch, that is, involving the left and right portal vein\u0026nbsp;stem; type\u0026nbsp;III:\u0026nbsp;cancer\u0026nbsp;thrombus involving the main portal vein;\u0026nbsp;and\u0026nbsp;type\u0026nbsp;IV:\u0026nbsp;cancer\u0026nbsp;thrombus involving the mesentery and superior mesenteric vein or inferior vena cava.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The imaging\u0026nbsp;characteristics of PVTT\u0026nbsp;include\u0026nbsp;actual space-occupying lesions in the portal vein at each stage, enhancement in the arterial phase, and filling defect in the portal vein. At the same time, multi-phase enhanced computed tomography (CT) or dynamic enhanced Magnetic Resonance Imaging\u0026nbsp;(MRI)is used to diagnose PVTT, where it is manifested\u0026nbsp;as\u0026nbsp;portal vein lumen thickening and intravascular low-density filling defect. Type II PVTT was mainly included in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent to receive treatment, and\u0026nbsp;this\u0026nbsp;retrospective study was approved by the ethics committee of each hospital.\u003c/p\u003e\n\u003ch2\u003eTACE\u0026nbsp;Procedure\u003c/h2\u003e\n\u003cp\u003eAfter using a 5F RH catheter (Termao, Japan)\u0026nbsp;with\u0026nbsp;guide wire to guide routine angiography, the arterial cannula was super-selected to enter the blood supply branch of the\u0026nbsp;tumor. As per previous reports, according to the liver function of the patient,\u0026nbsp;tumor\u0026nbsp;size,\u0026nbsp;and body surface area,\u0026nbsp;30-50\u0026nbsp;mg/m\u003csup\u003e2\u003c/sup\u003e (Haizheng Pharmaceutical Co. Ltd., China) and 5-20 ml of super-liquid lipiodol (Guerbet, France)were\u0026nbsp;used\u0026nbsp;and then slowly\u0026nbsp;passed\u0026nbsp;through the catheter after mixing. Arterial infusion chemotherapy\u0026nbsp;was\u0026nbsp;injected, and\u0026nbsp;gelatin\u0026nbsp;sponge particles (500-700 um in diameter, Hangzhou Alikang Medical Technology Co., Ltd., China)\u0026nbsp;were\u0026nbsp;used to supplement the embolization for those who still\u0026nbsp;had\u0026nbsp;residual blood after embolization with\u0026nbsp;iodized\u0026nbsp;oil emulsion.\u0026nbsp;Attention was given\u0026nbsp;to possible participation during\u0026nbsp;surgery.\u0026nbsp;The artery supplying the\u0026nbsp;tumor\u0026nbsp;was embolized, and the\u0026nbsp;endpoint\u0026nbsp;of the embolization was the stagnation of blood flow in the artery supplying the\u0026nbsp;tumor. If a hepatic artery-portal fistula was found during the operation,\u0026nbsp;gelatin\u0026nbsp;sponge particles of different sizes\u0026nbsp;were\u0026nbsp;selected to embolize the fistula according to the intraoperative angiography\u0026nbsp;situation. If\u0026nbsp;a\u0026nbsp;hepatic artery-portal fistula was still found during the second angiography, a coil was used (China, Cook Medical Trading Co.) for mixed embolization.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003csup\u003e125\u003c/sup\u003eIodine\u0026nbsp;seed implantation procedure\u003c/h2\u003e\n\u003cp\u003eWithin 3-5 days after the first TACE, the patient\u0026apos;s blood\u0026nbsp;parameters, liver function, and coagulation indicators\u0026nbsp;were\u0026nbsp;re-examined. If the results\u0026nbsp;demonstrated\u0026nbsp;no contraindications to\u0026nbsp;puncture, the patient was treated immediately\u0026nbsp;with\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation in PVTT. First, a treatment planning system (TPS) (FTT Technology Ltd. Co, Beijing, China) was used to evaluate\u0026nbsp;using\u0026nbsp;the image results of preoperative CT examinations to preoperatively plan and determine the number of particles required, the total dose, the location of implanted particles, and the puncture route. Under CT guidance,\u0026nbsp;following\u0026nbsp;the angle and depth of the puncture needle track designed for the PVTT position,\u0026nbsp;a\u0026nbsp;special puncture needle for seed implantation\u0026nbsp;was\u0026nbsp;used for percutaneous PVTT puncture, and CT examination\u0026nbsp;was\u0026nbsp;performed. After the puncture needle\u0026nbsp;entered\u0026nbsp;the PVTT according to the predetermined route, the preoperative TPS plan\u0026nbsp;was followed, and\u0026nbsp;radioactive \u003csup\u003e125\u003c/sup\u003eI particles (Tianjin Xiehe Medical Technology Co., Ltd., China) were implanted. The\u0026nbsp;particles\u0026nbsp;were distributed\u0026nbsp;with\u0026nbsp;a\u0026nbsp;spacing of\u0026nbsp;5\u0026nbsp;mm\u0026nbsp;to\u0026nbsp;ensure that\u0026nbsp;the particles\u0026nbsp;were\u0026nbsp;evenly distributed. The\u0026nbsp;needle\u0026nbsp;was\u0026nbsp;removed\u0026nbsp;after completion, the\u0026nbsp;site was pressed\u0026nbsp;for 3\u0026nbsp;min\u0026nbsp;to stop the bleeding,\u0026nbsp;and\u0026nbsp;a\u0026nbsp;bandage\u0026nbsp;was applied, thereafter. A CT scan\u0026nbsp;was\u0026nbsp;performed to observe the position and quantity of the particles and to check\u0026nbsp;for\u0026nbsp;pneumothorax,\u0026nbsp;hemorrhage,\u0026nbsp;and exudation around\u0026nbsp;the\u0026nbsp;needle tract and the liver, after the implantation\u0026nbsp;was\u0026nbsp;completed. After seed implantation, TPS\u0026nbsp;was\u0026nbsp;used for evaluation.\u0026nbsp;Seed replacement is required\u0026nbsp;if\u0026nbsp;the radiation dose distribution is\u0026nbsp;poor.\u003c/p\u003e\n\u003ch2\u003eFollow-up and evaluation\u003c/h2\u003e\n\u003cp\u003ePatients were\u0026nbsp;followed-up every 4-6 weeks after TACE. The follow-up\u0026nbsp;included\u0026nbsp;detailed evaluation of clinical manifestations, laboratory indicators,\u0026nbsp;and imaging examinations. The imaging examination used was\u0026nbsp;abdominal\u0026nbsp;multi-phase enhanced CT or\u0026nbsp;multi-phase\u0026nbsp;dynamic enhanced MRI. The main goals of this study\u0026nbsp;were to determine\u0026nbsp;the survival rate of patients at 6, 12, and 18 months after surgery;\u0026nbsp;the median overall survival\u0026nbsp;(mOS);\u0026nbsp;the prognostic factors that\u0026nbsp;affected\u0026nbsp;the survival of the patients and treatment-related adverse reactions.\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eChi-square and Mann\u0026ndash;Whitney U tests were used to compare the differences among\u0026nbsp;the\u0026nbsp;three institutions in\u0026nbsp;terms of\u0026nbsp;baseline characteristics. The survival curve was calculated\u0026nbsp;using the\u0026nbsp;Kaplan\u0026ndash;Meier method. All statistical tests were two-sided tests, and the P value\u0026nbsp;\u0026lt;0.05 indicated statistical significance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe R program was used (version 4.1.2, Foundation for Statistical Computing, Vienna, Austria) in this program. Univariate Cox regression, optimal subset regression(OSR) and LASSO regression with cross-validation were used to initially select variables, and a multivariate Cox survival regression model was used to establish three predictions models built from the different variables. Determining the best model based on the area under the curve (AUC). Thereafter, a prognostic nomogram was established. The performance of the nomogram was assessed by calculating the concordance index (C-index) with 1000 bootstrap resamples. The value of the c index ranged from 0.5 to 1. The higher the c index, the higher the prediction performance. Decision curve analysis (DCA) was used to evaluate the accuracy of the model and net clinical benefits. The flowchart of the analysis is shown in Figure 1.\u003c/p\u003e"},{"header":"3 Results","content":"\u003ch2\u003eBaseline Characteristics\u003c/h2\u003e\n\u003cp\u003eFrom June 1, 2016 to December 31, 2019, a total of 97 patients were\u0026nbsp;enrolled in our hospital as the training set. Two other hospitals\u0026nbsp;enrolled 56 patients as the validation set.\u0026nbsp;The\u0026nbsp;detailed\u0026nbsp;baseline characteristics, including sex, age, ECOG score, Child-Pugh score,\u0026nbsp;tumor\u0026nbsp;number, maximum\u0026nbsp;tumor\u0026nbsp;diameter, total tumor diameter,\u0026nbsp;tumor burden, type\u0026nbsp;of PVTT, AFP level, and blood test results. There was no statistically significant difference in the baseline characteristics of the patients in the training set and the validation set (Table 1).\u003c/p\u003e\n\u003ch2\u003eSurvival analysis\u003c/h2\u003e\n\u003cp\u003eAs of June 30,2021, the mOS was 12.5 months\u0026nbsp;(95%CI:11.78-13.22)\u0026nbsp;in the training set patients\u0026nbsp;(Figure 2),\u0026nbsp;the survival rates\u0026nbsp;at\u0026nbsp;6, 12,\u0026nbsp;and 18 months were\u0026nbsp;93.8%,\u0026nbsp;61.9%,\u0026nbsp;and 24.7%,\u0026nbsp;respectively.\u003c/p\u003e\n\u003ch2\u003ePreliminary screening of variables\u003c/h2\u003e\n\u003cp\u003eAs shown\u0026nbsp;in\u0026nbsp;Figure 3,\u0026nbsp;the univariate Cox\u0026nbsp;regression, SOR\u0026nbsp;and LASSO regression\u0026nbsp;with\u0026nbsp;cross-validation\u0026nbsp;were used as preliminary\u0026nbsp;screening variables. The results showed that the variables for\u0026nbsp;univariate Cox\u0026nbsp;regression screening were\u0026nbsp;Child-Pugh score, tumor burden,\u0026nbsp;PVTT\u0026nbsp;type\u0026nbsp;and\u0026nbsp;PLT level. Variables screened for SOR were ECOG score, total tumor diameter, PVTT type, and ALB level.\u0026nbsp;LASSO regression with cross-validation showed that the screening variables were the \u0026nbsp;tumor burden, PVTT type and PLT level.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eBuild different models and compare them\u003c/h2\u003e\n\u003cp\u003eThe\u0026nbsp;multivariate Cox survival regression model and stepwise backward regression\u0026nbsp;were used\u0026nbsp;to determine the final model variables with the minimum AIC.\u0026nbsp;These\u0026nbsp;variables\u0026nbsp;were then modelled using\u0026nbsp;a multivariate Cox survival regression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results showed that\u0026nbsp;the\u0026nbsp;variables\u0026nbsp;from\u0026nbsp;univariate Cox\u0026nbsp;regression screening to be\u0026nbsp;analyzed\u0026nbsp;by multivariate\u0026nbsp;Cox survival regression model were\u0026nbsp;Child Pugh score,\u0026nbsp;tumor burden, PVTT\u0026nbsp;type\u0026nbsp;and PLT level\u0026nbsp;(Model 1). The SOR screening variables were finally analyzed for total tumor diameter and PVTT type (Model 2).\u0026nbsp;The variables selected by LASSO regression\u0026nbsp;with\u0026nbsp;cross-validation did not change after multivariate Cox survival regression model analysis (model 2),\u0026nbsp;including\u0026nbsp;the\u0026nbsp;tumor burden, PVTT type, and PLT level (Model 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn Figure 4, the AUC value of the median overall survival of\u0026nbsp;Model 1 is greater than that of\u0026nbsp;Model 2 and\u0026nbsp;Model 3, therefore,\u0026nbsp;Model 1\u0026nbsp;were chosen.\u003c/p\u003e\n\u003ch2\u003eDevelopment and validation of an\u0026nbsp;individualized\u0026nbsp;prediction model\u003c/h2\u003e\n\u003cp\u003eThe independent predictors associated with Model 1 identified by multivariate Cox regression analysis are shown in Table\u0026nbsp;2.\u0026nbsp;A\u0026nbsp;model that incorporated\u0026nbsp;these\u0026nbsp;independent predictors was developed and presented as\u0026nbsp;a\u0026nbsp;nomogram (Figure 5). The calibration curve for median survival probability\u0026nbsp;showed\u0026nbsp;a moderate level of consistency between the predicted and observed results.\u0026nbsp;For internal\u0026nbsp;validation, the\u0026nbsp;C-index for the prediction nomogram was\u0026nbsp;0.771\u0026nbsp;(95% CI: 0.722-0.820) for the\u0026nbsp;training set, which was confirmed to be 0.758\u0026nbsp;via bootstrapping validation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eK-fold cross-validation is used for external validation.In the K-fold CV procedure , the training set and validation set is randomly and evenly split into K parts. Model 1 is built based on K\u0026nbsp;\u0026minus;\u0026nbsp;1 parts of the training set. Prediction accuracy of this candidate model is then evaluated on K\u0026nbsp;\u0026minus;\u0026nbsp;1 parts of the validation set. By respectively using each of the K parts as the training set and repeating the model building and evaluation procedure, we choose the model with the smallest cross-validation score (the mean squared prediction error MSPE) as the\u0026nbsp;\u0026lsquo;optimal\u0026rsquo;\u0026nbsp;model. Our data was run 1000 times, K is equal to 5.\u0026nbsp;At last, the ultimate model is obtained with its parameter estimates as the average values across K candidate \u0026lsquo;optimal\u0026rsquo; models. At the same time we get the average of 1000 c-indexes\u0026nbsp;(0.744) (Figure 6).\u003c/p\u003e\n\u003ch2\u003eClinical usefulness\u003c/h2\u003e\n\u003cp\u003eThe DCA\u0026nbsp;results for\u0026nbsp;the nomogram\u0026nbsp;are\u0026nbsp;shown in Figure 6. The decision curve demonstrated that if the threshold probability of a patient or physician was\u0026nbsp;25%, using the developed nomogram to predict median survival was more beneficial than using treat-all-patients or treat-none schemes.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAdverse reactions related to TACE and \u003csup\u003e125\u003c/sup\u003eI seed implantation\u003c/h2\u003e\n\u003cp\u003eMost patients experienced mild adverse reactions related to TACE, including abdominal pain, nausea, and vomiting. After 3-7 days of symptomatic treatment, the patient\u0026apos;s symptoms were relieved. No serious adverse reactions related to TACE was observed. \u0026nbsp;Among them, two patients with large intrathoracic gas were treated with closed thoracic drainage. None of the patients experienced any adverse reactions related to surgery.\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003ch2\u003eAnalysis of the curative effect of TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation\u003c/h2\u003e\n\u003cp\u003ePrevious studies have shown that the prognosis of patients with\u0026nbsp;advanced HCC with\u0026nbsp;PVTT is generally poor, and PVTT is\u0026nbsp;a\u0026nbsp;risk\u0026nbsp;factor\u0026nbsp;that\u0026nbsp;affects\u0026nbsp;the survival of patients\u0026nbsp;with HCC (23-25).\u0026nbsp;In this study, TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation was used to treat HCC patients with type II PVTT, and\u0026nbsp;the\u0026nbsp;mOS reached 12.5\u0026nbsp;months, which is similar to previous reports\u0026nbsp;(15-18).\u003c/p\u003e\n\u003cp\u003eIt\u0026nbsp;has been reported that surgical resection may be a treatment for HCC with PVTT\u0026nbsp;(26-28).\u0026nbsp;However,\u0026nbsp;most patients\u0026nbsp;already\u0026nbsp;lose\u0026nbsp;the opportunity\u0026nbsp;to undergo\u0026nbsp;surgical resection by the time\u0026nbsp;the tumor is\u0026nbsp;discovered. Although TACE alone has a certain effect on patients with HCC and PVTT, its effect is often\u0026nbsp;unsatisfactory, with a median survival time of only 7.1 months\u0026nbsp;(29). Owing\u0026nbsp;to obstruction of the portal vein caused by PVTT, reperforming TACE greatly reduces the blood supply to the liver, leading to liver tissue necrosis and liver\u0026nbsp;function\u0026nbsp;failure. Therefore, it is particularly important to control PVTT\u0026nbsp;progression\u0026nbsp;and reduce the occurrence of complete portal vein obstruction. In our study, \u003csup\u003e125\u003c/sup\u003eI seed implantation largely controlled the progress of PVTT, with\u0026nbsp;an\u0026nbsp;ORR\u0026nbsp;of\u0026nbsp;65%. When PVTT is well controlled, the patient\u0026apos;s liver function can be\u0026nbsp;restored\u0026nbsp;to a certain extent. At the same time, a prospective study reported that TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation has a certain effect on maintaining liver function\u0026nbsp;(18).\u0026nbsp;Therefore, for HCC patients with PVTT, it is particularly important to actively control PVTT.\u003c/p\u003e\n\u003cp\u003eRadiotherapy is also an important local treatment\u0026nbsp;for\u0026nbsp;PVTT\u0026nbsp;(8).\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation is as effective as Stereotactic Body Radiation Therapy\u0026nbsp;(SBRT)\u0026nbsp;and Three Dimensional Conformal Radiation Therapy\u0026nbsp;(3DCR)\u0026nbsp;as IR therapy.\u0026nbsp;A\u0026nbsp;randomized, open-label clinical trial to\u0026nbsp;compare\u0026nbsp;the efficacy and safety of TACE combined with radiotherapy and sorafenib in the treatment of liver cancer and large vessel invasion\u0026nbsp;(30)\u0026nbsp;showed that,\u0026nbsp;compared with sorafenib,\u0026nbsp;the former\u0026nbsp;can prolong progression-free survival and overall survival of patients, with\u0026nbsp;an\u0026nbsp;mOS of 13.1 months.\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;PVTT\u0026nbsp;classification is closely related to the prognosis and therapeutic\u0026nbsp;effects\u0026nbsp;of HCC. In our study, we conducted a subgroup analysis of type IIa and type IIb PVTT and compared the\u0026nbsp;difference\u0026nbsp;in survival. The results showed that the mOS of patients with type IIa PVTT was significantly higher than\u0026nbsp;those\u0026nbsp;with type IIb PVTT. This may be because when only one branch of the portal vein is blocked by a\u0026nbsp;tumor\u0026nbsp;thrombus, the liver function is better,\u0026nbsp;and the portal vein pressure is maintained relatively low compared to when both branches of the portal vein are blocked. Patients with type IIa PVTT have better liver function and lower portal pressure than patients with type IIb PVTT; therefore,\u0026nbsp;they can withstand more treatment. Previous studies have\u0026nbsp;shown\u0026nbsp;that type III PVTT is an independent predictor of poor prognosis\u0026nbsp;in\u0026nbsp;such patients. The higher the degree of PVTT\u0026nbsp;(31-33),\u0026nbsp;the worse the treatment effect, which is similar to the results of\u0026nbsp;the present\u0026nbsp;study.\u003c/p\u003e\n\u003ch2\u003eAnalysis and clinical significance of predictive models\u003c/h2\u003e\n\u003cp\u003eIn this study, the results showed that Child-Pugh\u0026nbsp;score, tumor burden,\u0026nbsp;PVTT\u0026nbsp;and PLT\u0026nbsp;level\u0026nbsp;were\u0026nbsp;significant risk factors\u0026nbsp;for\u0026nbsp;OS. The prognostic factors of HCC have been shown to include maximum\u0026nbsp;tumor\u0026nbsp;diameter,\u0026nbsp;tumor\u0026nbsp;type,\u0026nbsp;tumor\u0026nbsp;stage, cirrhosis, Child-Pugh score, AFP level, and serological indicators of liver function\u0026nbsp;(34-36),\u0026nbsp;which are similar to the results of our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe \u0026ldquo;Six and Twelve\u0026rdquo; model proposed in the previous study is an excellent model for HCC treatment with TACE\u0026nbsp;(37).\u0026nbsp;This model\u0026nbsp;indicates\u0026nbsp;that patients with\u0026nbsp;cumulative\u0026nbsp;tumor size \u0026gt; 12 cm have a poor prognosis, and\u0026nbsp;the\u0026nbsp;mOS is only 15.8 months. This study also used the sum of tumor size (cm) and\u0026nbsp;tumor\u0026nbsp;number to evaluate the\u0026nbsp;tumor burden.\u0026nbsp;According to the characteristics of the enrolled patients, the standard deviation of the patient\u0026rsquo;s\u0026nbsp;tumor burden was\u0026nbsp;7.71,\u0026nbsp;indicating\u0026nbsp;that the\u0026nbsp;tumor burden was\u0026nbsp;relatively large. However, it is worth noting that the \u0026quot;Six and Twelve\u0026quot; model does not evaluate vascular metastasis, and the appearance of PVTT undoubtedly increases the\u0026nbsp;tumor burden\u0026nbsp;and\u0026nbsp;patient\u0026nbsp;survival also deteriorate. The models established by the variables screened by different methods are not the same; however,\u0026nbsp;the best model can be selected only on the basis of rigorous statistics based on previous research and practical clinical significance. This shows that even in patients with portal vein metastasis, the use of the sum of\u0026nbsp;maximum tumor diameter and number\u0026nbsp;to evaluate intrahepatic lesions, combined with the treatment of PVTT,\u0026nbsp;can be used\u0026nbsp;for HCC patients with type II PVTT\u0026nbsp;who\u0026nbsp;undergo TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation therapy. According\u0026nbsp;to the prediction model of this study, it is feasible to predict the prognosis of such patients.\u003c/p\u003e\n\u003cp\u003eA unique feature of this study\u0026nbsp;was\u0026nbsp;the development of a\u0026nbsp;personalized\u0026nbsp;predictive model to predict the prognosis of each patient. From the perspective of\u0026nbsp;tumor burden, we constructed a nomogram to predict\u0026nbsp;the\u0026nbsp;mOS and combined the Child-Pugh\u0026nbsp;score\u0026nbsp;and PLT level\u0026nbsp;to predict the prognosis of type II PVTT from more perspectives. Previous studies and discussions\u0026nbsp;have\u0026nbsp;also\u0026nbsp;illustrated\u0026nbsp;the impact of\u0026nbsp;the Child-Pugh score\u0026nbsp;on HCC patients with type II PVTT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimultaneously, we evaluated the model from different angles,\u0026nbsp;conducted external verifications, and obtained good results. In statistical analysis, the general model usually directly brings the validation set input into the training set model to obtain the c-index. This study uses the K-fold CV procedure, and uses cross-validation to achieve multiple c-index calculations. The verification results are more robust than traditional methods\u0026nbsp;(39).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResearch based on TNM staging only focuses on the change in the size of the patient\u0026rsquo;s\u0026nbsp;tumor\u0026nbsp;and whether it has metastasized\u0026nbsp;(38)\u0026nbsp;while ignoring the impact of clinical indicators and the overall patient survival.\u0026nbsp;It is undoubtedly one-sided to consider the survival of patients solely based on\u0026nbsp;tumor\u0026nbsp;status, and the development of the nomogram provides a more comprehensive basis for judgment. At present, the nomogram has been shown to have a certain role in evaluating the prognosis of many cancer patients, including\u0026nbsp;those\u0026nbsp;with HCC\u0026nbsp;and\u0026nbsp;PVTT\u0026nbsp;(40-42).\u0026nbsp;It reflects the characteristics of the\u0026nbsp;tumor\u0026nbsp;and the patient\u0026apos;s state, including additional clinical parameters. Therefore, the nomogram is considered more advantageous than the traditional staging method. Some researchers have proposed it as an alternative method or a new standard for guiding cancer treatment\u0026nbsp;(43).\u003c/p\u003e\n\u003ch2\u003eSecurity and limitations\u003c/h2\u003e\n\u003cp\u003eIn terms of safety, TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation\u0026nbsp;for PVTT\u0026nbsp;is well tolerated, consistent with the results of other studies\u0026nbsp;(15-18).\u003c/p\u003e\n\u003cp\u003eThis study has certain limitations. First, it\u0026nbsp;is a retrospective study with a small sample size, which may\u0026nbsp;have led\u0026nbsp;to selection bias. The results need to be further confirmed\u0026nbsp;in\u0026nbsp;prospective,\u0026nbsp;multicenter, randomized\u0026nbsp;controlled trials. Although\u0026nbsp;the\u0026nbsp;Child-Pugh\u0026nbsp;score, tumor burden,\u0026nbsp;and PVTT type\u0026nbsp;were\u0026nbsp;included in the nomogram as predictors, they\u0026nbsp;showed a\u0026nbsp;good predictive ability.\u0026nbsp;Owing\u0026nbsp;to the small number of indicators included in this study, more effective indicators may not be included. Therefore, the prediction efficiency of the model\u0026nbsp;must\u0026nbsp;be further improved.\u003c/p\u003e\n\u003cp\u003eIn conclusion, there are still controversies about the treatment of PVTT, but most of the current research and clinical practice\u0026nbsp;showed\u0026nbsp;that for\u0026nbsp;HCC\u0026nbsp;patients with PVTT, combined treatment should be used to obtain better treatment results. This study\u0026nbsp;showed\u0026nbsp;that TACE combined with \u003csup\u003e125\u003c/sup\u003eI seed implantation is an effective method for the treatment of HCC with PVTT. Based on the \u0026quot;Six and Twelve\u0026quot; model, combined with the Child-Pugh score and PVTT type, it is a predictive model that can be used to predict mOS in patients with HCC and PVTT receiving treatment.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n \u003cli\u003eMassarweh NN, El-Serag HB. Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control. 2017 Jul-Sep;24(3):1073274817729245. doi: 10.1177/1073274817729245. PMID: 28975830; PMCID: PMC5937247.\u003c/li\u003e\n \u003cli\u003eYang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):589-604. doi: 10.1038/s41575-019-0186-y. Epub 2019 Aug 22. PMID: 31439937; PMCID: PMC6813818.\u003c/li\u003e\n \u003cli\u003eWei X, Jiang Y, Zhang X, et al. 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Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial. J Cancer Res Clin Oncol. 2014; 140(2):211-219. doi: 10.1007/s00432-013-1568-0.\u003c/li\u003e\n \u003cli\u003ePoon R T, Fan S T, Ng I O, et al. Prognosis after hepatic resection for stage IVA hepatocellular carcinoma: a need for reclassification[J]. Ann Surg, 2003,237(3):376-383.\u003c/li\u003e\n \u003cli\u003eKamiyama T, Nakanishi K, Yokoo H, et al. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma[J]. Int J Clin Oncol, 2007,12(5):363-368.\u003c/li\u003e\n \u003cli\u003eZheng N, Wei X, Zhang D, et al. Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus. 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Erratum in: J Clin Oncol. 2016 Jul 10;34(20):2436. PMID: 27138577.\u003c/li\u003e\n \u003cli\u003eLi X, Ye Z, Lin S, Pang H. Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram. BMC Cancer. 2021 Jun 15;21(1):701. doi: 10.1186/s12885-021-08469-1. PMID: 34126955; PMCID: PMC8204556.\u003c/li\u003e\n \u003cli\u003eZhang L, Sun JH, Hou ZH, et al. Prognosis Nomogram for Hepatocellular Carcinoma Patients with Portal Vein Invasion Undergoing Transarterial Chemoembolization Plus Sorafenib Treatment: A Retrospective Multicentre Study. Cardiovasc Intervent Radiol. 2021 Jan;44(1):63-72. doi: 10.1007/s00270-020-02579-2. Epub 2020 Sep 23. PMID: 32965582.\u003c/li\u003e\n \u003cli\u003eIasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008 Mar 10;26(8):1364-70. doi: 10.1200/JCO.2007.12.9791. PMID: 18323559.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;\"\u003eTable 1. Baseline characteristics of patients with type IIa and IIb PVTT in the primary cohort\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:372.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:117.75pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eVariable\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:65.25pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003elevel\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:73.5pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eTraining set\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:73.5pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eValidation set\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.0pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:20.05pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eN\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:20.05pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:20.05pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e97\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:20.05pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:20.05pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eSex\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 85 (87.6)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 49 (87.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 12 (12.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;7 (12.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eAge\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;57.21\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e10.99\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;58.96\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e9.76\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.323\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eECOG\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 39 (40.2)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 27 (48.2)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.427\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 58 (59.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 29 (51.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eChildPugh\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 40 (41.2)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 25 (44.6)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.915\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 30 (30.9)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 16 (28.6)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 27 (27.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 15 (26.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eNumber\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 45 (46.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 22 (39.3)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.317\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e2-4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 40 (41.2)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 22 (39.3)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026ge;5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 12 (12.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 12 (21.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:117.75pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eMaximum tumor diameter\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;font-family: SimSun;color:black;\"\u003e<\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e60 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 60 (61.9)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 36 (64.3)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.900\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026ge;60 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 37 (38.1)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 20 (35.7)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:117.75pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eTotal tumor diameter\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;font-family: SimSun;color:black;\"\u003e<\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e100mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 69 (71.1)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 45 (80.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.285\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026ge;100 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 28 (28.9)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 11 (19.6)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eTumor burden\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 7.71 (3.09)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 8.29 (2.26)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.226\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePosition\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eRight/Left\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 50 (51.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 22 (39.3)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.195\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eBiloba\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 47 (48.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 34 (60.7)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePVTT\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eIIa\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 56 (57.7)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 35 (62.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.683\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eIIb\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 41 (42.3)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 21 (37.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePreoperative AFP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026lt; 400 ng/mL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 58 (59.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 35 (62.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.874\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026ge;400 ng/mL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 39 (40.2)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 21 (37.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePLT (\u0026times;109/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e146.97\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e39.86\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e145.79\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e34.97\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.854\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePT (s)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e13.12\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e13.19\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.36\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.779\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eTBL (umol/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;23.69\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e15.96\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;20.33\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e13.27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.186\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eALB (g/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;38.52\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e5.96\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;37.99\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e4.37\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.564\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 5.31\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e2.25\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 5.37\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.72\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.876\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eRBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 4.32\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.61\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp; \u0026nbsp; 4.45\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.55\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.75pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.201\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eHGB (g/L)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e132.34\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e18.79\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e130.12\u003c/span\u003e\u003cspan style=\"font-size:12px;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e14.38\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.447\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-indent:10.0pt;'\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eUnless otherwise indicated, data are presented as numbers of patients.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-indent:10.0pt;'\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eData are presented as mean (standard deviation)\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:9.0pt;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eAbbreviations: ECOG=Eastern Cooperative Oncology Group; \u0026nbsp;PVTT= portal vein tumor thrombosis; AFP = alpha fetoprotein; PLT=platelet; PT=\u003c/span\u003e\u003cspan style=\"font-size:13px;\"\u003e\u0026nbsp;\u003cspan style=\"color:black;\"\u003eprothrombin time; TBL=\u003c/span\u003e \u003cspan style=\"color:black;\"\u003etotal bilirubin; ALB=\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ealbumin;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eWBC =\u003c/span\u003e\u003cspan style=\"font-size:13px;\"\u003e\u0026nbsp;\u003cspan style=\"color:black;\"\u003ewhite blood cell;\u0026nbsp;\u003c/span\u003eRBC = red \u003cspan style=\"color:black;\"\u003eblood cell; \u0026nbsp;HGB = hemoglobin;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;'\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;\"\u003eTable 2. Risk Factors Affecting Survival in \u0026nbsp;Model 1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:373.5pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:112.5pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eIntercept and Variable\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:39.75pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026beta;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:186.75pt;border:none;border-top: solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eModel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:34.5pt;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eOdds Ratio\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e95% CI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eChild-Pugh Score-6:5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.675\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.994-2.824\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.052\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eChild-Pugh Score-7:5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.598\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.819\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.071-3.088\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.027\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePVTT types\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.356\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e3.881\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e2.340-6.434\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eTumor burden\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.248\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e1.281\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.476-1.010\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePLT\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e-0.006\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.994\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.473-0.992\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.045\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:186.75pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eC-index\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003ePrimary cohort\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.771 (0.722-0.820)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003eValidation cohort\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:center;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e0.744\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"border:none;border-bottom:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style=\"font-size:12px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;font-size:16px;font-family:\"Times New Roman\",serif;margin:0in;text-indent:10.0pt;'\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eNOTE. b is the regression coefficient.\u003c/span\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGrant Support: Technology Major Project of the Ministry of Science and Technology of China (2018ZX10303502). Henan Province Medical Science and Technology Research Project (201701032). Medical Education Research Project of Henan Province\u0026nbsp;(Wjlx2021334). Henan Province Natural Science Foundation (212300410403) .Science and Technology Department of Henan Province (No. 212102310162); Medical Science and Technology Research Project of Henan Province (No. LHGJ20190633).Henan Province Natural Science Foundation (222300420574).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: HTH\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient selection and treatment: XHZ, HLL, LZ, GSC,\u003c/p\u003e\n\u003cp\u003eData collection, analysis and interpretation: XHZ, YZ, SJX, HLL\u003c/p\u003e\n\u003cp\u003eData interpretation: HTH, XHZ, YZ, SXJ, HLL\u003c/p\u003e\n\u003cp\u003eUndertook steering committee activities and critical statistical processing: HTH, YZ\u003c/p\u003e\n\u003cp\u003eManuscript writing:XHZ, YZ\u003c/p\u003e\n\u003cp\u003eManuscript reviewing: HTH\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki, and was approved by the Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University review board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll of the patients sign in the informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\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, portal vein tumor thrombus, 125I seed, TACE, prognostic factors","lastPublishedDoi":"10.21203/rs.3.rs-1355598/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1355598/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: To investigate the efficacy of transhepatic arterial chemoembolization (TACE) combined with 125I seed implantation in patients with first-branch portal vein tumor thrombus (PVTT) hepatocellular carcinoma (HCC), establish a prognostic nomogram to determine the prognosis for individual patients.\u003c/p\u003e\u003cp\u003eMethods: We retrospectively collected 97 cases of TACE combined with 125I seed implantation in our hospital as the primary cohort. The main observation index of the results of the study was the median overall survival (mOS). Univariate analysis, optimal subset regression(OSR) and LASSO regression were used to screen the variables. The selected variables were included in the multivariate Cox survival regression model, and a prognostic nomogram was developed. The performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. The internal and external verifications were evaluated.\u003c/p\u003e\u003cp\u003eResults: The mOS of all patients was 12.5 months. The final determination was made using the Child-Pugh score, tumor burden, PVTT types and PLT level to establish a nomogram prediction model [C -index :0.771 (95% CI: 0.722-0.820)]. The model demonstrated good discrimination and calibration. Application of the nomogram to the external verification data still yielded good discrimination [C-index: 0.744], and good calibration. The decision curve analysis demonstrated that the clinical validity of the model is clinically useful.\u003c/p\u003e\u003cp\u003eConclusion: TACE combined with 125I seed implantation indicated better long-term outcomes in patients with HCC combined with type II PVTT. This nomogram can be used to predict the prognostic survival time of such patients and help doctors make decisions in clinical practice.\u003c/p\u003e","manuscriptTitle":"Construction of a prognostic nomogram for transarterial chemoembolization combined with 125I seed implantation for hepatocellular carcinoma with portal vein tumor thrombus: a multicenter retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2022-06-02 15:16:06","doi":"10.21203/rs.3.rs-1355598/v3","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}},{"code":2,"date":"2022-06-01 16:43:45","doi":"10.21203/rs.3.rs-1355598/v2","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}},{"code":1,"date":"2022-02-25 15:01:50","doi":"10.21203/rs.3.rs-1355598/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":"889ae109-8118-4a74-b69c-784e7086a281","owner":[],"postedDate":"June 2nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-24T08:44:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-02 15:16:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v3","identity":"rs-1355598","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1355598","identity":"rs-1355598","version":["v3"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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