Transarterial chemoembolization for advanced hepatocellular carcinoma after failure of first-line systemic treatment: a single-center case series

Abstract

Background & aims

To demonstrate the potential benefits of additional transarterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC) after the failure of first-line systemic treatment (ST).

Methods

This retrospective single-center study was conducted between January 2020 and December 2022 on patients with advanced HCC who failed to respond to initial first-line ST. Patients who had previously undergone TACE were excluded. Eligible patients underwent on-demand TACE in addition to ST and were followed until death or until March 2023. The duration of response was recorded. Overall survival (OS) was calculated from the date of failure of first-line ST to the date of death or last follow-up. The primary outcomes were OS and safety, and the secondary outcomes were time to progression (TTP) and objective response rate (ORR).

Results

In total, 18 patients were included; 8 patients had failed to respond to lenvatinib or sorafenib monotherapy, and 10 had failed to respond to a combination therapy. The most common progression pattern was the development of new intrahepatic lesions. Salvage treatment consisted of 16 triple therapies and 2 dual therapies, including TACE. The median duration of follow-up was 9.5 months. The median OS from the start of second-line treatment was 24 months. The median TTP was 3.5 months. The ORR was 55.6%, and disease control was achieved in 94.4% of patients. Treatment-related adverse events were common but acceptable.

Conclusions

Patients with advanced HCC who face significant treatment challenges could potentially benefit from the addition of TACE to second-line ST.

Introduction

Hepatocellular carcinoma (HCC) is a highly prevalent and deadly form of cancer. The majority of patients with HCC present with intermediate- to advanced-stage disease at initial diagnosis; at these stages, individual patients may benefit from transplantation. In such cases, systemic treatment (ST) and transarterial chemoembolization (TACE) are commonly employed as palliative therapies, particularly for Barcelona Clinic Liver Cancer stage B and C (BCLC-B/C) HCC.

ST, which mainly refers to molecular targeted therapeutics (MTTs) and immune checkpoint inhibitors (ICIs), is the first-line treatment option for BCLC-C HCC [1]. Atezolizumab plus bevacizumab, as well as the “STRIDE” regimen, have replaced sorafenib as the preferred first-line options; lenvatinib has also shown comparable survival benefits [2–5]. Despite significant improvements, the median progression-free survival (PFS) remains modest, ranging from 3.78 to 7.4 months, and the median time to progression (TTP) ranges from 2.8 to 8.9 months. Tumor lesions that do not respond or become refractory to ST exist, with an overall response rate (ORR) ranging from 20.1 to 35.4%. In such cases, sequential treatment patterns involving first-line, second-line, and subsequent treatment options have shown potential efficacy. Multiple phase III or Ib/II clinical trials have provided efficacy data for four single agents and one combination therapy approved as second-line strategies, with ongoing studies focusing on ICI-based combination regimens [6–11]. However, only evidence of the treatment migration after sorafenib has been established. The median overall survival (OS) and TTP in these cases have been unsatisfactory (10.6 and 3.2 months, respectively, with regorafenib) compared to placebo. ST-related adverse events (AEs) have also attracted attention. Scientific evidence for any drug to be used after lenvatinib or ICIs is currently lacking.

TACE has been globally adopted as the standard of care for patients with BCLC-B HCC, leading to a median OS of over 30 months, largely owing to its high ORR [1, 12–15]. Promising results have also been observed in a population of patients with BCLC-C predominantly receiving TACE monotherapy [16]. According to the theory of synergistic effects, the addition of TACE to ST has been extensively studied in the first-line setting to improve treatment efficacy. Although this combination appears to offer potential benefits, conflicting results have been reported when compared to ST monotherapy [16–21]. The STAH trial showed that compared to sorafenib alone, sorafenib plus TACE improved TTP, PFS, and disease control rate (DCR) in patients with advanced HCC, but it could not significantly improve the OS [18]. Similar negative results were observed in the SILIUS trial [17]. In contrast, the LAUNCH study suggested that compared to lenvatinib alone, lenvatinib plus TACE could further improve the OS, PFS, and ORR [20]. Similar positive results were reported in a real-world study [19]. However, limited information is available regarding the results of ST plus TACE in the second-line setting. Very few preclinical studies on the combination of regorafenib and TACE have been reported, although prior TACE and other locoregional therapies have been frequently encountered [22, 23].

The present study aimed to demonstrate the potential benefits of incorporating TACE for advanced HCC after the failure of first-line ST.

Materials and methods

Patient selection

This retrospective, single-armed, observational study was conducted in accordance with the Declaration of Helsinki and its later amendments and was approved by the hospital ethics committee. The requirement of obtaining written informed consent from the participants was waived owing to the retrospective design of the study. Consecutive patients with advanced HCC between January 2020 and December 2022 who were treated at a single center were reviewed. Advanced HCC cases encompassed BCLC-C HCC cases, and BCLC-B HCC cases that were deemed primarily unsuitable for TACE [24].

The study had the following patient inclusion criteria: (a) age ≥ 18 years, (b) initial advanced HCC or recurrent advanced HCC after radical therapy, (c) failure of first-line ST, and (d) availability of at least one feasible response evaluation according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria [25]. The exclusion criteria were: (a) prior locoregional therapy, (b) denial or unsuitability to undergo TACE (Child-Pugh class C; Eastern Cooperative Oncology Group score > 1; complete portal vein obstruction; hepatic-portal arteriovenous fistula), (c) systemic chemotherapy, (d) inconsistent radiological data, (e) loss to follow-up, and (f) severe comorbidity.

Failure of first-line ST was defined as disease progression and discontinuation after receiving any therapy based on proven first-line options, except systemic chemotherapy. In the second-line setting, ST plus TACE was defined as any therapy based on proven or emerging first- or second-line options (such as camrelizumab plus apatinib) combined with at least one session of TACE [26].

TACE procedure

Conventional TACE (cTACE) or drug-eluting beads TACE (DEB-TACE) procedures were performed by two interventional radiologists with over 10 years of experience in endovascular procedures using a standardized technique. On-demand TACE was repeated in case of radiologic evidence of viable tumors. However, in cases of contraindications or when the tumors showed refractoriness to further treatment, TACE was discontinued.

ICI and MTT administration

All the approved ICIs and MTTS available in the hospital were used according to the guidelines based on the standard dose and frequency protocols. ICI monotherapy was not allowed in the first-line setting but it was permitted in the second-line setting. Dose adjustments, interruptions, or discontinuations were based on disease response and the occurrence of toxicity. ICIs were typically administrated three days after TACE and a minimum of two full cycles of treatment was required. Oral MTTs were routinely interrupted during the TACE procedure period.

Follow-up and outcome assessments

Each patient was regularly followed up at intervals of 4–8 weeks. The last follow-up date recorded was March 7, 2023. During these visits, each patient underwent contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) every 6–8 weeks. The imaging results were examined by two independent diagnostic radiologists with more than five years of experience in diagnostic imaging. In case of discrepancies in the measurements, a consensus was reached through a discussion between the radiologists. Tumor response was assessed according to the mRECIST.

OS was defined as the time interval from the date of failure of first-line ST to the date of death or last follow-up. TTP was recorded separately from the date of each treatment migration. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Statistical analysis

Data analysis and figure construction were performed using GraphPad Prism 7.0 (GraphPad Software Inc., San Diego, CA, USA) and Origin 2022 (OriginLab, Northampton, MA, USA). Categorical variables were expressed as frequencies and percentages, and continuous variables were reported as median and range. ANOVA was used for comparisons, with P < 0.05 considered statistically significant. Kaplan–Meier analysis was used to demonstrate the PFS and OS.

Results

Baseline patient characteristics

A total of 18 patients were eligible for analysis (Fig. 1). The baseline characteristics of the patients are summarized in Table 1. The median age of the patients was 52.5 (range, 29–80) years, and only one patient was female. Hepatitis B virus (HBV) was detected in 17 (94.4%) patients, and cirrhosis was detected in 13 (72.2%) patients. In total, 12 (66.7%) patients were diagnosed with BCLC-C, with 5 of them showing metastasis in the lungs or lymph nodes. Thirteen HCC cases exceeded the Milan criteria for transplantation. The median duration of follow-up time was 9.5 (range, 2–30) months.

Fig. 1.

Flow chart of patient selection

Table 1.

Patient baseline characteristics before first-line therapy

Characteristics	N(%)
Age, y. Median (range)	52.5 (29–80)
Gender
Male	17(94.4%)
Female	1(5.6%)
Hepatitis B virus
Absent	1(5.6%)
Present	17(94.4%)
Cirrhosis
Absent	5(27.8%)
Present	13(72.2%)
Child-Pugh class
A	17(94.4%)
B	1(5.6%)
ECOG Performance status
0	13(72.2%)
1	5(27.8%)
BCLC Stage
B	6(33.3%)
C	12(66.7%)
Up-to-seven
> 7	13(72.2%)
≤ 7	5(27.8%)
Macroscopic portal vein invasion
Absent	8(44.4%)
Present	10(55.6%)
Extrahepatic spread
Absent	13(72.2%)
Present	5(27.8%)
AFP, ng/ml
≥ 400	5(27.8%)
< 400	8(44.4%)
UK	5(27.8%)
Duration of follow-up	9.5(2–30)

ECOG, Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; AFP, alpha-fetoprotein; UK, unknown

Options and results of first-line treatment

Lenvatinib-based therapies were administrated to a total of eight patients, with five patients receiving monotherapy (Patients 1, 6, 8, 11, and 16) and three patients receiving a combination of lenvatinib with other therapies (Patients 3, 4, and 14). Five patients received ICIs in combination with bevacizumab or its biosimilar (Patients 5, 7, 9, 10, and 18). Sorafenib monotherapy was administered to three patients (Patients 12, 13, and 15), and in one patient, it was combined with atezolizumab (Patient 17). Only one patient received a reported combination of ICI and a tyrosine-kinase inhibitor (Patient 2).

The BCLC stage of two patients (Patients 13 and 14) progressed from stage B to C owing to new extrahepatic spread. The intrahepatic tumor burden aggravated in two patients (Patients 15 and 17). Patient 5 developed portal vein tumor thrombus after treatment. All five described progression patterns were observed, including 10 with new intrahepatic lesions (NIH), 5 with intrahepatic growth (IHG), 2 with new extrahepatic lesions (NEH), 1 with extrahepatic growth (EHG), and 1 with new vascular invasion (nVI; Fig. 2) [27, 28]. The median time from the commencement of first-line ST to progression was 60.5 (range, 28–777) days. Detailed results are shown in Table 2.

Fig. 2.

Colored dot plots of five types of progression patterns upon failure of response to first-line therapies

Table 2.

Selection criteria 1

PatientNO.	First-line treatment	BCLC Stage	Up-to-seven	New-onset PVI or EHS	TTP, d	Progression patterns, IHG/NIH/EHG/NEH/nVI (BCLCp)	Second-line systemic options	TACE sessions	TACE type	Other locoregional therapies
1	Lenvatinib	C	>7	-	31	NIH (p-C1)	Lenvatinib+camrelizumab	3	cTACE	HAIC
2	Camrelizumab+apatinib	C	>7	-	68	NIH (p-C1)	Camrelizumab+apatinib	2	cTACE	-
3	Lenvatinib+sintilimab	C	>7	-	51	NIH (p-C1)	Lenvatinib+camrelizumab	11	cTACE	HAIC
4	Lenvatinib+envafolimab	C	>7	-	75	NIH (p-C1)	Lenvatinib+camrelizumab	6	cTACE	-
5	Atezolizumab+bevacizumab	C	>7	PVI	65	NIH+nVI (p-C2)	Atezolizumab+bevacizumab	5	cTACE	-
6	Lenvatinib	C	>7	-	105	NIH (p-C1)	Lenvatinib	5	cTACE	HAIC; Surgery
7	Sintilimab+bevacizumab biosimilar	C	>7	-	56	IHG (p-C1)	Regorafenib+tislelizumab	3	cTACE	HAIC
8	Lenvatinib	C	>7	-	28	IHG (p-C1)	Lenvatinib+camrelizumab	2	cTACE	HAIC
9	Atezolizumab+bevacizumab	C	>7	-	53	IHG (p-C1)	Atezolizumab+bevacizumab	3	cTACE	HAIC
10	Sintilimab+bevacizumab biosimilar	C	>7	-	44	EHG	Regorafenib+tislelizumab	2	cTACE	HAIC
11	Lenvatinib	B	>7	-	56	NIH (p-B)	Lenvatinib+camrelizumab	6	cTACE	HAIC; Surgery
12	Sorafenib	B	>7	-	32	IHG (p-B)	Camrelizumab	3	cTACE	-
13	Sorafenib	B → C	>7	EHS	777	NEH	Sorafenib+tislelizumab	3	cTACE	-
14	Lenvatinib+tislelizumab	B → C	>7	EHS	54	NEH	Lenvatinib+tislelizumab	3	cTACE	-
15	Sorafenib	B	≤ 7 → >7	-	131	NIH (p-B)	Sorafenib+tislelizumab	5	cTACE	HAIC
16	Lenvatinib	B	>7	-	431	NIH (p-B)	Lenvatinib+camrelizumab	7	cTACE	HAIC
17	Sorafenib+atezolizumab	C	≤ 7 → >7	-	68	NIH (p-C1)	Lenvatinib+atezolizumab	2	cTACE	-
18	Sintilimab+bevacizumab biosimilar	C	>7	-	167	IHG (p-C1)	Sintilimab+bevacizumab biosimilar	2	DEB-TACE	-

Patient NO.	Response Assessment					AFP, ng/ml
	Targeted lesions and new lesions	Non-targeted lesions		New lesions	Overall response	Before first-line therapy	Upon first-line therapy failure	Lowest level after second-line therapy	P
	Intrahepatic lesions	Vascular invasion	Extrahepatic lesions
1	SD	SD	SD	No	SD	UK	72949	39783	0.9018
2	PR	SD	No	No	PR	5600.2	6846	768.3
3	PR	SD	No	No	PR	11356	7486	2052
4	PR	No	No	No	PR	3000	34771	2998
5	PR	SD	No	No	PR	102	121.4	32.71
6	PR	PR	No	No	PR	278	512.9	118.8
7	PR	SD	No	No	PR	18826	5989	3.77
8	SD	SD	No	No	SD	120000	120000	120000
9	SD	SD	No	No	SD	212	140.3	16.54
10	PR	No	SD	No	PR	98.6	36.33	4.02
11	CR	No	No	No	PR	8.65	10.04	9.94
12	PR	No	No	No	PR	UK	92.98	28.9
13	PD	No	SD	No	PD	25.79	29.96	59.63
14	SD	No	SD	No	SD	UK	7.82	4.14
15	SD	No	No	No	SD	UK	363.6	154.1
16	PR	No	No	No	PR	UK	1518	474
17	SD	SD	No	No	SD	15.1	92.42	21.55
18	SD	No	SD	No	SD	63.62	53.2	6.02

Second-line therapies, response assessments

Among the study patients, 16 received triple therapies containing TACE, and 2 patients received dual therapies (Patients 6 and 12). Six patients continued with their original treatment strategies with the addition of TACE; five patients received combinations of ICIs and one patient received monotherapy with lenvatinib. The number of TACE sessions ranged from 2 to 11, with only one patient undergoing two cycles of DEB-TACE (Patient 18). Other locoregional therapies included hepatic artery infusion chemotherapy (HAIC) and palliative resection.

Table 2 presents the best responses according to the mRECIST. Among all patients, 10 (55.6%) patients achieved a partial response, whereas no patient achieved complete response. Thus, the objective response rate was 55.6%. In addition, 7 (38.9%) patients experienced stable disease. The DCR was 94.4%. The specific objective responses and their respective durations for each patient are illustrated in Fig. 3.

Fig. 3.

Duration of objective response in each patient. The black arrow represents ongoing line treatment, the red circle indicates death, and the green hook represents disease-free survival status after radical surgery

Outcomes and AEs

Until the last date of follow-up, eight cases of disease progression and four deaths were observed. The median OS was 24 months, and the median TTP was 21 months (3.5 months among the 8 analyzed patients; Fig. 4).

Fig. 4.

Kaplan–Meier curves show overall survival (OS; A) and time to progression (TTP; B). The number of patients at risk at several time points is listed in parentheses

Postembolization syndrome occurred in 17 (94.4%) patients, and all (100%) patients experienced systemic-related AEs. Among the AEs, grade 1 or 2 events accounted for 72.2%, and grade 3 or 4 AEs accounted for 27.8%. The most common events included transaminase elevation (88.9%), anemia (66.7%) hypothyroidism (44.4%), and hypertension (27.8%; Table 3). No treatment-related deaths were observed.

Table 3.

Adverse events from any cause

Variable	Total	Grade 1 or 2	Grade 3 or 4
PES	17(94.4%)	17(94.4%)	0(0.0%)
ST-related AEs	18(100.0%)	13(72.2%)	5(27.8%)
Transaminase elevation	16(88.9%)	14(77.8%)	2(11.1%)
Thrombocytopenia	2(11.1%)	2(11.1%)	0(0.0%)
Hypoalbuminemia	3(16.7%)	3(16.7%)	0(0.0%)
Hyperbilirubinemia	9(50.0%)	9(50.0%)	0(0.0%)
Leukopenia	1(5.6%)	1(5.6%)	0(0.0%)
Neutropenia	1(5.6%)	1(5.6%)	0(0.0%)
Anemia	12(66.7%)	11(61.1%)	1(5.6%)
Rash or inflammatory dermatitis	1(5.6%)	1(5.6%)	0(0.0%)
Pain	1(5.6%)	0(0.0%)	1(5.6%)
Decreased appetite	1(5.6%)	1(5.6%)	0(0.0%)
Hypothyroidism	8(44.4%)	8(44.4%)	0(0.0%)
Hypertension	5(27.8%)	2(11.1%)	3(16.7%)
HFSR	2(11.1%)	2(11.1%)	0(0.0%)

PES, postembolization syndrome; ST, systemic treatment; AEs, adverse events; HFSR, hand-foot skin reaction

Discussion

Currently, there is growing support from various trials for the combination of TACE and ST as the most dominant treatment option in the first-line setting for unresectable HCC. However, in the second-line setting for advanced HCC, the clinical benefit of this combination has not yet been adequately and systematically evaluated. In this single-center case series study involving 18 patients with HCC, almost all real-life conditions were represented, including various tumor characteristics, first-line treatment protocols, and progression patterns. The combination of TACE and ST revealed promising results, with a 24-month OS observed from the date of failure of first-line ST, along with manageable complications. The TTP was achieved in 8 (44.4%) patients, with a median TTP of 3.5 months. Notably, 55.6% of patients with advanced HCC showed an objective response when treated with regorafenib combined with TACE, and 94.4% of patients achieved disease control. These preliminary outcomes indicate that patients with advanced HCC, even those facing formidable challenges, may potentially benefit from the addition of TACE to ST.

Four types of proven first-line treatment options were administrated to 14 patients in the study. Previous studies have often focused on specific subgroups with a particular treatment regimen, such as atezolizumab plus bevacizumab [29]. In terms of methodology, this study provides a general understanding of second-line therapy, whereas Shao et al. provided a more targeted understanding. The OS for second-line therapy in this study was 24 months, whereas the study by Shao et al. reported an OS of 8 months. However, the results cannot be directly compared owing to the lack of separate results for patients undergoing TACE in the latter study. The decision-making process for treatment selection is influenced by factors such as financial burden, physicians’ preferences, and patients’ choices in real-life practice. In China, physicians generally adhere to guidelines such as the BCLC guidelines or the China National Liver Cancer guidelines for HCC when making treatment-related decisions. As this study is a small case series, conducting a cross-sectional study based on a large database, such as a national platform, may yield more comprehensive epidemiological results.

Advanced HCC exhibits substantial heterogeneity in terms of progression patterns, salvage treatment patterns, and post-progression prognosis. In this study, the most common progression pattern was NIH, followed by IHG, NEH, and EHG/nVI. This finding differs from the results reported by Reig et al. and Talbot et al. [27, 28]. The differences may be attributed to the demographics of the patient cohorts, particularly the prevalence of HBV infection in the current study. In contrast, most of the patients in the other two studies had hepatitis C virus infection or no viral infection. HBV and HCV act on different stages of the carcinogenic process, with HBV initiating the process and HCV promoting its development. Consequently, in the current study, the residual normal liver tissue was more likely to develop NIH lesions in the 18 patients, while IHG was more frequent in the other two studies.

The choice of first-line ST also varies among studies (multiple types of ST vs. sorafenib vs. ICIs). Post-progression prognosis is influenced by specific progression patterns and salvage treatment strategies, as previously mentioned [29]. In this study, TACE combined with ST achieved a post-progression OS of 24 months, which is superior to the OS reported by previous studies and confirms the consolidative effect of subsequent treatment. Although no self-controlled analysis was conducted based on the abovementioned patterns, it is believed that the outcomes of patients in different groups would differ. There have been some suggestions regarding the design of second-line trials and clinical practice, and the addition of TACE has been highlighted as an approach that directly targets intrahepatic solid tumors.

It is worth mentioning that one patient (Patient 11) achieved successful conversion therapy after not achieving a response with lenvatinib monotherapy (Fig. 5). In this case, the tumor was primarily unresectable from a surgical perspective, with risk factors including insufficient future liver remnant and a low chance of achieving R0 resection. While lenvatinib is generally effective, with a good ORR of 24.1%, it seemed ineffective for this patient. However, for some patients, lenvatinib may provide long-term tumor control and improve OS.

Fig. 5.

Successful conversion therapy of Patient 11

Currently, the combination of ICIs and MTTs seems to be a better treatment option compared to single agents alone [30]. The most important considerations in conversion therapy are ORR and mitigation, including tumor progression rate and the time, duration, and depth of remission. TACE and HAIC have shown superiority in this case, as they contribute to a lower tumor progression rate; rapid onset of response, which helps to reduce the exposure time of conversion therapy so as to reduce the incidence of adverse reactions; deeper remission, which is undoubtedly more conducive than subsequent treatment; and longer duration of remission. These factors provide a longer window period for subsequent treatment options. Numerous research studies have provided evidence for the application of locoregional treatment combined with ST in conversion therapy [31, 32].

To date, several clinical trials have been conducted to investigate the use of TACE plus regorafenib with/without ICIs as a second-line therapy for HCC [33]. These studies have demonstrated acceptable results in terms of both safety and efficacy. Similarly, the current study showed promising outcomes with no severe complications. It is important to note that when comparing the results of a single cohort with other studies, differences may be attributed to variations in evaluation criteria, sample sizes, and intervention doses.

This study has several limitations that should be acknowledged. Firstly, it is a retrospective, case series study conducted at a single center, which may limit the generalizability of the findings to other populations. The conclusions drawn from this study must be interpreted with caution and considered as preliminary evidence. Secondly, over half of the patients did not reach the study endpoints, and therefore, the outcomes may be subject to potential bias. Continued follow-up is necessary to obtain a more comprehensive understanding of the long-term outcomes. Thirdly, the TACE procedure itself is heterogeneous. The comparison between cTACE and DEB-TACE remains controversial, and the differences in the efficacy between these two techniques could introduce bias in the results. Moreover, the presence of technical bias in the TACE procedures cannot be ruled out. The lack of a control group, such as a single-agent ST group, and subgroup analysis is another limitation of the study. Considering these limitations, future trials are needed to validate the findings of our study.

In conclusion, this case series study preliminarily demonstrates the promising benefit of the addition of TACE to ST in the second-line setting for advanced HCC involving almost all real-life conditions. The results provide a basis for exploring the efficacy of the combined approach. Future research directions include:1.Multi-center, prospective, randomized controlled trials to further validate the efficacy and safety of the protocol, providing high-level clinical evidence for clinical application.2.Further investigation of TACE protocols (cTACE and DEB-TACE) and different types of systemic treatment regimens to improve efficacy and reduce adverse reactions.3.Research on biomarkers to predict patients who may benefit, which will help personalize treatment and explore the mechanisms underlying the benefits of combination therapy.

Abbreviations

TACE

Transarterial chemoembolization

HCC

Hepatocellular carcinoma

ST

Systemic treatment

OS

Overall survival

TTP

Time to progression

ORR

Objective response rate

BCLC

Barcelona clinic liver cancer

MTTs

Molecular targeted therapeutics

ICIs

Immune checkpoint inhibitors

PFS

Progression-free survival

AEs

Adverse events

DCR

Disease control rate

mRECIST

Modified response evaluation criteria in solid tumors

cTACE

Conventional TACE

DEB-TACE

Drug-eluting beads TACE

CT

Contrast-enhanced computed tomography

MRI

Magnetic resonance imaging

CTCAE

Common terminology criteria for adverse events

HBV

Hepatitis B virus

NIH

New intrahepatic lesion (s)

IHG

Intrahepatic growth

NEH

New extrahepatic lesion (s)

EHG

Extrahepatic growth

nVI

New vascular invasion

HAIC

Hepatic artery infusion chemotherapy

ECOG

Eastern cooperative oncology group

AFP

Alpha-fetoprotein

UK

Unknown

BCLCp

BCLC upon progression

PR

Partial response

SD

Stable disease

PD

Progressive disease

PES

Postembolization syndrome

HFSR

Hand-foot skin reaction

Author contributions

Qingyu Xu and Bin Leng contributed equally to this work. Guowen Yin, Ran You designed the study, performed the experiments, and wrote the manuscript. Bin Leng and Ran You conducted examinations. Chendong Wang, Zeyu Yu and Lingfeng Diao collected the data. Bin Leng and Ran You provided hepatological advice and edited the manuscript. Guowen Yin revised the manuscript for important intellectual content.

Funding

Project for the Development of Young Professional Technical Talent in Jiangsu Cancer Hospital (2017YQL-12).

Data availability

Correspondence and reasonable requests for original dataset should be addressed to the corresponding author.

Declarations

Ethical approval and consent to participate

The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments and was approved by the Ethics Committee of Jiangsu Cancer Hospital. The consents from participants were waived in this retrospective study, which was approved by our ethics committee (KY-2023-025). We declared that patient data was maintained with confidentiality and all the process complies with the requirements of the Ethics Committee of the Jiangsu Cancer Hospital.

Consent for publication

All authors have read the journal’s policies and submitted their manuscripts in accordance with these policies. All authors agree with the content of the article and have submitted it, with prior approval from the department head obtained before submission.

Competing interests

The authors declare no competing interests.