Comparison of Clinical Efficacy of Molecular Targeted Drugs Combined with Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemoembolization Alone for Primary Liver Cancer

Comparison of Clinical Efficacy of Molecular Targeted Drugs Combined with Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemoembolization Alone for Primary Liver Cancer | 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 Comparison of Clinical Efficacy of Molecular Targeted Drugs Combined with Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemoembolization Alone for Primary Liver Cancer Xinru Sun, Bojiang Wang, Yin Zhang, Baodong Liu, Liping Sun, Guangming Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3752571/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : it was to explore the therapeutic value of transcatheter arterial chemoembolization (TACE) combined with molecular targeted drugs (MTD) in patients with primary liver cancer (PLC). Methods : 78 patients with PLC hospitalized in Zibo Central Hospital were randomly grouped. Group A was treated with TACE alone, group B with bevacizumab combined with TACE, and group C with sorafenib combined with TACE, 26 cases in each. The patients were followed up for 1 year, and the clinical efficacy, adverse drug reaction (ADR), laboratory indexes, and survival rate (SR) of the three groups were observed and evaluated. Results : The effective rate and disease control rate of group C were 50% and 69.23%, respectively, which were clearly higher than those of groups A (15.38%, 38.46%) and B (34.61%, 53.84%). There was no obvious distinction in serum Alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels among them before treatment. Following treatment, group C (404.37±12.47 ng/mL; 246.52±38.17 ng/mL) were clearly lower than those in groups A (483.74±13.28 ng/mL, 367.28±47.03 ng/mL) and B (450.28±12.19 ng/mL, 291.72±43.69 ng/mL). The incidence of ADR in group C was generally lower than that in groups A and B, without obvious distinction in ADR of TACE among them. The overall survival time was obviously longer in group C (11.8 months) than in groups A (8.4) and B (10.1). Following 6 months of treatment, SR was not evidently different among them. Following 12 months of treatment, the SR was obviously superior in group C (84.61%) as against groups A (57.69%) and B (73.07%) (P < 0.05). Conclusion : TACE combined with MTD is superior to TACE alone in the treatment of PLC. The efficacy, survival time, and SR of sorafenib are better than those of bevacizumab. PLC TACE MTD sorafenib bevacizumab Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction The incidence rate of PLC is very high in in China, accounting for more than 50% of the world. It can occur in people at any age, people at 40–49 years old is the most, the ratio of men to women is 2–5:1. About 110,000 people die from liver cancer (LC) in China every year, accounting for 45% of LC deaths in the world [ 1 ]. PLC is a cancer disease that occurs in the liver and usually originates from epithelial cells. The most common cause of hepatocellular carcinoma is hepatitis B, which hides in liver cells, and many hepatitis B replication will lead to necrosis and proliferation of liver cells, leading to liver cirrhosis, which will further lead to hepatocellular carcinoma [ 2 , 3 ]. It is generally believed that PLC is related to the following factors: chronic infection, such as viral hepatitis C, viral hepatitis B, liver cirrhosis; external material factors, such as aflatoxin, contaminated water, chemical carcinogens; bad living habits, such as alcoholism, smoking, obesity. Patients with PLC mainly present with persistent upper abdominal pain, accompanied by adverse symptoms such as yellow body surface, loss of appetite, and blue stool [ 4 , 5 ]. The most common detection methods for LC are imaging and tumor markers, which can detect liver lesions at an early stage. PLC focuses on prevention, it should be early detection and treatment, but because LC is often found in the late stage, the prognosis is poor. Surgical resection is the preferred treatment to prolong the survival time of LC patients. Radiofrequency ablation, cryotherapy, and microwave therapy can also be selected for LC. Liver transplantation is feasible when small LC with cirrhosis has no vascular tumor thrombus formation and poor liver function presents [ 6 , 7 ]. For patients with advanced LC or unresectable LC, interventional embolization, radiotherapy, systemic chemotherapy, and immunotherapy can be adopted. TACE is a kind of LC interventional therapy, which refers to a treatment method in which the femoral artery at the root of the thigh of the patient is punctured, a tiny catheter is penetrated, and the catheter is sent to the intrahepatic tumor site under the guidance of the fluoroscopy of the digital subtraction angiography machine. The doctor will inject anti-cancer drugs and embolic agents into the intrahepatic tumor artery through the catheter [ 8 ]. It is suitable for patients with advanced PLC who can’t be surgically resected, and patients who can be surgically resected but can’t or is unwilling to undergo surgery due to old age, severe liver cirrhosis, and other reasons. TACE can not only directly kill tumor cells, but also block tumor blood supply, causing tumor to lose nutrition and die out. Currently, it is the first choice for advanced LC [ 9 ]. TACE has the following advantages: it can treat unresectable advanced hepatocellular carcinoma; The application of interventional therapy before liver tumor resection can reduce the tumor volume, facilitate the second-stage resection, and determine the number of lesions. Local pain, bleeding, and arteriovenous fistula were controlled. Some patients with large tumors have a high risk of postoperative recurrence. Preventive intervention can be performed about 1 month after surgery to kill possible residual active lesions and reduce the recurrence rate. However, TACE alone has limited improvement in survival and poor long-term efficacy [ 10 , 11 ]. In the 21st century, tumor therapy has entered the era of molecular targeted therapy. Molecular targeted therapy refers to the key macromolecules in the process of tumor occurrence and development, including cell signal transduction and other biological pathway targets involved in the process of tumor development, by specifically blocking the signal transduction of tumor cells to control their gene expression and change biological behavior. It also can prevent tumor angiogenesis through resistance, thereby inhibiting the growth and reproduction of tumor cells and exerting anti-tumor effects [ 12 – 14 ]. The molecular pathogenesis of tumor cells is complex, which often leads to liver cirrhosis after tissue damage and induces mutations in liver cells at the gene level. The formation, progression, and metastasis of LC are closely correlated with varieties of gene mutations and cell signaling pathways, including the activation of abnormal growth factors and the continuous activation of cell division signaling pathways, anti-apoptosis signaling pathway disorders, and abnormal angiogenesis. The complex molecular pathogenesis of LC suggests that there are multiple potential therapeutic targets, and these targets are the theoretical basis for molecular targeted therapy [ 15 – 17 ]. In recent years, some MTD have made some progress in the research and clinical application of LC. (1) Epidermal growth factor receptor inhibitors. It belongs to the transmembrane glycoprotein family with ligand-dependent tyrosine kinase activity, which is overexpressed in kinds of tumors and is often associated with high tumor invasiveness, rapid progression, and poor prognosis. The representative drugs are gefitinib and erlotinib [ 18 , 19 ]. (2) Anti-angiogenic agents. Neovascularization is considered as a key factor for tumor growth, which not only provides nutrients and oxygen for tumors, but also serves as a pathway for tumor cells to enter the systemic circulation and metastasis. The research on the mechanism of tumor angiogenesis and the treatment of tumor by inhibiting angiogenesis has become a research hotspot in tumor treatment, and anti-angiogenic drugs targeting tumor angiogenesis, such as human recombinant endostatin and human recombinant anti-vascular endothelial growth factor monoclonal antibody bevacizumab, have been adopted in clinical practice [ 20 , 21 ]. Combination with chemotherapy for advanced malignant tumors has achieved exciting clinical results. (3) Multikinase inhibitors. For example, sorafenib, an oral multikinase inhibitor, can inhibit tumor cell proliferation and tumor angiogenesis, which can play a dual role of anti-angiogenesis and anti-tumor cell proliferation at the same time [ 22 , 23 ]. 78 patients with PLC were grouped and given different treatment methods for observation and follow-up, to explore the clinical efficacy of TACE combined with MTD on PLC patients, and to provide reference for the selection of PLC treatment plans. 2. Materials and methods 2.1 Subjects 78 patients with PLC who were hospitalized in Zibo Central Hospital from February 2020 to November 2021 were enrolled, aged 44–68 years, including 47 men and 31 women. There were groups A, B, and C, 26 patients in each group. Group A was given with TACE alone, group B with bevacizumab combined with TACE, and group C with sorafenib combined with TACE. Inclusion criteria: clinical diagnosis and staging criteria were consistent with the 2017 edition of the Standard of Diagnosis and Treatment of Primary Liver Cancer; Liver function was classified as Child-Pugh grades A and B (Table 1 ). Tumor node metastasis classification (TNM) stage Ⅱ-Ⅲ (Table 2 ); Patients without other serious organic diseases; the predicted survival time was 6 months or more. Exclusion criteria: patients who had other malignant tumors; patients with a history of chemotherapy or steroid therapy before surgery. patients unable to complete TACE for various reasons; severe liver dysfunction (liver function grade C), such as severe jaundice, massive ascites or severe cirrhosis, portal hypertension with retrograde blood flow and complete obstruction of the main portal vein, white blood cell < 3,000 or systemic extensive metastasis and multiple organ failure; TNM stage was Ⅳ. With approval of the ethics committee of Zibo Central Hospital, the patients and their families were informed of all related matters of the experiment, all of them signing the informed consent. Table 1 Child-Pugh classification of liver function Parameters 1 point 2 points 3 points Stage of encephalopathy 0 No 1–2 Moderate 3–4 Severe Ascitic fluid No Mild/moderate Severe/refractory Bilirubin (mg/dL) 3.0 (mol/L) 50 (g/dL) > 3.5 2.8–3.5 35 28–35 < 28 PT extension (seconds) 6 INR 2.3 Child-Pugh score Grade A: 5–6 Grade B: 7–9 Grade C: 10–15 T-primary tumor. TX: primary tumor could not be evaluated; T0: no evidence of primary tumor; T1: single tumor without vascular invasion; T2: single or multiple tumors with vascular invasion, the largest of which was less than 5 cm in diameter; T3: multiple tumors, maximum diameter > 5 cm, or tumor involving one portal vein or major branch of hepatic vein; T4: the tumor directly invaded the surrounding organs (except gallbladder), or had penetrated the visceral peritoneum. N-regional lymph node (RLN). NX: RLN metastasis could not be evaluated; N0: no RLN metastasis; N1: presence of RLN metastasis. M- distant metastasis (DM). MX: DM could not be evaluated; M0: no DM; M1: There was DM. Table 2 TNM staging criteria Ⅰ T1 N0 M0 Ⅱ T2 N0 M0 ⅢA T3 N0 M0 ⅢB T4 N0 M0 ⅢC Any T N1 M0 Ⅳ Any T Any N M0 2.2 TACE Before operation: psychological care was given to the patients, and preoperative examinations were completed according to the doctor’s advice, such as blood routine, coagulation time, liver, and kidney function, five items of hepatitis B, electrocardiogram, chest X-ray, etc. Before operation, the patients were given short time of breath holding training and adaptive training such as defecation and urination in bed. contrast media, chemotherapeutic agents, embolic agents (commonly used iodized oil and gelatin sponge), anti-allergic drugs, sandbags (patients can also bring their own salt bags), heparin, etc. were prepared. The skin of the patient’s bilateral groin and surgical field was routinely prepared, containing the skin of both sides of the perineum and the upper 1/2 of the thigh below the pubic symphysis of the lower abdomen. A light, nutrient-rich diet was taken for 1–2 d, and fasting and water deprivation were performed for 6 h before surgery. The bladder was emptied, and sedatives and analgesics should be prescribed half an hour before surgery. Procedure: Puncture was made in the femoral artery 1 cm-3 cm below the midpoint of the inguinal ligament at the point where the pulsation was most obvious. After local anesthesia, the skin was punctured, and a special catheter was inserted into the femoral artery, then into the abdominal aorta, finally into the hepatic artery, and as far as possible into the arterial branches that supply blood to the LC tissue. Embolic agents and chemotherapeutic agents were then infused into the hepatic artery. Following operation, post-embolism syndrome may occur due to the sudden reduction of hepatic arterial blood supply. Corresponding nursing should be done: patients should try to breathe deeply and take oxygen if necessary to improve blood oxygen partial pressure, which was beneficial to the metabolism of liver cells; patients were fasted for 2–3 d and gradually transitioned to a liquid diet, paying attention to frequent meals and less amount to reduce nausea and vomiting. The puncture site was compressed to stop bleeding, and the hematoma and oozing blood were observed. The pulse, blood pressure, pulse of the dorsal foot artery, and the temperature and color of the skin of the affected limb were observed. If the body temperature exceeds 39℃, it should report to the doctor for treatment. Those with high fever should take cooling measures to avoid body consumption. If patients have different degrees of abdominal pain, it is usually caused by the stimulation of the liver capsule or peritoneum by chemotherapy drugs. The location, nature, and degree of abdominal pain should be closely observed. If the pain is severe, the doctor should be reported for appropriate application of analgesic drugs. Due to the action of high concentration of chemotherapy drugs, it stimulated the gastrointestinal tract and caused nausea and vomiting. The patient was instructed to drink plenty of water to eliminate drug metabolites and bacterial toxins. Some patients reacted strongly and vomited, which should be immediately followed by mouthwash with water. In terms of diet, patients were instructed to eat less irritating food, and those who could eat were encouraged to eat light and easy to digest high-protein and high-vitamin diet. Those who could not eat or had obvious reactions were given infusion support treatment. Treatment was usually repeated every 6–8 weeks. 2.3 MTD therapy (1) Patients in group B underwent skin testing for bevacizumab and received a transcatheter arterial infusion of bevacizumab (Avastin, Roche, Basel, Switzerland, approval number: S20120068) at a dose of 4–6 mg·kg before the first TACE. (2) Patients in group C received oral administration of sorafenib (Sorafenib Tosylate, Bayer Pharma AG, Leverkusen, Germany, approval number: HJ20160201), 400 mg, twice daily, 3 to 5 d after the initial TACE. During the treatment, the patients were closely observed for ADR, and the severe patients needed to reduce the dose or stop the drug. All the patients were treated for 6 weeks. 2.4 Follow-up and observation indicators Patients in the three groups came to the outpatient clinic every 5–6 weeks for reexamination, and the follow-up period was 1 year. Patients who died from any cause, lost to follow-up, or reached the follow-up time were regarded as the end of the observation. Observation indicators were as follows. (1) Clinical efficacy: The clinical efficacy evaluation criteria of tumors are shown in Table 3 , and the treatment response rate (CR + PR) and disease control rate (CR + PR + SD) were calculated. Overall survival, defined as the time between the initial diagnosis and death from any cause or loss to follow-up, was examined. (2) ADR: According to the WHO classification standard for common adverse reactions of anticancer drugs (Table 4 ), the ADR of patients following treatment was observed and recorded. (3) Laboratory indicators: the serum levels of AFP and CEA were observed and recorded before and following treatment. (4) SR: the survival number of patients at 6 months and 12 months following treatment was observed and recorded. SR was computed: (number of survivors in each group/total number in each group) ×100%. Table 3 Criteria for efficacy evaluation Evaluation Definition (Complete response) CR All the target lesions disappeared. (Partial response) PR The sum of the maximum diameters of baseline lesions was reduced by at least 30%. (Stable disease) SD The sum of the maximum diameters of baseline lesions decreased or increased but did not reach PR. (Progressive disease) PD The sum of the maximum diameters of baseline lesions increasing at least 20% or new lesions appearing. Table 4 WHO classification for common toxicity and side effects of anticancer drugs Indicators 0 Ⅰ Ⅱ Ⅲ Ⅳ Hb (g/L) ≥ 110 95–109 80–94 65–79 ༜65 WBC (×109/L) ≥ 4.0 3.0-3.9 2.0-2.9 1.0-1.9 ༜1.0 Granulocytes (×109/L) ≥ 2.0 1.5–1.9 1.0-1.4 0.5–0.9 ༜0.5 Platelets (×109/L) ≥ 100 75–99 50–74 25–49 ༜25 Bleeding No Petechiae Mild bleeding Obvious bleeding Severe bleeding Bilirubin (×N) ≤ 1.25 1.26–2.5 2.6-5.0 5.1–10.0 ༞10 Alanine aminotransferase (×N) ≤ 1.25 1.26–2.5 2.6-5.0 5.1–10.0 ༞10 Alkaline phosphatase (×N) ≤ 1.25 1.26–2.5 2.6-5.0 5.1–10.0 ༞10 Oral cavity No abnormality Erythema and pain Erythema, ulcers, able to eat Ulcers, only liquid diet Unable to eat Nausea and vomiting No Nausea Temporary vomiting Vomiting, requiring treatment Uncontrollable vomiting Diarrhea No Transient ( 2 d) Needing treatment Bloody diarrhea Urea nitrogen (×N) ≤ 1.25 1.26–2.5 2.6-5.0 5.1–10.0 ༞10 Creatinine (×N) ≤ 1.25 1.26–2.5 2.6-5.0 5.1–10.0 ༞10 Proteinuria No + ++, +++ ++++ Nephrotic syndrome Hematuria No Hematuria under microscopy Severe hematuria Hematuria with blood clots Urinary obstruction Lung No symptoms Mild symptoms Dyspnea following activity Difficult to breath at rest Staying in bed Fever No > 38℃ 38–40℃ > 40℃ The fever was accompanied by hypotension Allergy No Edema Bronchospasm, without treatment Bronchospasm, needing injection treatment Allergic reaction Skin No Erythema Dry desquamation, blisters, and itching Wet dermatitis, ulcers Exfoliative dermatitis, necrosis, surgery required Hair No Mild hair loss Moderate, patchy hair loss Complete hair loss, regrowth Hair loss, no regrowth Special Site infection No Mild infection Moderate infection Severe infection Severe infection with hypotension Rhythm Normal Sinus tachycardia Atrial arrhythmia Multifocal premature ventricular contractions Ventricular arrhythmia Cardiac function Normal Abnormal cardiac presences Transient cardiac insufficiency needing no therapy Cardiac insufficiency, effective therapy Heart failure, and no response to therapy Pericarditis No Pericardial effusion, asymptomatic There are symptoms, but fluid aspiration is not required The pericardial tamponade required fluid aspiration Cardiac tamponade, requiring surgery Consciousness Clear Short-time sleepiness The duration of drowsiness was less than 50% of wakefulness The duration of drowsiness exceeds 50% of wakefulness Coma Peripheral nerves Normal Sensory abnormalities or tendon reflex decreasing Heavy paresthesia or mildly weak Unbearable paresthesia or obvious motion impairment Paralysis Constipation No Mildly Moderately Flatulence Abdominal distension and vomiting Pain No Mildly Moderately Serious Difficult to control Note: N = upper limit of normal value 2.5 Statistical analysis All experimental data were statistically analyzed by SPSS 24.0 software, measurement data were presented as mean + standard deviation ( \(\overline{\text{x}}\) ±s), count data were statistically inferred by χ2 test, survival follow-up was computed and the curve was drawn by Kaplan-Meier method, and Log-rank test was adopted for contrast. P < 0.05 was considered statistically meaningful. 3. Results 3.1 Comparison of clinical efficacy As illustrated in Figures 1 and 2, the effective rate in group A was 15.38%, and the disease control rate was 38.46%. Those in group B were 34.61% and 53.84%, which was superior; and those were higher in group C (50% and 69.23%) (P 0.05), but the serum AFP level was inferior in group C following treatment (P < 0.05) (Figure 3). 3.3 Comparison of ADR As given in Tables 5 and 6, in terms of ADR, the occurrence probability of group C was generally lower than that of group B. However, in terms of ADR of TACE, there was little difference among the three groups. Table 5 ADR of the two groups Clinical manifestations Group B (n=26) Group C (n=26) Bleeding 4 (15.38%) 3 (11.53%) Oral cavity 5 (19.23%) 3 (11.53%) Nausea and vomiting 8 (30.76%) 6 (23.07%) Diarrhea 9 (34.61%) 7 (26.92%) Fever 14 (53.84%) 10 (38.46%) Allergy 10 (38.46%) 7 (26.92%) Constipation 15 (57.69%) 12 (46.15%) Pain 11 (42.3%) 10 (38.46%) Table 6 ADR of TACE Clinical manifestations Group A (n=26) Group B (n=26) Group C (n=26) P Local hematoma 5 (19.23%) 4 (15.38%) 4 (15.38%) 0.526 Local swelling pain 8 (30.76%) 6 (23.07%) 7 (26.92%) 0.635 Nausea and vomiting 10 (38.46%) 11 (42.3%) 10 (38.46%) 1.087 Fever 9 (34.61%) 7 (26.92%) 8 (30.76%) 0.462 Ascites 7 (26.92%) 5 (19.23%) 4 (15.38%) 1.052 Bone marrow suppression 1 (3.84%) 1 (3.84%) 1 (3.84%) 0.678 Pleural effusion 1 (3.84%) 1 (3.84%) 0 0.252 Hepatorenal syndrome 2 (7.69%) 2 (7.69%) 1 (3.84%) 0.623 3.4 Contrast of survival time The overall survival time was 8.4 months in group A, 10.1 months in group B, and 11.8 months in group C. The overall survival time of group C was longer (P 0.05). 12 months following treatment, the number of survivors was lower in groups A (15/26) and B (19/26) than in group C (22/26). The SR was superior in group C (84.61%) as against other two (57.69%), (73.07%) (P < 0.05) (Figure 6). 4. Discussion The liver is the only organ in the human body with complex structure and function, which is supplied by two sets of blood systems. The portal vein, formed by the confluence of venous blood collected from the spleen, pancreas, and intestine, constitutes 75% of the blood supply of liver and is rich in nutrients but low in oxygen. The proper hepatic artery is a branch of the celiac trunk artery and supplies 25% of the blood to the liver. The hepatic artery is arterial blood, which is rich in oxygen but low in nutrients. The blood from the portal vein and hepatic artery pools into the hepatic vein following passing through the hepatic capillary network. The hepatic vein drains into the inferior vena cava and then returns to the heart [ 24 ]. During LC, more than 90–95% of the cancer tissue was supplied by the hepatic artery and less than 10% by the portal vein. Hepatic artery embolization leads to interruption or reduction of blood supply to the tumor, followed by tumor necrosis and shrinkage. TACE is an important treatment method for advanced LC. Generally, the common femoral artery is puncture, and the catheter is passed through the abdominal aorta, celiac trunk, common hepatic artery, and proper hepatic artery to the LC blood supply target artery. Chemoembolization was carried out by injecting the mixture of chemotherapeutic drugs and embolic agents [ 25 ]. 78 patients with PLC were enrolled and treated with TACE. The clinical treatment and survival time were evaluated. It suggested that after TACE, the patients achieved a certain treatment efficiency and disease control rate, the serum AFP and CEA levels were lower than those before treatment, and the overall survival time was more than 8 months. It indicates that TACE has a relatively obvious therapeutic outcome on PLC. Ando et al. (2021) [ 26 ] evaluated the efficacy and safety of TACE in patients with advanced hepatocellular carcinoma. It was found that the median survival time of the patients was 11.6 months, which was clearly superior as against other therapies. For patients with advanced hepatocellular carcinoma, TACE can provide deep response and good prognosis. Its advantage is to embolize the blood supply artery of the tumor, resulting in ischemia, hypoxia, and necrosis of the tumor tissue. On the other hand, by increasing the concentration of local tumor drug and prolonging the contact time between drug and tumor tissue, the curative outcome is evidently improved compared with simple perfusion chemotherapy and simple embolization. However, TACE also has some ADR. Following treatment, patients have a series of ADR such as local hematoma, local pain, nausea and vomiting, with no obvious difference. Arslan and Degirmencioglu (2019) [ 27 ] evaluated ADR in patients with PLC after TACE and found that liver abscess formation was observed in 4 of 163 patients (2.4%) following treatment. Among 313 cases treated with chemoembolization, 4 cases (1.3%) had liver abscess. In addition, biliary-enteric anastomosis was found in two patients, and diabetes mellitus was found in two patients. Doctors should be aware of some complications caused by TACE because of the possibility of worsening the patient’s condition or death. Most LC patients have insidious onset, and early diagnosis is difficult. At diagnosis, LC is locally advanced or has DM, and the surgical resection rate is low. Accurate combination therapy and reasonable sequential therapy can improve the objective response rate, progression-free survival time, and overall survival time of patients. MTD therapy is to use MTD to efficiently and selectively interfere or block cancer cell growth signal transduction pathways, to inhibit the growth of LC cells and reduce the toxic and side effects of drugs on normal tissue cells. Patients in group A were given with TACE alone, patients in group B with bevacizumab combined with TACE, and patients in group C with sorafenib combined with TACE. After comprehensive evaluation, the results revealed that the clinical efficacy, laboratory indexes, survival time, and SR of group C adopting sorafenib were better than those of group A, and were superior than those of group B adopting bevacizumab. Bevacizumab can bind to the free vascular endothelial growth factor in the blood, inhibit the formation of tumor neovascularization, and normalize tumor blood vessels [ 28 ]. Sorafenib is a small molecule receptor tyrosine kinase inhibitor, which belongs to one of the targeted drugs. It can act on tumor cells and tumor blood vessels at the same time, and has a good dual anti-tumor effect. It is often adopted in the adjuvant treatment of advanced LC [ 29 ]. It was confirmed that sorafenib is valid and safe in advanced LC [ 30 , 31 ]. Bevacizumab monotherapy is effective in the treatment of LC, and the results of bevacizumab combined with chemotherapy drugs or other molecular targeted therapy drugs are encouraging. It meant that the treatment of LC has made a breakthrough progress. However, there is still a long way to go for the treatment of PLC because the objective efficacy is still low, the drug price is expensive, and there is no effective method to accurately predict the efficacy or screen the advantageous population. 5. Conclusion By observation and evaluation, the clinical efficacy of MTD combined with TACE for PLC is better than that of TACE alone. The efficacy, survival time, and SR of sorafenib were better as against bevacizumab. The limitation is that the sample size is not large enough and the source is single. The sample size will be expanded, the effect of combination of multiple MTD should be focused on, and the best usage, dosage, and course of combined therapy should be further clarified to explore the best treatment plan for PLC. In addition, according to the individual differences and genetic polymorphisms of patients, it can find molecular biological markers that can predict the efficacy and toxicity of different MTD, individualized treatment for specific tumor patients to obtain the best treatment outcome with the least economic cost. It provides some reference for the clinical treatment of PLC. Declarations Data availability The figures and tables used to support the findings of this study are included in the article. Conflicts of interest The authors declare that they have no conflicts of interest. Funding statement This work was not supported by any funds. Acknowledgements The authors would like to show sincere thanks to those techniques who have contributed to this research. Ethics approval This article does not contain any studies with human participants or animals performed by any of the authors. With approval of the ethics committee of Zibo Central Hospital, the patients and their families were informed of all related matters of the experiment, all of them signing the informed consent. Consent for publication The patients have given their consent for publication. Author contributions Xinru Sun and Bojiang Wang, were major contributors in writing the manuscript. Yin Zhang and Baodong Liu, collected the data. BLiping Sun and Guangming Huang realized the scarcity of the two cases, did literature searches, and revised the manuscript. All authors read and approved the final manuscript. References Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, Laversanne M, McGlynn KA, Soerjomataram I. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022 Dec;77(6):1598-1606. doi: 10.1016/j.jhep.2022.08.021. Epub 2022 Oct 5. PMID: 36208844; PMCID: PMC9670241. Zajkowska M, Mroczko B. Chemokines in Primary Liver Cancer. Int J Mol Sci. 2022 Aug 9;23(16):8846. doi: 10.3390/ijms23168846. PMID: 36012108; PMCID: PMC9408270. MD Yang, Chen X L , Hu X Q , et al. Traditional Chinese medicine syndromes distribution in colorectal cancer and its association with Western Medicine Treatment and Clinical Laboratory Indicators. World Journal of Traditional Chinese Medicine, 2019, 5(2):0-0. Mejia JC, Pasko J. Primary Liver Cancers: Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma. Surg Clin North Am. 2020 Jun;100(3):535-549. doi: 10.1016/j.suc.2020.02.013. Epub 2020 Apr 16. PMID: 32402299. Macias RIR, Monte MJ, Serrano MA, González-Santiago JM, Martín-Arribas I, Simão AL, Castro RE, González-Gallego J, Mauriz JL, Marin JJG. Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics. Aging (Albany NY). 2021 Oct 11;13(19):23416-23434. doi: 10.18632/aging.203620. Epub 2021 Oct 11. PMID: 34633987; PMCID: PMC8544321. Pham L, Kyritsi K, Zhou T, Ceci L, Baiocchi L, Kennedy L, Chakraborty S, Glaser S, Francis H, Alpini G, Sato K. The Functional Roles of Immune Cells in Primary Liver Cancer. Am J Pathol. 2022 Jun;192(6):826-836. doi: 10.1016/j.ajpath.2022.02.004. Epub 2022 Mar 23. PMID: 35337836; PMCID: PMC9194651. Wege H, Schulze K, von Felden J, Calderaro J, Reig M; rare liver tumors working group of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Rare variants of primary liver cancer: Fibrolamellar, combined, and sarcomatoid hepatocellular carcinomas. Eur J Med Genet. 2021 Nov;64(11):104313. doi: 10.1016/j.ejmg.2021.104313. Epub 2021 Aug 18. PMID: 34418585. Uchida-Kobayashi S, Kageyama K, Takemura S, Matsumoto K, Odagiri N, Jogo A, Kotani K, Kozuka R, Motoyama H, Kawamura E, Hagihara A, Yamamoto A, Fujii H, Tanaka S, Enomoto M, Tamori A, Miki Y, Kubo S, Kawada N. Efficacy of rechallenge transcatheter arterial chemoembolization after lenvatinib treatment for advanced hepatocellular carcinoma. JGH Open. 2022 Sep 21;6(11):754-762. doi: 10.1002/jgh3.12819. PMID: 36406645; PMCID: PMC9667401. Nouso K, Wakuta A, Kariyama K. Combination therapy of transcatheter arterial chemoembolization with axitinib for the treatment of inoperable hepatocellular carcinoma. Ann Transl Med. 2020 Aug;8(16):1039. doi: 10.21037/atm.2020.03.198. PMID: 32953839; PMCID: PMC7475487. Onishi H, Nouso K, Takaki A, Oyama A, Adachi T, Wada N, Takeuchi Y, Shiraha H, Okada H. History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients. Acta Med Okayama. 2022 Dec;76(6):695-703. doi: 10.18926/AMO/64120. PMID: 36549772. Moriya T, Kawakami N, Wakai Y, Saito H, Saito K. Pulmonary lipiodol embolism following transcatheter arterial chemoembolization. Respirol Case Rep. 2020 Oct 22;8(9):e00678. doi: 10.1002/rcr2.678. PMID: 33117542; PMCID: PMC7581978. Lu X, Paliogiannis P, Calvisi DF, Chen X. Role of the Mammalian Target of Rapamycin Pathway in Liver Cancer: From Molecular Genetics to Targeted Therapies. Hepatology. 2021 Jan;73 Suppl 1(Suppl 1):49-61. doi: 10.1002/hep.31310. Epub 2020 Dec 3. PMID: 32394479; PMCID: PMC7655627. Huang A, Garraway LA, Ashworth A, Weber B. Synthetic lethality as an engine for cancer drug target discovery. Nat Rev Drug Discov. 2020 Jan;19(1):23-38. doi: 10.1038/s41573-019-0046-z. Epub 2019 Nov 11. PMID: 31712683. Barbosa R, Acevedo LA, Marmorstein R. The MEK/ERK Network as a Therapeutic Target in Human Cancer. Mol Cancer Res. 2021 Mar;19(3):361-374. doi: 10.1158/1541-7786.MCR-20-0687. Epub 2020 Nov 2. PMID: 33139506; PMCID: PMC7925338. Guterres AN, Villanueva J. Targeting telomerase for cancer therapy. Oncogene. 2020 Sep;39(36):5811-5824. doi: 10.1038/s41388-020-01405-w. Epub 2020 Jul 30. PMID: 32733068; PMCID: PMC7678952. Balon K, Sheriff A, Jacków J, Łaczmański Ł. Targeting Cancer with CRISPR/Cas9-Based Therapy. Int J Mol Sci. 2022 Jan 5;23(1):573. doi: 10.3390/ijms23010573. PMID: 35008996; PMCID: PMC8745084. Perez SM, Brinton LT, Kelly KA. Plectin in Cancer: From Biomarker to Therapeutic Target. Cells. 2021 Aug 30;10(9):2246. doi: 10.3390/cells10092246. PMID: 34571895; PMCID: PMC8469460. Lev S. Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis. Biochem Soc Trans. 2020 Apr 29;48(2):657-665. doi: 10.1042/BST20191055. PMID: 32311020. Nogami N, Barlesi F, Socinski MA, Reck M, Thomas CA, Cappuzzo F, Mok TSK, Finley G, Aerts JG, Orlandi F, Moro-Sibilot D, Jotte RM, Stroyakovskiy D, Villaruz LC, Rodríguez-Abreu D, Wan-Teck Lim D, Merritt D, Coleman S, Lee A, Shankar G, Yu W, Bara I, Nishio M. IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2022 Feb;17(2):309-323. doi: 10.1016/j.jtho.2021.09.014. Epub 2021 Oct 7. PMID: 34626838. Kelley RK. Atezolizumab plus Bevacizumab - A Landmark in Liver Cancer. N Engl J Med. 2020 May 14;382(20):1953-1955. doi: 10.1056/NEJMe2004851. PMID: 32402168. Antoniotti C, Vetere G, Cremolini C. FOLFOXIRI plus bevacizumab in the treatment of metastatic colorectal cancer patients with unresectable liver metastases. Ann Transl Med. 2022 Sep;10(18):952. doi: 10.21037/atm-22-3656. PMID: 36267710; PMCID: PMC9577793. Jaffar Ali D, He C, Xu H, Kumaravel S, Sun B, Zhou Y, Liu R, Xiao Z. Microvesicles mediate sorafenib resistance in liver cancer cells through attenuating p53 and enhancing FOXM1 expression. Life Sci. 2021 Apr 15;271:119149. doi: 10.1016/j.lfs.2021.119149. Epub 2021 Feb 4. PMID: 33549596. González R, Rodríguez-Hernández MA, Negrete M, Ranguelova K, Rossin A, Choya-Foces C, Cruz-Ojeda P, Miranda-Vizuete A, Martínez-Ruiz A, Rius-Pérez S, Sastre J, Bárcena JA, Hueber AO, Padilla CA, Muntané J. Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer. Redox Biol. 2020 Jul;34:101528. doi: 10.1016/j.redox.2020.101528. Epub 2020 Apr 4. PMID: 32388267; PMCID: PMC7210585. Agopian VG, Yang JD, Zhu Y, You S, Tseng HR. Early detection of primary liver cancer using plasma cell-free DNA fragmentomics: Do all the pieces come together? Hepatology. 2022 Aug;76(2):289-291. doi: 10.1002/hep.32396. Epub 2022 Mar 14. PMID: 35124841. Seager MJ, Jakobs TF, Sharma RA, Bandula S. Combination of ablation and embolization for intermediate-sized liver metastases from colorectal cancer: what can we learn from treating primary liver cancer? Diagn Interv Radiol. 2021 Sep;27(5):677-683. doi: 10.5152/dir.2021.20520. PMID: 34318754; PMCID: PMC8480946. Ando Y, Kawaoka T, Amioka K, Naruto K, Ogawa Y, Yoshikawa Y, Kikukawa C, Kosaka Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Fukuhara T, Mori N, Takaki S, Tsuji K, Nonaka M, Hyogo H, Aisaka Y, Masaki K, Honda Y, Moriya T, Naeshiro N, Takahashi S, Imamura M, Chayama K, Aikata H. Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma. Oncology. 2021;99(8):507-517. doi: 10.1159/000515865. Epub 2021 May 4. PMID: 33946070. Arslan M, Degirmencioglu S. Liver abscesses after transcatheter arterial embolization. J Int Med Res. 2019 Mar;47(3):1124-1130. doi: 10.1177/0300060518816875. Epub 2019 Jan 7. PMID: 30614336; PMCID: PMC6421372. Mettu NB, Ou FS, Zemla TJ, Halfdanarson TR, Lenz HJ, Breakstone RA, Boland PM, Crysler OV, Wu C, Nixon AB, Bolch E, Niedzwiecki D, Elsing A, Hurwitz HI, Fakih MG, Bekaii-Saab T. Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e2149040. doi: 10.1001/jamanetworkopen.2021.49040. PMID: 35179586; PMCID: PMC8857687. Gnocchi D, Castellaneta F, Cesari G, Fiore G, Sabbà C, Mazzocca A. Treatment of liver cancer cells with ethyl acetate extract of Crithmum maritimum permits reducing sorafenib dose and toxicity maintaining its efficacy. J Pharm Pharmacol. 2021 Sep 7;73(10):1369-1376. doi: 10.1093/jpp/rgab070. PMID: 34014301. Randrian V, Pernot S, Le Malicot K, Catena V, Baumgaertner I, Tacher V, Forestier J, Hautefeuille V, Tabouret-Viaud C, Gagnaire A, Mitry E, Guiu B, Aparicio T, Smith D, Dhomps A, Tasu JP, Perdrisot R, Edeline J, Capron C, Cheze-Le Rest C, Emile JF, Laurent-Puig P, Bejan-Angoulvant T, Sokol H, Lepage C, Taieb J, Tougeron D. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer. Dig Liver Dis. 2022 Jul;54(7):857-863. doi: 10.1016/j.dld.2022.04.024. Epub 2022 May 21. PMID: 35610167. Fan B, Zhang Y, Guo S. Imaging Diagnosis of Primary Liver Cancer Using Magnetic Resonance Dilated Weighted Imaging and the Treatment Effect of Sorafenib. Comput Math Methods Med. 2022 Jun 28;2022:8586943. doi: 10.1155/2022/8586943. PMID: 35799672; PMCID: PMC9256338. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-3752571","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264520032,"identity":"d10df814-fed7-4c09-a27b-78bc1f980ab0","order_by":0,"name":"Xinru Sun","email":"","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinru","middleName":"","lastName":"Sun","suffix":""},{"id":264520033,"identity":"b9bb3c77-4643-4730-a50e-494655ed684f","order_by":1,"name":"Bojiang Wang","email":"","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bojiang","middleName":"","lastName":"Wang","suffix":""},{"id":264520034,"identity":"d19dbfc1-2d13-46d8-af26-be8604f089c9","order_by":2,"name":"Yin Zhang","email":"","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yin","middleName":"","lastName":"Zhang","suffix":""},{"id":264520035,"identity":"89db514a-1cb4-43e9-b15b-2a1465b7d93b","order_by":3,"name":"Baodong Liu","email":"","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Baodong","middleName":"","lastName":"Liu","suffix":""},{"id":264520036,"identity":"6587e6cd-8def-4ea9-adad-344e3a34e372","order_by":4,"name":"Liping Sun","email":"","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Sun","suffix":""},{"id":264520037,"identity":"ac6cc7dc-67ed-4d0d-b6f0-ae15b342b1f3","order_by":5,"name":"Guangming Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PMQrCMBSA4RceJEvQtVDQK0QEtVh6lhYhLg56AS0UOhXnHsMjiEEnDyDoJri4FFwUHEwdxKnNKJh/CAm8LyQANtsPJoDEWG4aTC+F8ANDEgJQDUk+lSMDAvAhyIsNietI31XJdXZXLYq4c32xRmBqu6oi3jJKh3mouhSpdCfi1AAu5aHyYXuSdnmoohR57zgRFwSH94zI4k0GQpHYgCRnTUJaEjAhXkb0/XLcSZGOH5mQI1r3lz5n5xv3h+0mS5S4P/2gydSukuioA5B8HWvGy7AAmBvM2Ww229/2AtzFQw0WWkuiAAAAAElFTkSuQmCC","orcid":"","institution":"Zibo Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Guangming","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2023-12-14 09:14:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3752571/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3752571/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49091799,"identity":"b7025719-3fc2-4101-a041-1767157ffa73","added_by":"auto","created_at":"2024-01-03 01:57:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8486,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment effect\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/a24998ca7ed63b55cc84adb7.png"},{"id":49091795,"identity":"1cd907cc-f750-4c8b-b4cb-5d03ffc3272b","added_by":"auto","created_at":"2024-01-03 01:57:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":9681,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment response and disease control rates\u003c/p\u003e\n\u003cp\u003eNote: # means group B versus group A, P \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003e* means group C versus groups A and B, P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/d7ce4a602feb182f3b7d9bd9.png"},{"id":49093296,"identity":"60f1cd39-6ade-40dd-b164-27eb0f1b0950","added_by":"auto","created_at":"2024-01-03 02:13:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":10112,"visible":true,"origin":"","legend":"\u003cp\u003eContrast of serum AFP\u003c/p\u003e\n\u003cp\u003eThere was not evidently pre-treated distinct in CEA level (P \u0026gt; 0.05). Following treatment, CEA level in group C was lower as against other two (P \u0026lt; 0.05) (Figure 4).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/2e83d50b8918bcd1e2466f47.png"},{"id":49092497,"identity":"e4a0c56e-de71-494e-be78-06d334e8a03b","added_by":"auto","created_at":"2024-01-03 02:05:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":11046,"visible":true,"origin":"","legend":"\u003cp\u003eCEA contrast\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/5766d32a3590858f511a0a3f.png"},{"id":49091794,"identity":"31c54d2b-5ba9-4f29-9a1f-6bc3f894983c","added_by":"auto","created_at":"2024-01-03 01:57:12","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":21218,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival time\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/af87c5260f974a8f3980cd9f.png"},{"id":49091797,"identity":"bf70aaae-256b-49ab-b4f5-3a80ca28fe39","added_by":"auto","created_at":"2024-01-03 01:57:12","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":9227,"visible":true,"origin":"","legend":"\u003cp\u003eContrast of SR\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/87029fe5ff631078b5ce9b72.png"},{"id":49623450,"identity":"09256573-9a8b-41ce-bc9e-6e3579f6e5b1","added_by":"auto","created_at":"2024-01-15 13:22:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":413830,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3752571/v1/93740d74-e3da-4b8c-89aa-f56bd897b29f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Clinical Efficacy of Molecular Targeted Drugs Combined with Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemoembolization Alone for Primary Liver Cancer","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe incidence rate of PLC is very high in in China, accounting for more than 50% of the world. It can occur in people at any age, people at 40\u0026ndash;49 years old is the most, the ratio of men to women is 2\u0026ndash;5:1. About 110,000 people die from liver cancer (LC) in China every year, accounting for 45% of LC deaths in the world [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. PLC is a cancer disease that occurs in the liver and usually originates from epithelial cells. The most common cause of hepatocellular carcinoma is hepatitis B, which hides in liver cells, and many hepatitis B replication will lead to necrosis and proliferation of liver cells, leading to liver cirrhosis, which will further lead to hepatocellular carcinoma [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is generally believed that PLC is related to the following factors: chronic infection, such as viral hepatitis C, viral hepatitis B, liver cirrhosis; external material factors, such as aflatoxin, contaminated water, chemical carcinogens; bad living habits, such as alcoholism, smoking, obesity. Patients with PLC mainly present with persistent upper abdominal pain, accompanied by adverse symptoms such as yellow body surface, loss of appetite, and blue stool [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The most common detection methods for LC are imaging and tumor markers, which can detect liver lesions at an early stage. PLC focuses on prevention, it should be early detection and treatment, but because LC is often found in the late stage, the prognosis is poor. Surgical resection is the preferred treatment to prolong the survival time of LC patients. Radiofrequency ablation, cryotherapy, and microwave therapy can also be selected for LC. Liver transplantation is feasible when small LC with cirrhosis has no vascular tumor thrombus formation and poor liver function presents [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. For patients with advanced LC or unresectable LC, interventional embolization, radiotherapy, systemic chemotherapy, and immunotherapy can be adopted.\u003c/p\u003e \u003cp\u003eTACE is a kind of LC interventional therapy, which refers to a treatment method in which the femoral artery at the root of the thigh of the patient is punctured, a tiny catheter is penetrated, and the catheter is sent to the intrahepatic tumor site under the guidance of the fluoroscopy of the digital subtraction angiography machine. The doctor will inject anti-cancer drugs and embolic agents into the intrahepatic tumor artery through the catheter [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is suitable for patients with advanced PLC who can\u0026rsquo;t be surgically resected, and patients who can be surgically resected but can\u0026rsquo;t or is unwilling to undergo surgery due to old age, severe liver cirrhosis, and other reasons. TACE can not only directly kill tumor cells, but also block tumor blood supply, causing tumor to lose nutrition and die out. Currently, it is the first choice for advanced LC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. TACE has the following advantages: it can treat unresectable advanced hepatocellular carcinoma; The application of interventional therapy before liver tumor resection can reduce the tumor volume, facilitate the second-stage resection, and determine the number of lesions. Local pain, bleeding, and arteriovenous fistula were controlled. Some patients with large tumors have a high risk of postoperative recurrence. Preventive intervention can be performed about 1 month after surgery to kill possible residual active lesions and reduce the recurrence rate. However, TACE alone has limited improvement in survival and poor long-term efficacy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the 21st century, tumor therapy has entered the era of molecular targeted therapy. Molecular targeted therapy refers to the key macromolecules in the process of tumor occurrence and development, including cell signal transduction and other biological pathway targets involved in the process of tumor development, by specifically blocking the signal transduction of tumor cells to control their gene expression and change biological behavior. It also can prevent tumor angiogenesis through resistance, thereby inhibiting the growth and reproduction of tumor cells and exerting anti-tumor effects [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The molecular pathogenesis of tumor cells is complex, which often leads to liver cirrhosis after tissue damage and induces mutations in liver cells at the gene level. The formation, progression, and metastasis of LC are closely correlated with varieties of gene mutations and cell signaling pathways, including the activation of abnormal growth factors and the continuous activation of cell division signaling pathways, anti-apoptosis signaling pathway disorders, and abnormal angiogenesis. The complex molecular pathogenesis of LC suggests that there are multiple potential therapeutic targets, and these targets are the theoretical basis for molecular targeted therapy [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In recent years, some MTD have made some progress in the research and clinical application of LC. (1) Epidermal growth factor receptor inhibitors. It belongs to the transmembrane glycoprotein family with ligand-dependent tyrosine kinase activity, which is overexpressed in kinds of tumors and is often associated with high tumor invasiveness, rapid progression, and poor prognosis. The representative drugs are gefitinib and erlotinib [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. (2) Anti-angiogenic agents. Neovascularization is considered as a key factor for tumor growth, which not only provides nutrients and oxygen for tumors, but also serves as a pathway for tumor cells to enter the systemic circulation and metastasis. The research on the mechanism of tumor angiogenesis and the treatment of tumor by inhibiting angiogenesis has become a research hotspot in tumor treatment, and anti-angiogenic drugs targeting tumor angiogenesis, such as human recombinant endostatin and human recombinant anti-vascular endothelial growth factor monoclonal antibody bevacizumab, have been adopted in clinical practice [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Combination with chemotherapy for advanced malignant tumors has achieved exciting clinical results. (3) Multikinase inhibitors. For example, sorafenib, an oral multikinase inhibitor, can inhibit tumor cell proliferation and tumor angiogenesis, which can play a dual role of anti-angiogenesis and anti-tumor cell proliferation at the same time [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. 78 patients with PLC were grouped and given different treatment methods for observation and follow-up, to explore the clinical efficacy of TACE combined with MTD on PLC patients, and to provide reference for the selection of PLC treatment plans.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Subjects\u003c/h2\u003e \u003cp\u003e78 patients with PLC who were hospitalized in Zibo Central Hospital from February 2020 to November 2021 were enrolled, aged 44\u0026ndash;68 years, including 47 men and 31 women. There were groups A, B, and C, 26 patients in each group. Group A was given with TACE alone, group B with bevacizumab combined with TACE, and group C with sorafenib combined with TACE.\u003c/p\u003e \u003cp\u003eInclusion criteria: clinical diagnosis and staging criteria were consistent with the 2017 edition of the Standard of Diagnosis and Treatment of Primary Liver Cancer; Liver function was classified as Child-Pugh grades A and B (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Tumor node metastasis classification (TNM) stage Ⅱ-Ⅲ (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); Patients without other serious organic diseases; the predicted survival time was 6 months or more.\u003c/p\u003e \u003cp\u003eExclusion criteria: patients who had other malignant tumors; patients with a history of chemotherapy or steroid therapy before surgery. patients unable to complete TACE for various reasons; severe liver dysfunction (liver function grade C), such as severe jaundice, massive ascites or severe cirrhosis, portal hypertension with retrograde blood flow and complete obstruction of the main portal vein, white blood cell\u0026thinsp;\u0026lt;\u0026thinsp;3,000 or systemic extensive metastasis and multiple organ failure; TNM stage was Ⅳ.\u003c/p\u003e \u003cp\u003eWith approval of the ethics committee of Zibo Central Hospital, the patients and their families were informed of all related matters of the experiment, all of them signing the informed consent.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChild-Pugh classification of liver function\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 point\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 points\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 points\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage of encephalopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u0026ndash;4\u003c/p\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscitic fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild/moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere/refractory\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u0026ndash;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u0026ndash;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT extension (seconds)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u0026ndash;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade A: 5\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade B: 7\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade C: 10\u0026ndash;15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eT-primary tumor. TX: primary tumor could not be evaluated; T0: no evidence of primary tumor; T1: single tumor without vascular invasion; T2: single or multiple tumors with vascular invasion, the largest of which was less than 5 cm in diameter; T3: multiple tumors, maximum diameter\u0026thinsp;\u0026gt;\u0026thinsp;5 cm, or tumor involving one portal vein or major branch of hepatic vein; T4: the tumor directly invaded the surrounding organs (except gallbladder), or had penetrated the visceral peritoneum.\u003c/p\u003e \u003cp\u003eN-regional lymph node (RLN). NX: RLN metastasis could not be evaluated; N0: no RLN metastasis; N1: presence of RLN metastasis.\u003c/p\u003e \u003cp\u003eM- distant metastasis (DM). MX: DM could not be evaluated; M0: no DM; M1: There was DM.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTNM staging criteria\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅠ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅡ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅢA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅢB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅢC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAny T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅣ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAny T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAny N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 TACE\u003c/h2\u003e \u003cp\u003eBefore operation: psychological care was given to the patients, and preoperative examinations were completed according to the doctor\u0026rsquo;s advice, such as blood routine, coagulation time, liver, and kidney function, five items of hepatitis B, electrocardiogram, chest X-ray, etc. Before operation, the patients were given short time of breath holding training and adaptive training such as defecation and urination in bed. contrast media, chemotherapeutic agents, embolic agents (commonly used iodized oil and gelatin sponge), anti-allergic drugs, sandbags (patients can also bring their own salt bags), heparin, etc. were prepared. The skin of the patient\u0026rsquo;s bilateral groin and surgical field was routinely prepared, containing the skin of both sides of the perineum and the upper 1/2 of the thigh below the pubic symphysis of the lower abdomen. A light, nutrient-rich diet was taken for 1\u0026ndash;2 d, and fasting and water deprivation were performed for 6 h before surgery. The bladder was emptied, and sedatives and analgesics should be prescribed half an hour before surgery.\u003c/p\u003e \u003cp\u003eProcedure: Puncture was made in the femoral artery 1 cm-3 cm below the midpoint of the inguinal ligament at the point where the pulsation was most obvious. After local anesthesia, the skin was punctured, and a special catheter was inserted into the femoral artery, then into the abdominal aorta, finally into the hepatic artery, and as far as possible into the arterial branches that supply blood to the LC tissue. Embolic agents and chemotherapeutic agents were then infused into the hepatic artery.\u003c/p\u003e \u003cp\u003eFollowing operation, post-embolism syndrome may occur due to the sudden reduction of hepatic arterial blood supply. Corresponding nursing should be done: patients should try to breathe deeply and take oxygen if necessary to improve blood oxygen partial pressure, which was beneficial to the metabolism of liver cells; patients were fasted for 2\u0026ndash;3 d and gradually transitioned to a liquid diet, paying attention to frequent meals and less amount to reduce nausea and vomiting. The puncture site was compressed to stop bleeding, and the hematoma and oozing blood were observed. The pulse, blood pressure, pulse of the dorsal foot artery, and the temperature and color of the skin of the affected limb were observed. If the body temperature exceeds 39℃, it should report to the doctor for treatment. Those with high fever should take cooling measures to avoid body consumption. If patients have different degrees of abdominal pain, it is usually caused by the stimulation of the liver capsule or peritoneum by chemotherapy drugs. The location, nature, and degree of abdominal pain should be closely observed. If the pain is severe, the doctor should be reported for appropriate application of analgesic drugs. Due to the action of high concentration of chemotherapy drugs, it stimulated the gastrointestinal tract and caused nausea and vomiting. The patient was instructed to drink plenty of water to eliminate drug metabolites and bacterial toxins. Some patients reacted strongly and vomited, which should be immediately followed by mouthwash with water. In terms of diet, patients were instructed to eat less irritating food, and those who could eat were encouraged to eat light and easy to digest high-protein and high-vitamin diet. Those who could not eat or had obvious reactions were given infusion support treatment. Treatment was usually repeated every 6\u0026ndash;8 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 MTD therapy\u003c/h2\u003e \u003cp\u003e(1) Patients in group B underwent skin testing for bevacizumab and received a transcatheter arterial infusion of bevacizumab (Avastin, Roche, Basel, Switzerland, approval number: S20120068) at a dose of 4\u0026ndash;6 mg\u0026middot;kg before the first TACE.\u003c/p\u003e \u003cp\u003e(2) Patients in group C received oral administration of sorafenib (Sorafenib Tosylate, Bayer Pharma AG, Leverkusen, Germany, approval number: HJ20160201), 400 mg, twice daily, 3 to 5 d after the initial TACE.\u003c/p\u003e \u003cp\u003eDuring the treatment, the patients were closely observed for ADR, and the severe patients needed to reduce the dose or stop the drug. All the patients were treated for 6 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Follow-up and observation indicators\u003c/h2\u003e \u003cp\u003ePatients in the three groups came to the outpatient clinic every 5\u0026ndash;6 weeks for reexamination, and the follow-up period was 1 year. Patients who died from any cause, lost to follow-up, or reached the follow-up time were regarded as the end of the observation. Observation indicators were as follows.\u003c/p\u003e \u003cp\u003e(1) Clinical efficacy: The clinical efficacy evaluation criteria of tumors are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, and the treatment response rate (CR\u0026thinsp;+\u0026thinsp;PR) and disease control rate (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD) were calculated. Overall survival, defined as the time between the initial diagnosis and death from any cause or loss to follow-up, was examined.\u003c/p\u003e \u003cp\u003e(2) ADR: According to the WHO classification standard for common adverse reactions of anticancer drugs (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), the ADR of patients following treatment was observed and recorded.\u003c/p\u003e \u003cp\u003e(3) Laboratory indicators: the serum levels of AFP and CEA were observed and recorded before and following treatment.\u003c/p\u003e \u003cp\u003e(4) SR: the survival number of patients at 6 months and 12 months following treatment was observed and recorded. SR was computed: (number of survivors in each group/total number in each group) \u0026times;100%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCriteria for efficacy evaluation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEvaluation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Complete response) CR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll the target lesions disappeared.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Partial response) PR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe sum of the maximum diameters of baseline lesions was reduced by at least 30%.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Stable disease) SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe sum of the maximum diameters of baseline lesions decreased or increased but did not reach PR.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Progressive disease) PD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe sum of the maximum diameters of baseline lesions increasing at least 20% or new lesions appearing.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eWHO classification for common toxicity and side effects of anticancer drugs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eⅠ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eⅡ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eⅣ\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95\u0026ndash;109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80\u0026ndash;94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65\u0026ndash;79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༜65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times;109/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0-3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0-2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0-1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༜1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGranulocytes (\u0026times;109/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026ndash;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0-1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u0026ndash;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༜0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (\u0026times;109/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75\u0026ndash;99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u0026ndash;49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༜25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePetechiae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMild bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eObvious bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSevere bleeding\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (\u0026times;N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26\u0026ndash;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༞10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlanine aminotransferase (\u0026times;N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26\u0026ndash;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༞10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlkaline phosphatase (\u0026times;N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26\u0026ndash;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༞10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral cavity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo abnormality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eErythema and pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eErythema, ulcers, able to eat\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUlcers, only liquid diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnable to eat\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTemporary vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVomiting, requiring treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUncontrollable vomiting\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTransient (\u0026lt;\u0026thinsp;2 d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTolerable (\u0026gt;\u0026thinsp;2 d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeeding treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBloody diarrhea\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrea nitrogen (\u0026times;N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26\u0026ndash;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༞10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (\u0026times;N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26\u0026ndash;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༞10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++, +++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNephrotic syndrome\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHematuria under microscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere hematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematuria with blood clots\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUrinary obstruction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDyspnea following activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDifficult to breath at rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eStaying in bed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;38℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u0026ndash;40℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;40℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe fever was accompanied by hypotension\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllergy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEdema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBronchospasm, without treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBronchospasm, needing injection treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAllergic reaction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eErythema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDry desquamation, blisters, and itching\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWet dermatitis, ulcers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExfoliative dermatitis, necrosis, surgery required\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHair\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild hair loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate, patchy hair loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eComplete hair loss, regrowth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHair loss, no regrowth\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecial Site infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSevere infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSevere infection with hypotension\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRhythm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSinus tachycardia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAtrial arrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMultifocal premature ventricular contractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVentricular arrhythmia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbnormal cardiac presences\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTransient cardiac insufficiency needing no therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCardiac insufficiency, effective therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHeart failure, and no response to therapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePericarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePericardial effusion, asymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThere are symptoms, but fluid aspiration is not required\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe pericardial tamponade required fluid aspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCardiac tamponade, requiring surgery\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShort-time sleepiness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThe duration of drowsiness was less than 50% of wakefulness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe duration of drowsiness exceeds 50% of wakefulness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eComa\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral nerves\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSensory abnormalities or tendon reflex decreasing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHeavy paresthesia or mildly weak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnbearable paresthesia or obvious motion impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParalysis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMildly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerately\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFlatulence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbdominal distension and vomiting\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMildly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerately\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDifficult to control\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: N\u0026thinsp;=\u0026thinsp;upper limit of normal value\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eAll experimental data were statistically analyzed by SPSS 24.0 software, measurement data were presented as mean\u0026thinsp;+\u0026thinsp;standard deviation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\overline{\\text{x}}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn;s), count data were statistically inferred by χ2 test, survival follow-up was computed and the curve was drawn by Kaplan-Meier method, and Log-rank test was adopted for contrast. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically meaningful.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Comparison of clinical efficacy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs illustrated in Figures 1 and 2, the effective rate in group A was 15.38%, and the disease control rate was 38.46%. Those in group B were 34.61% and 53.84%, which was superior; and those were higher in group C (50% and 69.23%) (P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Comparison of serum AFP and CEA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePre-treated serum AFP level was not clearly different (P \u0026gt; 0.05), but the serum AFP level was inferior in group C following treatment (P \u0026lt; 0.05) (Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Comparison of ADR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs given in Tables 5 and 6, in terms of ADR, the occurrence probability of group C was generally lower than that of group B. However, in terms of ADR of TACE, there was little difference among the three groups.\u003c/p\u003e\n\u003cp\u003eTable 5 ADR of the two groups\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eClinical manifestations\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eGroup B (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eBleeding\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e3 (11.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eOral cavity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e3 (11.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eNausea and vomiting\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e8 (30.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e6 (23.07%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e9 (34.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eFever\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e14 (53.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e10 (38.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eAllergy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e10 (38.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eConstipation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e15 (57.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e12 (46.15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e11 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e10 (38.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 6 ADR of TACE\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eClinical manifestations\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003eGroup B (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eLocal hematoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.526\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eLocal swelling pain\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e8 (30.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e6 (23.07%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eNausea and vomiting\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e10 (38.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e11 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e10 (38.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e1.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eFever\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e9 (34.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e8 (30.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eAscites\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e1.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eBone marrow suppression\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003ePleural effusion\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003eHepatorenal syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e0.623\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Contrast of survival time\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall survival time was 8.4 months in group A, 10.1 months in group B, and 11.8 months in group C. The overall survival time of group C was longer (P \u0026lt; 0.05) (Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 SR comparison\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e6 months following treatment, the SR had no obvious distinction among the three groups (P \u0026gt; 0.05). 12 months following treatment, the number of survivors was lower in groups A (15/26) and B (19/26) than in group C (22/26). The SR was superior in group C (84.61%) as against other two (57.69%), (73.07%) (P \u0026lt; 0.05) (Figure 6).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe liver is the only organ in the human body with complex structure and function, which is supplied by two sets of blood systems. The portal vein, formed by the confluence of venous blood collected from the spleen, pancreas, and intestine, constitutes 75% of the blood supply of liver and is rich in nutrients but low in oxygen. The proper hepatic artery is a branch of the celiac trunk artery and supplies 25% of the blood to the liver. The hepatic artery is arterial blood, which is rich in oxygen but low in nutrients. The blood from the portal vein and hepatic artery pools into the hepatic vein following passing through the hepatic capillary network. The hepatic vein drains into the inferior vena cava and then returns to the heart [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. During LC, more than 90\u0026ndash;95% of the cancer tissue was supplied by the hepatic artery and less than 10% by the portal vein. Hepatic artery embolization leads to interruption or reduction of blood supply to the tumor, followed by tumor necrosis and shrinkage. TACE is an important treatment method for advanced LC. Generally, the common femoral artery is puncture, and the catheter is passed through the abdominal aorta, celiac trunk, common hepatic artery, and proper hepatic artery to the LC blood supply target artery. Chemoembolization was carried out by injecting the mixture of chemotherapeutic drugs and embolic agents [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. 78 patients with PLC were enrolled and treated with TACE. The clinical treatment and survival time were evaluated. It suggested that after TACE, the patients achieved a certain treatment efficiency and disease control rate, the serum AFP and CEA levels were lower than those before treatment, and the overall survival time was more than 8 months. It indicates that TACE has a relatively obvious therapeutic outcome on PLC. Ando et al. (2021) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] evaluated the efficacy and safety of TACE in patients with advanced hepatocellular carcinoma. It was found that the median survival time of the patients was 11.6 months, which was clearly superior as against other therapies. For patients with advanced hepatocellular carcinoma, TACE can provide deep response and good prognosis. Its advantage is to embolize the blood supply artery of the tumor, resulting in ischemia, hypoxia, and necrosis of the tumor tissue. On the other hand, by increasing the concentration of local tumor drug and prolonging the contact time between drug and tumor tissue, the curative outcome is evidently improved compared with simple perfusion chemotherapy and simple embolization.\u003c/p\u003e \u003cp\u003eHowever, TACE also has some ADR. Following treatment, patients have a series of ADR such as local hematoma, local pain, nausea and vomiting, with no obvious difference. Arslan and Degirmencioglu (2019) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] evaluated ADR in patients with PLC after TACE and found that liver abscess formation was observed in 4 of 163 patients (2.4%) following treatment. Among 313 cases treated with chemoembolization, 4 cases (1.3%) had liver abscess. In addition, biliary-enteric anastomosis was found in two patients, and diabetes mellitus was found in two patients. Doctors should be aware of some complications caused by TACE because of the possibility of worsening the patient\u0026rsquo;s condition or death.\u003c/p\u003e \u003cp\u003eMost LC patients have insidious onset, and early diagnosis is difficult. At diagnosis, LC is locally advanced or has DM, and the surgical resection rate is low. Accurate combination therapy and reasonable sequential therapy can improve the objective response rate, progression-free survival time, and overall survival time of patients. MTD therapy is to use MTD to efficiently and selectively interfere or block cancer cell growth signal transduction pathways, to inhibit the growth of LC cells and reduce the toxic and side effects of drugs on normal tissue cells. Patients in group A were given with TACE alone, patients in group B with bevacizumab combined with TACE, and patients in group C with sorafenib combined with TACE. After comprehensive evaluation, the results revealed that the clinical efficacy, laboratory indexes, survival time, and SR of group C adopting sorafenib were better than those of group A, and were superior than those of group B adopting bevacizumab. Bevacizumab can bind to the free vascular endothelial growth factor in the blood, inhibit the formation of tumor neovascularization, and normalize tumor blood vessels [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Sorafenib is a small molecule receptor tyrosine kinase inhibitor, which belongs to one of the targeted drugs. It can act on tumor cells and tumor blood vessels at the same time, and has a good dual anti-tumor effect. It is often adopted in the adjuvant treatment of advanced LC [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. It was confirmed that sorafenib is valid and safe in advanced LC [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Bevacizumab monotherapy is effective in the treatment of LC, and the results of bevacizumab combined with chemotherapy drugs or other molecular targeted therapy drugs are encouraging. It meant that the treatment of LC has made a breakthrough progress. However, there is still a long way to go for the treatment of PLC because the objective efficacy is still low, the drug price is expensive, and there is no effective method to accurately predict the efficacy or screen the advantageous population.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eBy observation and evaluation, the clinical efficacy of MTD combined with TACE for PLC is better than that of TACE alone. The efficacy, survival time, and SR of sorafenib were better as against bevacizumab. The limitation is that the sample size is not large enough and the source is single. The sample size will be expanded, the effect of combination of multiple MTD should be focused on, and the best usage, dosage, and course of combined therapy should be further clarified to explore the best treatment plan for PLC. In addition, according to the individual differences and genetic polymorphisms of patients, it can find molecular biological markers that can predict the efficacy and toxicity of different MTD, individualized treatment for specific tumor patients to obtain the best treatment outcome with the least economic cost. It provides some reference for the clinical treatment of PLC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figures and tables used to support the findings of this study are included in the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was not supported by any funds.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to show sincere thanks to those techniques who have contributed to this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article does not contain any studies with human participants or animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003eWith approval of the ethics committee of Zibo Central Hospital, the patients and their families were informed of all related matters of the experiment, all of them signing the informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients have given their consent for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXinru Sun and Bojiang Wang, were major contributors in writing the manuscript. Yin Zhang and Baodong Liu, collected the data. BLiping Sun and Guangming Huang realized the scarcity of the two cases, did literature searches, and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eRumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, Laversanne M, McGlynn KA, Soerjomataram I. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022 Dec;77(6):1598-1606. doi: 10.1016/j.jhep.2022.08.021. Epub 2022 Oct 5. PMID: 36208844; PMCID: PMC9670241.\u003c/li\u003e\n \u003cli\u003eZajkowska M, Mroczko B. Chemokines in Primary Liver Cancer. Int J Mol Sci. 2022 Aug 9;23(16):8846. doi: 10.3390/ijms23168846. PMID: 36012108; PMCID: PMC9408270.\u003c/li\u003e\n \u003cli\u003eMD Yang, Chen X L , Hu X Q , et al. Traditional Chinese medicine syndromes distribution in colorectal cancer and its association with Western Medicine Treatment and Clinical Laboratory Indicators. World Journal of Traditional Chinese Medicine, 2019, 5(2):0-0.\u003c/li\u003e\n \u003cli\u003eMejia JC, Pasko J. Primary Liver Cancers: Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma. Surg Clin North Am. 2020 Jun;100(3):535-549. doi: 10.1016/j.suc.2020.02.013. Epub 2020 Apr 16. PMID: 32402299.\u003c/li\u003e\n \u003cli\u003eMacias RIR, Monte MJ, Serrano MA, Gonz\u0026aacute;lez-Santiago JM, Mart\u0026iacute;n-Arribas I, Sim\u0026atilde;o AL, Castro RE, Gonz\u0026aacute;lez-Gallego J, Mauriz JL, Marin JJG. Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics. Aging (Albany NY). 2021 Oct 11;13(19):23416-23434. doi: 10.18632/aging.203620. Epub 2021 Oct 11. PMID: 34633987; PMCID: PMC8544321.\u003c/li\u003e\n \u003cli\u003ePham L, Kyritsi K, Zhou T, Ceci L, Baiocchi L, Kennedy L, Chakraborty S, Glaser S, Francis H, Alpini G, Sato K. The Functional Roles of Immune Cells in Primary Liver Cancer. Am J Pathol. 2022 Jun;192(6):826-836. doi: 10.1016/j.ajpath.2022.02.004. Epub 2022 Mar 23. PMID: 35337836; PMCID: PMC9194651.\u003c/li\u003e\n \u003cli\u003eWege H, Schulze K, von Felden J, Calderaro J, Reig M; rare liver tumors working group of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Rare variants of primary liver cancer: Fibrolamellar, combined, and sarcomatoid hepatocellular carcinomas. Eur J Med Genet. 2021 Nov;64(11):104313. doi: 10.1016/j.ejmg.2021.104313. Epub 2021 Aug 18. PMID: 34418585.\u003c/li\u003e\n \u003cli\u003eUchida-Kobayashi S, Kageyama K, Takemura S, Matsumoto K, Odagiri N, Jogo A, Kotani K, Kozuka R, Motoyama H, Kawamura E, Hagihara A, Yamamoto A, Fujii H, Tanaka S, Enomoto M, Tamori A, Miki Y, Kubo S, Kawada N. Efficacy of rechallenge transcatheter arterial chemoembolization after lenvatinib treatment for advanced hepatocellular carcinoma. JGH Open. 2022 Sep 21;6(11):754-762. doi: 10.1002/jgh3.12819. PMID: 36406645; PMCID: PMC9667401.\u003c/li\u003e\n \u003cli\u003eNouso K, Wakuta A, Kariyama K. Combination therapy of transcatheter arterial chemoembolization with axitinib for the treatment of inoperable hepatocellular carcinoma. Ann Transl Med. 2020 Aug;8(16):1039. doi: 10.21037/atm.2020.03.198. PMID: 32953839; PMCID: PMC7475487.\u003c/li\u003e\n \u003cli\u003eOnishi H, Nouso K, Takaki A, Oyama A, Adachi T, Wada N, Takeuchi Y, Shiraha H, Okada H. History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients. Acta Med Okayama. 2022 Dec;76(6):695-703. doi: 10.18926/AMO/64120. PMID: 36549772.\u003c/li\u003e\n \u003cli\u003eMoriya T, Kawakami N, Wakai Y, Saito H, Saito K. Pulmonary lipiodol embolism following transcatheter arterial chemoembolization. Respirol Case Rep. 2020 Oct 22;8(9):e00678. doi: 10.1002/rcr2.678. PMID: 33117542; PMCID: PMC7581978.\u003c/li\u003e\n \u003cli\u003eLu X, Paliogiannis P, Calvisi DF, Chen X. Role of the Mammalian Target of Rapamycin Pathway in Liver Cancer: From Molecular Genetics to Targeted Therapies. Hepatology. 2021 Jan;73 Suppl 1(Suppl 1):49-61. doi: 10.1002/hep.31310. Epub 2020 Dec 3. PMID: 32394479; PMCID: PMC7655627.\u003c/li\u003e\n \u003cli\u003eHuang A, Garraway LA, Ashworth A, Weber B. Synthetic lethality as an engine for cancer drug target discovery. Nat Rev Drug Discov. 2020 Jan;19(1):23-38. doi: 10.1038/s41573-019-0046-z. Epub 2019 Nov 11. PMID: 31712683.\u003c/li\u003e\n \u003cli\u003eBarbosa R, Acevedo LA, Marmorstein R. The MEK/ERK Network as a Therapeutic Target in Human Cancer. Mol Cancer Res. 2021 Mar;19(3):361-374. doi: 10.1158/1541-7786.MCR-20-0687. Epub 2020 Nov 2. PMID: 33139506; PMCID: PMC7925338.\u003c/li\u003e\n \u003cli\u003eGuterres AN, Villanueva J. Targeting telomerase for cancer therapy. Oncogene. 2020 Sep;39(36):5811-5824. doi: 10.1038/s41388-020-01405-w. Epub 2020 Jul 30. PMID: 32733068; PMCID: PMC7678952.\u003c/li\u003e\n \u003cli\u003eBalon K, Sheriff A, Jack\u0026oacute;w J, Łaczmański Ł. Targeting Cancer with CRISPR/Cas9-Based Therapy. Int J Mol Sci. 2022 Jan 5;23(1):573. doi: 10.3390/ijms23010573. PMID: 35008996; PMCID: PMC8745084.\u003c/li\u003e\n \u003cli\u003ePerez SM, Brinton LT, Kelly KA. Plectin in Cancer: From Biomarker to Therapeutic Target. Cells. 2021 Aug 30;10(9):2246. doi: 10.3390/cells10092246. PMID: 34571895; PMCID: PMC8469460.\u003c/li\u003e\n \u003cli\u003eLev S. Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis. Biochem Soc Trans. 2020 Apr 29;48(2):657-665. doi: 10.1042/BST20191055. PMID: 32311020.\u003c/li\u003e\n \u003cli\u003eNogami N, Barlesi F, Socinski MA, Reck M, Thomas CA, Cappuzzo F, Mok TSK, Finley G, Aerts JG, Orlandi F, Moro-Sibilot D, Jotte RM, Stroyakovskiy D, Villaruz LC, Rodr\u0026iacute;guez-Abreu D, Wan-Teck Lim D, Merritt D, Coleman S, Lee A, Shankar G, Yu W, Bara I, Nishio M. IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2022 Feb;17(2):309-323. doi: 10.1016/j.jtho.2021.09.014. Epub 2021 Oct 7. PMID: 34626838.\u003c/li\u003e\n \u003cli\u003eKelley RK. Atezolizumab plus Bevacizumab - A Landmark in Liver Cancer. N Engl J Med. 2020 May 14;382(20):1953-1955. doi: 10.1056/NEJMe2004851. PMID: 32402168.\u003c/li\u003e\n \u003cli\u003eAntoniotti C, Vetere G, Cremolini C. FOLFOXIRI plus bevacizumab in the treatment of metastatic colorectal cancer patients with unresectable liver metastases. Ann Transl Med. 2022 Sep;10(18):952. doi: 10.21037/atm-22-3656. PMID: 36267710; PMCID: PMC9577793.\u003c/li\u003e\n \u003cli\u003eJaffar Ali D, He C, Xu H, Kumaravel S, Sun B, Zhou Y, Liu R, Xiao Z. Microvesicles mediate sorafenib resistance in liver cancer cells through attenuating p53 and enhancing FOXM1 expression. Life Sci. 2021 Apr 15;271:119149. doi: 10.1016/j.lfs.2021.119149. Epub 2021 Feb 4. PMID: 33549596.\u003c/li\u003e\n \u003cli\u003eGonz\u0026aacute;lez R, Rodr\u0026iacute;guez-Hern\u0026aacute;ndez MA, Negrete M, Ranguelova K, Rossin A, Choya-Foces C, Cruz-Ojeda P, Miranda-Vizuete A, Mart\u0026iacute;nez-Ruiz A, Rius-P\u0026eacute;rez S, Sastre J, B\u0026aacute;rcena JA, Hueber AO, Padilla CA, Muntan\u0026eacute; J. Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer. Redox Biol. 2020 Jul;34:101528. doi: 10.1016/j.redox.2020.101528. Epub 2020 Apr 4. PMID: 32388267; PMCID: PMC7210585.\u003c/li\u003e\n \u003cli\u003eAgopian VG, Yang JD, Zhu Y, You S, Tseng HR. Early detection of primary liver cancer using plasma cell-free DNA fragmentomics: Do all the pieces come together? Hepatology. 2022 Aug;76(2):289-291. doi: 10.1002/hep.32396. Epub 2022 Mar 14. PMID: 35124841.\u003c/li\u003e\n \u003cli\u003eSeager MJ, Jakobs TF, Sharma RA, Bandula S. Combination of ablation and embolization for intermediate-sized liver metastases from colorectal cancer: what can we learn from treating primary liver cancer? Diagn Interv Radiol. 2021 Sep;27(5):677-683. doi: 10.5152/dir.2021.20520. PMID: 34318754; PMCID: PMC8480946.\u003c/li\u003e\n \u003cli\u003eAndo Y, Kawaoka T, Amioka K, Naruto K, Ogawa Y, Yoshikawa Y, Kikukawa C, Kosaka Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Fukuhara T, Mori N, Takaki S, Tsuji K, Nonaka M, Hyogo H, Aisaka Y, Masaki K, Honda Y, Moriya T, Naeshiro N, Takahashi S, Imamura M, Chayama K, Aikata H. Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma. Oncology. 2021;99(8):507-517. doi: 10.1159/000515865. Epub 2021 May 4. PMID: 33946070.\u003c/li\u003e\n \u003cli\u003eArslan M, Degirmencioglu S. Liver abscesses after transcatheter arterial embolization. J Int Med Res. 2019 Mar;47(3):1124-1130. doi: 10.1177/0300060518816875. Epub 2019 Jan 7. PMID: 30614336; PMCID: PMC6421372.\u003c/li\u003e\n \u003cli\u003eMettu NB, Ou FS, Zemla TJ, Halfdanarson TR, Lenz HJ, Breakstone RA, Boland PM, Crysler OV, Wu C, Nixon AB, Bolch E, Niedzwiecki D, Elsing A, Hurwitz HI, Fakih MG, Bekaii-Saab T. Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e2149040. doi: 10.1001/jamanetworkopen.2021.49040. PMID: 35179586; PMCID: PMC8857687.\u003c/li\u003e\n \u003cli\u003eGnocchi D, Castellaneta F, Cesari G, Fiore G, Sabb\u0026agrave; C, Mazzocca A. Treatment of liver cancer cells with ethyl acetate extract of Crithmum maritimum permits reducing sorafenib dose and toxicity maintaining its efficacy. J Pharm Pharmacol. 2021 Sep 7;73(10):1369-1376. doi: 10.1093/jpp/rgab070. PMID: 34014301.\u003c/li\u003e\n \u003cli\u003eRandrian V, Pernot S, Le Malicot K, Catena V, Baumgaertner I, Tacher V, Forestier J, Hautefeuille V, Tabouret-Viaud C, Gagnaire A, Mitry E, Guiu B, Aparicio T, Smith D, Dhomps A, Tasu JP, Perdrisot R, Edeline J, Capron C, Cheze-Le Rest C, Emile JF, Laurent-Puig P, Bejan-Angoulvant T, Sokol H, Lepage C, Taieb J, Tougeron D. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer. Dig Liver Dis. 2022 Jul;54(7):857-863. doi: 10.1016/j.dld.2022.04.024. Epub 2022 May 21. PMID: 35610167.\u003c/li\u003e\n \u003cli\u003eFan B, Zhang Y, Guo S. Imaging Diagnosis of Primary Liver Cancer Using Magnetic Resonance Dilated Weighted Imaging and the Treatment Effect of Sorafenib. Comput Math Methods Med. 2022 Jun 28;2022:8586943. doi: 10.1155/2022/8586943. PMID: 35799672; PMCID: PMC9256338.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PLC, TACE, MTD, sorafenib, bevacizumab","lastPublishedDoi":"10.21203/rs.3.rs-3752571/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3752571/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: it was to explore the therapeutic value of transcatheter arterial chemoembolization (TACE) combined with molecular targeted drugs (MTD) in patients with primary liver cancer (PLC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: 78 patients with PLC hospitalized in Zibo Central Hospital were randomly grouped. Group A was treated with TACE alone, group B with bevacizumab combined with TACE, and group C with sorafenib combined with TACE, 26 cases in each. The patients were followed up for 1 year, and the clinical efficacy, adverse drug reaction (ADR), laboratory indexes, and survival rate (SR) of the three groups were observed and evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The effective rate and disease control rate of group C were 50% and 69.23%, respectively, which were clearly higher than those of groups A (15.38%, 38.46%) and B (34.61%, 53.84%). There was no obvious distinction in serum Alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels among them before treatment. Following treatment, group C (404.37±12.47 ng/mL; 246.52±38.17 ng/mL) were clearly lower than those in groups A (483.74±13.28 ng/mL, 367.28±47.03 ng/mL) and B (450.28±12.19 ng/mL, 291.72±43.69 ng/mL). The incidence of ADR in group C was generally lower than that in groups A and B, without obvious distinction in ADR of TACE among them. The overall survival time was obviously longer in group C (11.8 months) than in groups A (8.4) and B (10.1). Following 6 months of treatment, SR was not evidently different among them. Following 12 months of treatment, the SR was obviously superior in group C (84.61%) as against groups A (57.69%) and B (73.07%) (P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: TACE combined with MTD is superior to TACE alone in the treatment of PLC. The efficacy, survival time, and SR of sorafenib are better than those of bevacizumab.\u003c/p\u003e","manuscriptTitle":"Comparison of Clinical Efficacy of Molecular Targeted Drugs Combined with Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemoembolization Alone for Primary Liver Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 01:57:07","doi":"10.21203/rs.3.rs-3752571/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":"9fe685c7-45c5-495a-b197-5aa00ab46c5a","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-15T13:14:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 01:57:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3752571","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3752571","identity":"rs-3752571","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}