Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.     

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma and future treatments for the poor responders

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The most common problem associated with HCC is a high risk of intrahepatic recurrence despite radical treatment, and in many patients, this recurrence has fatal consequences. For patients with advanced-stage HCC according to the Barcelona Clinic Liver Cancer staging system, the multikinase inhibitor sorafenib is the current standard of care. In contrast, hepatic arterial infusion chemotherapy (HAIC) is the recommended treatment in Japan for patients with intermediate-stage or advanced-stage HCC. In this review, we describe the use of HAIC for advanced HCC. Furthermore, we demonstrate an alternative therapy for HCC, the iron chelator deferoxamine, and discuss future therapeutic possibilities.     

Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common cancers worldwide. Surgery, percutaneous ablation and liver transplantation are the only curative treatment modalities for HCC. However, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options for patients with advanced HCC are required. In advanced HCC, according to current international guidelines, sorafenib, a molecular targeted agent, is the standard treatment. However, alternative treatment modalities are required because of the low response rates and unsuitability of molecular agents in real practice. In various treatment modalities, mostly in Asia, hepatic arterial infusion chemotherapy(HAIC) has been applied to advanced HCC with a view to increasing the therapeutic efficacy. HAIC provides direct drug delivery into the tumor feeding vessels and also minimizes systemic toxicities through a greater first-pass effect in the liver. However, the sample sizes of studies on HAIC have been small and large randomized trials are still lacking. In this article, we describe the treatment efficacy of HAIC for advanced stage HCC and discuss future therapeutic possibilities.     

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease. METHODS: Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five hours) for five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC. Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed. RESULTS: Six patients exhibited partial response to this form of HAIC (response rate=33%). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%, 28%, and 7%, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months, respectively. It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors. CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC.     

Effect of a late evening snack using branched‐chain amino acid‐enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

Aim: A late evening snack (LES) is recommended for protein‐energy malnutrition in patients with liver cirrhosis. This study investigated energy metabolism in cirrhotic patients with hepatocellular carcinoma (HCC) and the effects of LES using a branched‐chain amino acid (BCAA)‐enriched nutrient in cirrhotic patients with advanced HCC undergoing hepatic arterial infusion chemotherapy (HAIC). Methods: Energy metabolism was measured using indirect calorimetry for 10 cirrhotic patients without HCC and 36 patients with various stages of HCC. Next, in 23 cirrhotic patients with advanced HCC undergoing HAIC, 13 patients received LES (LES group), and 10 patients received ordinary food (control group). Changes in energy metabolism and glucose tolerance were examined using indirect calorimetry and 75‐g oral glucose tolerance test (OGTT) before and after 1 cycle of treatment. Results: Non‐protein respiratory quotient (npRQ) was significantly lower in patients with advanced HCC than in cirrhotic patients without HCC, or in patients with early‐stage HCC. In cirrhotic patients with advanced HCC undergoing HAIC, npRQ, BCAA/tyrosine ratio (BTR), and prealbumin and ALT levels were significantly improved in the LES group, but not in controls. In addition, area under the concentration curve for glucose (AUC glucose) tended to be improved in the LES group. Conclusions: LES using BCAA‐enriched nutrients appears to improve energy metabolism and glucose tolerance in cirrhotic patients with advanced HCC undergoing HAIC.     

Treatment strategies for hepatocellular carcinoma in Japan

The main methods of treatment for hepatocellular carcinoma (HCC) in Japan are hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Meticulous follow up is then undertaken to check for recurrence, which is treated using repeated RFA or TACE. Hepatic arterial infusion chemotherapy has been introduced as treatment for advanced HCC, and the molecular‐targeted drug sorafenib is also now available. Rigorous medical care using these treatment methods and early diagnosis mean that the prognosis for HCC in Japan is the best in the world. This paper reviews the treatment strategies for HCC in Japan.     

Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.     

A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years]

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.     

Adjuvant hepatic arterial infusion chemotherapy after radical hepatectomy for hepatocellular carcinoma--results of long-term follow-up.

BACKGROUND/AIMS: This clinical study aimed to clarify the effectiveness and indication of adjuvant hepatic arterial infusion chemotherapy (HAIC) that is performed to prevent recurrence after radical hepatectomy for hepatocellular carcinoma (HCC). METHODOLOGY: From January 1986 to December 1992, 135 HCC patients, who tolerated curative hepatic resection in which all of the macroscopic HCC was removed, were included in this study. They were divided into two groups. One group was comprised of 68 patients who received HAIC after radical hepatectomy (HAIC (+) group), and the other group was comprised of 67 patients who received radical hepatectomy alone (HAIC (-) group). In the HAIC (+) group, an emulsion of doxorubicin (30-50 mg) and lipiodol (3-5 ml) was injected from a reservoir every 2 or 3 months for 1 year. RESULTS: The cumulative survival rates in the HAIC (+) group (79.1%, 54.5% and 39.9% at 3, 5, and 7 years after hepatectomy, respectively) were better than those in the HAIC (-) group (69.2%, 38.1% and 26.8%, respectively) (p = 0.086). The disease-free survival rates in the HAIC (+) group (50.8%, 31.7% and 25.6% at 3, 5, and 7 years after hepatectomy, respectively) were significantly better than those in the HAIC (-) group (25.7%, 20.6% and 6.4%, respectively) (p = 0.006). This improvement was evident for 3 years after hepatectomy. The adjuvant HAIC was effective especially in patients with good liver function, whose tumor size ranged between 2.1 cm and 5 cm in diameter, and who received a minor hepatic resection. CONCLUSIONS: Adjuvant HAIC was effective in preventing recurrence after radical hepatectomy for HCC. This treatment is especially indicated for patients with good liver function, whose tumor size ranges between 2.1 cm and 5 cm in diameter, and who have received a minor hepatic resection.     

Study of repeated arterial infusion chemotherapy with a subcutaneously implanted reservoir for advanced hepatocellular carcinoma

We performed repeated arterial infusion chemotherapy (RAIC) in 114 advanced hepatocellular carcinoma (HCC) patients, using a subcutaneous reservoir implanted under ultrasonic guidance. In 60 patients, this was the initial therapy for the primary tumor and the other 54 patients being treated for recurrent tumor. One hundred and seventy-one patients with advanced HCC who had been treated by transcatheter arterial emblization (TAE) or single bolus arterial infusion chemotherapy before RAIC was available served as historical controls. In 97 patients, anticancer agents (4′-epidoxorubicin or acurarubicin) and Lipiodol emulsion were used, and in 17, anticancer agents alone were given. The response rates were 39.2% in the Lipiodol group and 17.6% in the non-Lipiodol group. The dose of Lipiodol and the degree of liver invasion were the most important factors influencing the response rate. The 1-, 2-, and 3-year survival rates were 55.0%, 30.9%, and 21.2%, respectively. The long-termsurvival was compared in relation to Child's classification and the presence or absence of portal vein tumor thrombosis (PVTT). In non-PVTT patients, the results of initial therapy and therapy for recurrence were similar, but recurrent Child's C patients showed a poorer prognosis. In PVTT patients, initial therapy had a better prognosis than treatment for recurrence, but initial Child's C patients had a poor long-termprognosis. During the observation period, no severe complications were encountered, but in Child's C patients, hepatic function sometimes deteriorated. Compared with the results in the 171 controls, RAIC was more useful for advanced HCC as initial therapy, and it was also beneficial for the treatment of recurrence after TAE.     

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Purpose  

Hepatic arterial infusion chemotherapy (HAIC) has often been used as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of HAIC using cisplatin with or without 5-fluorouracil in patients with advanced HCC.     

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: Is the addition of subcutaneous interferon‐α‐2b beneficial?

Aim:  We previously reported the benefits of hepatic arterial infusion chemotherapy (HAIC) using cisplatin (CDDP), 5-fluorouracil (5-FU) [low-dose FP], and leucovorin/isovorin for advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy with HAIC and subcutaneous interferon (IFN)- α-2b in patients with advanced HCC.
Methods:  Of the 48 patients, 31 received low-dose FP with leucovorin/isovorin (HAIC group) and 17 received combination therapy comprising low-dose FP with isovorin and subcutaneous IFN-α-2b (combination group). Prognostic factors were evaluated by univariate and multivariate analyses of the patient and the disease characteristics.
Results:  There were no significant differences in the response rate (patients with complete or partial response/all patients; P  = 0.736) and survival ( P  = 0.399) between both groups. Univariate analysis revealed that IFN therapy was not a significant prognostic factor. Multivariate analysis showed 3 variables, namely, Child–Pugh score ( P  = 0.010), α-fetoprotein level ( P  = 0.0047), and additional therapy ( P  = 0.002), to be significant prognostic factors.
Conclusions:  We considered that combination therapy with HAIC and subcutaneous interferon (IFN)-α-2b was not beneficial for advanced HCC.     

Pathological Complete Remission of Advanced Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis by Hepatic Arterial Infusion Chemotherapy

Cures for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are rare and difficult. We report a case of pathologically confirmed complete remission of HCC induced by hepatic arterial infusion chemotherapy (HAIC). A 45-year-old male patient had a massive HCC in the right lobe of the liver and tumor thrombus in the right and main portal veins. He achieved a partial response after two cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²). After the completion of six cycles he received a curative partial hepatectomy, and histopathology revealed complete necrosis without any viable tumor cell. He was in good health at a 4-month follow-up. These results suggest that this regimen is a promising therapeutic modality for the treatment of advanced HCC with PVTT.     

特异性肿瘤细胞毒T淋巴细胞联合肝动脉插管化疗治疗晚期肝细胞癌前瞻性研究

本文采用对照和随机的方法,前瞻性地研究了特异性肿瘤细胞毒T淋巴细胞(CTLs)加肝动脉化疗(HAIC)联合疗法和单一CTLs疗法及单一HAIC疗法三者在治疗晚期肝细胞癌中的作用。160例诊断为晚期肝细胞癌患者经随机分为A、B和C三组。A组用CTLs加HAIC联合疗法治疗;B组予单一CTLs疗法;C组接受单一HAIC治疗。研究结果提示,联合疗法的总缓解率(完全反应+部分反应)和1、2、3年的生存率均比任何单一治疗组高(P<0.05)。因此,CTLs加HAIC联合疗法可能是治疗晚期肝细胞癌病人有希望的治疗手段。     

Future treatment option for hepatocellular carcinoma: a focus on brivanib

Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is particularly prevalent in the Asia-Pacific region. Guidelines on the treatment of HCC in Japan come from both consensus-based and evidence-based treatment algorithms. However, patients with extensive liver damage and/or more advanced disease (major vascular invasion and/or extrahepatic spread) are currently ineligible for any treatment. Recent knowledge of hepatocarcinogenesis has led to the targeting of new pathways, particularly the angiogenic pathway, with a specific focus on the vascular endothelial growth factor receptor (VEGFR). Apparently the most studied systemic antiangiogenic agent for HCC is sorafenib. An updated version of the aforementioned treatment algorithms recommends sorafenib therapy for advanced HCC patients with Child-Pugh A liver function and extrahepatic spread or major vascular invasion. Moreover, sorafenib is recommended for use in HCC patients who are refractory or intolerant to transarterial chemoembolization (TACE) with well-preserved liver function (Child-Pugh A). However, one of the unresolved issues is anti-VEGF resistance. It is speculated that novel antiangiogenic agents that combine inhibition of other pathways such as fibroblast growth factor receptor signaling in addition to VEGFR signaling might provide a potential mechanism to overcome anti-VEGF resistance in HCC. Brivanib inhibits both VEGF and fibroblast growth factor receptor signaling. To further investigate the benefits of brivanib for advanced HCC, a broad-spectrum, global, phase III development plan, the Brivanib studies in HCC patients at RISK (BRISK) clinical program, has been initiated. Clinical benefits seen with brivanib in the first-line setting, and following the failure of sorafenib therapy, highlight the potential to improve the clinical course of patients with advanced HCC, and this agent may provide a novel therapeutic option for the growing population of patients for whom no other treatment choice exists.     

Hepatic Arterial Infusion Chemotherapy in Combination with Pegylated Interferon-α-2b for Advanced Hepatocellular Carcinoma

Background/Aims: We previously reported that combination therapy comprising hepatic arterial infusion chemotherapy (HAIC) with 3 drugs, namely, cisplatin (CDDP), 5-fluorouracil (5-FU) (low-dose FP) and isovorin and interferon (IFN)-α-2b was not beneficial for patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy comprising HAIC and pegylated interferon (PEG-IFN)-α-2b in advanced HCC patients by comparing our results with previous data. Methodology: From a total of 29 patients, 12 received HAIC and PEGIFN- α-2b (PEG-IFN group) and 17 received HAIC and IFN-α-2b (IFN group). There were no significant differences in clinical characteristics between the 2 groups. Results: The response rate was 33.3% (complete response (CR)=1; partial response (PR)=3) in the PEGIFN group and 47.1% (PR=8) in the IFN group. The 1-, 2- and 3-year cumulative survival rates were 50%, 25% and 8%, respectively, in the PEG-IFN group, whereas they were 53%, 18% and 12%, respectively, in the IFN group. There were no significant differences in the response rate (p=0.251) and survival (p=0.938) between the two groups. Conclusions: We found that combination therapy comprising HAIC using low-dose FP with isovorin and PEG-IFN-α-2b was not beneficial for advanced HCC.     

Therapeutic strategy for postoperative liver metastasis from esophageal squamous cell carcinoma; clinical efficacy of and problem with hepatic arterial infusion chemotherapy

BACKGROUND/AIMS: Despite recent advances in diagnosis and treatment, the prognosis for esophageal squamous cell carcinoma is unsatisfactory. Liver recurrence is frequent in postoperative esophageal squamous cell carcinoma patients, and the prognosis for patients with liver metastasis is poor. This report concerns the therapeutic strategy, especially the efficacy of and the problem with hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma. METHODOLOGY: We performed a retrospective analysis of 8 patients who underwent hepatic arterial infusion between 1993 and 1998. All patients underwent esophagectomy and reconstruction with stomach roll without preoperative chemotherapy and/or radiotherapy. For 6 patients, preceding systemic chemotherapy was performed before hepatic arterial infusion. RESULTS: The overall response rate of hepatic arterial infusion was 50%, and for the responders, hepatic arterial infusion provided a good quality of life. Hepatic arterial infusion was effective for responders to preceding systemic chemotherapy, but ineffective for non-responders. A complete response was seen in 2 patients, and the liver tumors showed no re-growth after the completion of hepatic arterial infusion. Two patients developed stomach roll ulcers and one experienced the catheter thrombosis, but there were no instances of severe toxicity or complications. CONCLUSIONS: For postoperative liver recurrence of esophageal squamous cell carcinoma, hepatic arterial infusion is the favorable therapy in terms of efficacy and low-grade toxicity, but has a risk of causing severe complications. We consider it suitable that when preceding systemic chemotherapy is performed before hepatic arterial infusion, hepatic arterial infusion is performed in responders to preceding systemic chemotherapy, and that hepatic arterial infusion is continued as long as possible.     

Adjuvant hepatic arterial infusion chemotherapy after curative resection for Dukes C colorectal cancer: a pilot study

BACKGROUND/AIMS: The aim of this study was to evaluate the effect and the toxicity of prophylactic adjuvant hepatic arterial infusion chemotherapy (HAIC) on liver metastases and on overall survival of Dukes C colorectal cancer patients. METHODOLOGY: Ninety patients in whom Dukes C colorectal cancer was diagnosed and were treated with curative resection between 1993 and 1997 underwent HAIC. The HAIC regimen consisted of a 24-hour continuous infusion of 1500 mg of 5-fluorouracil, administered once a week for 8 weeks, utilizing a portable infusion drug delivery system to ambulatory patients. Patients to whom 7 g or more of 5-fluorouracil could be given were included in the HAIC group, which resulted in 70 of the 90 patients being in this group. The HAIC group overall survival and liver recurrence rates were compared with those of 62 non-treated cases of Dukes C, which formed the non-HAIC control group. RESULTS: There were no serious toxic effects in this study. Significant differences were seen in the cumulative overall 5-year survival (HAIC group, 84.1%; non-HAIC group, 65.2%; p=0.0369). The cumulative 5-year liver metastasis-free rate was 92.7% in the HAIC group and 78.6% in the non-HAIC group (p=0.0649). In cases of distal lymph node metastasis, a risk factor for liver metastasis, the cumulative 5-year liver metastasis-free rate in the HAIC group (91.7%) was significantly higher than that in the non-HAIC group (58.6%; p=0.0268). CONCLUSIONS: HAIC effectively prevents metachronous liver metastasis, especially in patients with pre-existing distal lymph node metastases, and improves the prognosis of advanced colorectal cancer.     

Evaluation of the “assessment for continuous treatment with hepatic arterial infusion chemotherapy” scoring system in patients with advanced hepatocellular carcinoma

Aim

Sorafenib is the recommended standard of care for advanced hepatocellular carcinoma (HCC) patients. However, hepatic arterial infusion chemotherapy (HAIC) is a treatment option in Asia. We recently developed the assessment for continuous treatment with HAIC (ACTH) score to guide decision‐making for continuous HAIC treatment. The purpose of this study was to validate the utility of the ACTH score in a dedicated cohort.

Methods

One hundred and thirty‐one patients with advanced HCC were enrolled in this study (90 in the training group and 41 in the validation group). The point score (range, 0–3) was calculated as follows: Child–Pugh score before HAIC (A = 0, B = 1), α‐fetoprotein (AFP) response (yes = 0, no = 1), and des‐γ‐carboxy prothrombin (DCP) response (yes = 0, no = 1). The AFP and DCP responses were assessed 2 weeks after HAIC induction; a positive response was defined as a reduction of ≥20% from the baseline.

Results

The DCP response in the validation group was significantly associated with treatment response, and the median survival time (MST) was longer in patients with an ACTH score ≤1 (15.9 months) than in those with a score ≥2 (7.0 months; P = 0.002). Survival in all patients showed significant stratification according to the ACTH score; the MSTs associated with scores of 0, 1, 2, and 3 points were 21.7, 14.4, 9.5, and 3.8 months, respectively.

Conclusion

The ACTH score can aid in the therapeutic assessment and continued treatment planning of HCC patients receiving HAIC.