Hepatocellular Carcinoma In China Research Articles

Tislelizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma in China: a cost-effectiveness analysis.

The goal of this study is to compare the cost-effectiveness of tislelizumab and sorafenib as first-line treatment for advanced hepatocellular carcinoma in China. A comprehensive cost-effectiveness analysis was undertaken within the framework of a partitioned survival model to accurately gage the incremental cost-effectiveness ratio (ICER) of tislelizumab compared to sorafenib. The model incorporated relevant clinical data and all survival rates were from RATIONALE-301 trials. The stability of the partitioned survival model was assessed by performing one-way and two-way sensitivity analyses. The total cost incurred for the tislelizumab treatment was $16181.24, whereas the sorafenib was $14306.87. The tislelizumab regimen resulted in a significant increase of 0.18 quality-adjusted life years (QALYs) and an extra cost of $1874.37 as compared to chemotherapy. The ICER was $10413.17 per QALY, which was found to be below the willingness-to-pay (WTP) threshold of $37304.34/QALY. The results of the sensitivity analysis found that no fluctuations in any of the factors affected our results, even when these parameters fluctuated. Tislelizumab appears to be a cost-effective first-line treatment for advanced hepatocellular carcinoma when compared to sorafenib in China. These findings can inform decision-making processes regarding the selection of the most cost-effective treatment option for advanced hepatocellular carcinoma.

Adjuvant TACE plus lenvatinib as compared with TACE alone in patients with hepatocellular carcinoma at high risk of recurrence after surgery: A prospective controlled study.

505 Background: Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer related deaths globally. Radical resection is still the main curative approach for patients with resectable HCC in China. However, the high 5-year postoperative recurrence rate of about 40% to 70% had become the main negative factor affecting the long-term survival benefit. Although transarterial chemoembolisation (TACE) can effectively reduce the recurrence rate and improve disease-free survival (DFS) and overall survival (OS), the outcomes of patients at high risk of recurrence are still not satisfactory. Thus, there is an urgent need for new adjuvant treatment regimen to further improve the survival outcomes. In this study, we compared the efficacy and safety of the lenvatinib plus TACE with TACE alone for postoperative patients with HCC who were at high risk of recurrence. Methods: The factors associated with high risk of recurrence were defined as pathological suggested vascular invasion (including vascular embolus, cholangiocarcinoma embolus and microvascular invasion), suspicious positive surgical margin or surgical margin < 1cm, satellite lesion with cancer, positive lymph nodes, low differentiation and incomplete envelope. Eligible patients were those who had received radical resection for HCC and had risk factors above. Patients were assigned in a 1:1 ratio to receive the combination of lenvatinib and TACE or TACE alone. Results: From September 2019 to May 2023, 119 patients were enrolled in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Sixty received TACE + lenvatinib and 59 received TACE only. The baseline characteristics were similar between two groups. The median duration of follow-up was 22.5 months (rang: 3 to 47) in TACE + lenvatinib group and 23 months (rang: 5 to 48) in TACE group. The 1-year DFS rate was 81.2% (95% CI: 70.8%-93.1%) in lenvatinib + TACE group, which was significantly higher than that of TACE group (58.3% [95% CI: 46.8%-72.7%], p = 0.0087; HR = 0.44 [95% CI: 0.23-0.83]). The median DFS was not reached (95% CI: 28-NR) in lenvatinib + TACE group, and was 20.0 months (95% CI: 12.0-NR) in TACE group. Patients' liver function after treatment with TACE + lenvatinib was comparable to that in the baseline. Conclusions: The preliminary results of this study suggested that adjuvant lenvatinib in combination with TACE can significantly improve DFS compared with TACE alone in patients with HCC at high risk of recurrence after surgery. The toxicity of combined treatment was tolerable and manageable. The follow up is still ongoing to observe the long-term benefit of this treatment regimen.

Multidisciplinary experts consensus on diagnosis and treatment of precancerous lesions of hepatocellular carcinoma (2023 version)

According to the latest statistical data, the incidence and mortality rate of hepatocellular carcinoma in China are still on the rise, posing a major threat to the health of the Chinese population. The occurrence is closely related to the formation of precancerous lesions in the liver. The clinical and basic research on precancerous lesions of hepatocellular carcinoma has developed rapidly, and the concepts and specific techniques for diagnosis and treatment have also undergone new changes and advancements. Therefore, based on the first version in 2020, this consensus has organized multidisciplinary experts to compile and improve a new version by integrating the latest progress in their respective professional fields at home and abroad. It aims to enhance clinicians' understanding of precancerous lesions of hepatocellular carcinoma standardize the pathology, imaging, and molecular diagnostic criteria, broaden early screening methods, formulate scientifically rational treatment plans, and help promote the advancement of diagnosis and treatment strategies and to enhance the overall 5-year survival rate of patients with hepatocellular carcinoma.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Chinese clinical practice guidelines for transarterial chemoembolization of hepatocellular carcinoma (2023 edition)

Transarterial chemoembolization (TACE) is the most commonly used method in the treatment of unresectable hepatocellular carcinoma (HCC), which is a malignancy of hypervascularity originating from hepatocytes. The experts from Chinese College of Interventionalists (CCI) published Chinese Clinical Practice Guidelines for TACE of HCC in 2018 and updated it in 2021. These guidelines have played an important role in standardizing the clinical practice of TACE treatment for HCC in China. With the updated concept, technological progress, and emergence of high-level evidence in accordance with the principles of evidence-based medicine of TACE for HCC, the guidelines were revised and updated again by the experts from CCI. The 2023 edition guidelines not only adopts a more suitable evidence evaluation and recommendation system, but also adds the following contents: TACE in special circumstances, TACE in multidisciplinary diagnosis and treatment of HCC and the whole process management, TACE quality control, hot spots and development direction of TACE, etc. This guideline is based on the latest evidence-based medical evidence and combined with clinical practice, and aims to standardize TACE treatment of HCC in China.

Cost-effectiveness analysis of adding transarterial chemoembolisation to lenvatinib as first-line treatment for advanced hepatocellular carcinoma in China

ObjectiveThe objective of this study was to evaluate the comparative cost-effectiveness of lenvatinib (LEN) plus transarterial chemoembolisation (TACE) (LEN-TACE) and LEN alone to treat advanced hepatocellular carcinoma (HCC) from the...

An observational study of donafenib as adjuvant therapy to prevent hepatocellular carcinoma recurrence after curative surgery.

e16227 Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. Many investigators have suggested adjuvant therapy to prevent HCC recurrence, and several promising outcomes have been reported. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal functions. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: Seventeen patients were enrolled in this study. The median age was 56 years (range, 40–72), 88.2% were males, 82.4% with HBV, 17.6% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 35.3% had tumor diameters ≥5 cm, 29.4% had tumor numbers ≥2, and 29.4% had microvascular invasion. The median follow-up time for the entire patient cohort was 16 months (95% confidence interval [CI], 11.9–20.1), and 5 of 17 patients relapsed, with a recurrence rate of 29.4%. The median RFS was not reached; the 6- and 12-month RFS rates were 88.2% and 70.1%, respectively. Treatment-related adverse events (TRAEs) occurred in 82.4% of the patients, most of which were grades 1–2. Grade 3 TRAEs, including hand-foot skin reaction and rash, were observed in three (16.4%) patients. No grade 4 or 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030 .

Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate-stage hepatocellular carcinoma (HCC): Updated results of a phase II trial.

e16220 Background: The combination of Sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved progression-free survival and overall survival in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate-stage HCC. Methods: Treatment-naïve patients (pts) with potentially resectable intermediate stage (BCLC stage B) HCC were enrolled in this phase II trial (NCT04843943). Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks. Tumor response and resectability were assessed every 6 weeks per RECIST v1.1. Pts with evaluations of partial response (PR) or at least two consecutive stable disease (SD) and eligible for R0 resection were referred for hepatectomy, then continued with sintilimab/bev for at most 12 months. Primary endpoints were event-free survival (EFS) (time from study enrollment to tumor progression, disease recurrence after surgery, or death from any cause) and treatment safety. Secondary endpoints included R0 resection rate, pathologic response, objective response rate (ORR), and disease control rate (DCR). Results: At data cutoff on Feb 7, 2023, 30 pts with BCLC-B stage HCC were enrolled. Of them, 25 pts (83.3%) were up-to-7 criteria out. The median follow-up time was 15.3 months (interquartile range [IQR] 13.8-17.6). ORR and DCR were 26.7% and 90.0% (8 PR and 19 SD). 17 pts (56.7%) met the pre-designated criteria for hepatectomy and received liver resection, including 7 pts were evaluated as PR and 10 as SD before surgery. The median time from initiation of sintilimab/bev to liver resection was 4.3 months (IQR 2.3-5.6). No postoperative mortality was observed. 2 pts had a pathological complete response. Median EFS was 13.8 months (95%CI, 10.3-17.3), and the 6-month and 12-month EFS rates were 76% and 60%, respectively. 3 pts died, and OS data was not mature. Most treatment-related AEs (TRAE) were grade 1-2, and grade 3/4 TRAEs occurred in 7 pts (23.3%). 9 serious adverse events occurred, and 3 of them were treatment associated. Conclusions: For pts with potentially resectable intermediate-stage HCC, sintilimab/bev in combination with liver resection was safe and may improve long-term survival. Clinical trial information: NCT04843943 .

Cost-effectiveness analysis of sorafenib, lenvatinib, atezolizumab plus bevacizumab and sintilimab plus bevacizumab for the treatment of advanced hepatocellular carcinoma in China

Background and ObjectiveHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, especially in China. According to the 2021 Chinese Society of Clinical Oncology guidelines, sorafenib, lenvatinib, atezolizumab combined with bevacizumab, and sintilimab combined with bevacizumab are recommended as first-line treatment options for advanced HCC. This study provides a cost-effectiveness analysis of these treatments from the patient perspective.MethodsA partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.ResultsAll compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.ConclusionsIn this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.

Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine.

Hepatocellular carcinoma (HCC) usually occurs on the basis of chronic liver inflammatory diseases and cirrhosis. The liver microenvironment plays a vital role in the tumor initiation and progression. Exosomes, which are nanometer-sized membrane vesicles are secreted by a number of cell types. Exosomes carry multiple proteins, DNAs and various forms of RNA, and are mediators of cell-cell communication and regulate the tumor microenvironment. In the recent decade, many studies have demonstrated that exosomes are involved in the communication between HCC cells and the stromal cells, including endothelial cells, macrophages, hepatic stellate cells and the immune cells, and serve as a regulator in the tumor proliferation and metastasis, immune evasion and immunotherapy. In addition, exosomes can also be used for the diagnosis and treatment HCC. They can potentially serve as specific biomarkers for early diagnosis and drug delivery vehicles of HCC. Chinese herbal medicine, which is widely used in the prevention and treatment of HCC in China, may regulate the release of exosomes and exosomes-mediated intercellular communication. In this review, we summarized the latest progresses on the role of the exosomes in the initiation, progression and treatment of HCC and the potential value of Traditional Chinese medicine in exosomes-mediated biological behaviors of HCC.

Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis.

The existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC. The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer's perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA. We identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable. Sintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.

Clinical practice guideline on liver transplantation for hepatocellular carcinoma in China (2021 edition).

Clinical practice guideline on liver transplantation for hepatocellular carcinoma in China (2021 edition).

EE85 Cost-Effectiveness Analysis of GAAD Algorithm on the Detection of Early-Stage Hepatocellular Carcinoma in Patients With Chronic Liver Disease in China

When clinically diagnosed as hepatocellular carcinoma in China, 70%-80% of patients are late-stage along with high treatment costs. Several diagnostic strategies are employed but the detection of early-stage HCC is still limited. The emerging GAAD algorithm has demonstrated better performance on early-stage HCC detection, whereas its cost-effectiveness in China is unclear.

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma

BackgroundIn recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC.MethodsA lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model.ResultsCompared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively.ConclusionSintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

711P Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate stage hepatocellular carcinoma (HCC): A phase II trial

The combination treatment using sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved PFS and OS in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate stage HCC.

Ethyl Acetate Fraction of Hedyotis diffusa Willd Induces Apoptosis via JNK/Nur77 Pathway in Hepatocellular Carcinoma Cells.

Background Hepatocellular carcinoma (HCC) is characterized by poor diagnosis and high mortality. Novel and efficient therapeutic agents are urgently needed for the treatment. Hedyotis diffusa Willd (HDW) is used to treat cancers, especially HCC in China. Purpose The study aimed to identify the main anti-HCC extract in HDW and to explore the mechanism of the active extract. Materials and Methods The high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-QTOF-MS) method was used for the simultaneous determination of main compounds in the ethyl acetate fraction of HDW (EHDW). The toxicity test of different HDW fractions was carried out on larvae at 2 day-post-fertilization (dpf) for 72 h. The in vivo anti-HCC effect of different HDW fractions was evaluated on a zebrafish tumor model by immersion administration. The antiproliferative effect of HDW fractions was determined with MTT assay, as well as hematoxylin and eosin (HE) staining assay. Hoechst 33258 staining was used to observe changes in nucleus morphology. Flow cytometry analysis was used to investigate apoptosis induction. Western blot analysis was used to examine apoptosis-related proteins, and key proteins in JNK/Nur77 signaling pathway. SP600125 was served to validate the apoptotic mechanism. Results EHDW showed the strongest tumor cell growth inhibitory effect on zebrafish tumor model. Further study revealed that EHDW induced apoptosis in zebrafish tumor model and in cultured Hep3B cells. Meanwhile, it has been shown that the levels of BCL2-associated X (Bax), cytochrome c (cyto c), cleaved-caspase 3, and poly-ADP-ribose polymerase (PARP) cells were upregulated. In contrast, the level of antiapoptotic B cell lymphoma-2 (Bcl-2) was downregulated in Hep3B cells. Additionally, EHDW activated JNK/Nur77 pathway by increasing the levels of p-JNK(Thr183/Tyr185) and p-Nur77(Ser351). Further study showed that blockage of JNK by SP600125 reversed EHDW-induced JNK/Nur77 pathway and the downstream apoptotic proteins. Conclusion In conclusion, EHDW exerted the anti-HCC effect, which may be attributed to the activation of JNK/Nur77 pathway. This study supported the rationale of HDW as an HCC therapeutic agent.

Evaluation of the health economic impact of initial diagnostic modality selection in patients suspected of having HCC in China and the USA

Aims To compare relative costs associated with the diagnostic pathways for hepatocellular carcinoma (HCC) in the US and China according to the initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to contrast-enhanced multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) and contrast-enhanced ultrasound (CEUS). Materials and methods Decision tree models were developed to simulate the clinical pathway, based on local clinical guidelines, and validated by experts. Input data were derived from the literature (up to 31 December 2020) as well as from interviews with local experts. Results The models showed that compared to alternative initial imaging modalities, EOB-MRI was associated with higher diagnostic accuracy (fewer false-positive and fewer false-negative results). Increasing proportionate use of EOB-MRI resulted in a cost offset per patient (excluding false-negative patients) in both the US (USD 337) and China (CNY 1,443), driven by reductions in scan costs and unnecessary treatment costs. The use of EOB-MRI was also associated with a shorter average waiting time for a final diagnosis and treatment decision for patients compared to MDCT, ECCM-MRI, and CEUS. Conclusion The findings of these models demonstrate that EOB-MRI is the most accurate and rapid imaging modality for the diagnosis of HCC in the US and China, resulting in cost offsets that may benefit the healthcare system.

Expert consensus on transarterial chemoembolization refractoriness and subsequent therapies in hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the fundamental method for the treatment of unresectable hepatocellular carcinoma (HCC). Nevertheless, ineffective repeat TACE may lead to damage on liver function and therefore have negative effect on long-term prognosis of HCC. The concept of "TACE failure/refractoriness" was then proposed to avoid ineffective repeat TACE. Nevertheless, whether the existing definitions of "TACE failure/refractoriness" are applicable to Chinese HCCs remains to be discussed. Combining reported clinical evidence with experts' opinion, the Chinese College of Interventionalists (CCI) TACE Refractoriness Collaboration Group proposed the CCI definition and expert consensus on TACE refractoriness in 2021. The CCI definition and expert consensus aims to make the concept of TACE refractoriness more scientific and objective, so as to better guide clinical practice of TACE for patients with HCC in China.

Abstract 5517: Addition of PD-1 antibody camrelizumab overcame resistance to trastuzumab plus chemotherapy in a HER2-positive, metastatic gallbladder cancer patient

Abstract HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast/gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. Here we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. A 69-year-old male GBC patient was found disease progression in the lung six month after operation, staged IV (T3N0M1). Immunohistochemical (IHC) staining was positive for HER2 (3+) and negative for PD-L1 in both primary and pulmonary lesions. Chemotherapy including S-1 plus gemcitabine, as well as oxaliplatin plus paclitaxel consecutive failed, with a new lesion discovered in the liver. Genomic profiling with a multi-gene NGS panel testing (Onco Panscan࣪, Genetron Health) of the pulmonary lesion showed the presence of TP53 S241Y, ARID2 R273*, EGFR E872K mutations, HER2 amplification (fold change, 8.7), and high tumor mutational burden (TMB 10.33). He was treated with trastuzumab in combination with afatinib and capecitabine. Unfortunately, progressive disease in the lung and brain was observed after two cycles. Due to progression of disease and high TMB of the pulmonary biopsy, also based on the reported activity of PD-1 antibody plus trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer, a triplet regime of camrelizumab, trastuzumab, and oxaliplatin was administered. The lesions of the lung, liver, and brain completely regressed after five cycles. From cycle 8 of maintance regime, an anti-angiogenic agent apatinib was added to treat reactive cutaneous capillary endothelial proliferation (RCCEP), the most common immune-related adverse event (irAE) related to camrelizumab, with complete regression after four months. Currently, the patient remains in remission. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBCs who have developed resistance to chemotherapy and trastuzumab-based targeted therapy. Citation Format: Dong Yan, Xiaomo Li, Li Wang, Yurong Cheng, Si Liu. Addition of PD-1 antibody camrelizumab overcame resistance to trastuzumab plus chemotherapy in a HER2-positive, metastatic gallbladder cancer patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5517.

Clinical practice status of the adjuvant therapy in hepatocellular carcinoma (HCC): A survey of Chinese hepatobiliary surgeons.

e16127 Background: There are different views on the scope of indications for surgical treatment of HCC worldwide. Unlike the Barcelona Clinic Liver Cancer, the European Association for Study of the Liver, and the American Association for the Study of Liver Diseases which recommend surgical resection as the first choice only for early HCC, it is also recommended as the first treatment for selected patients with intermediate or advanced HCC in China. However, in any case, postoperative recurrence is an important issue affecting the long-term survival of HCC patients, and to date, there is no globally recognized treatment algorithm for adjuvant therapy. We performed a survey to understand the patient characteristics and clinical status of hepatobiliary surgeons’ decision aids for adjuvant treatment. Methods: This survey was conducted among senior hepatobiliary surgeons who work at high-volume hospitals in China. Surgeons were asked to fill out an online questionnaire by scanning the QR code. Results: From September to November 2021, 511 surgeons from 55 cities responded. Among them, 70.3% worked in general hospitals, 26.8% in cancer hospitals, and 2.9% in integrative medicine hospitals. The majority of the institutions were tertiary hospitals (91.2 %). When determining whether a patient was suitable or not for adjuvant therapy, surgeons mainly considered tumor factors (chosen by 92.8% and 81.6%) and patient factors (chosen by 80.8% and 75.3%). The analysis showed that the patients whom surgeons considered for adjuvant therapy had one or more of the following characteristics: Tumor factors including China liver cancer (CNLC) stage Ia-IIIb (preoperative), R1 resection, Child-Pugh A or B liver function, well recovery from surgery, presence of ≥1 high-risk recurrence factors (i.e. microvascular invasion, macrovascular tumor thrombus, and hilar lymph node metastasis); Patient factors which were hepatocarcinoma-related medical history (e.g., HBV/HCV) and affordability. Most surgeons used targeted therapy (83.8%, mainly anti-angiogenic multi-kinase inhibitors), TACE (72.8%), or combination therapy (60.3%, mainly targeted drugs combined with immunotherapy or TACE) as adjuvant therapy. When asked to choose the two most related factors impacting treatment compliance, 52.1% chose patients' financial status, and 51.7% considered adverse reactions. Less adverse reactions (71.0% of surgeons), better efficacy (66.7%), and a higher reimbursement ratio (53.3%) were the top 3 unmet need for future adjuvant therapy. Conclusions: This survey presented a patient portrait that Chinese hepatobiliary surgeons considered for adjuvant therapy and the practice patterns in adjuvant therapy for HCC. However, the patient group that can benefit from adjuvant therapy remains to be explored and validated in prospective clinical studies.