Clinical observation of combined transarterial chemoembolization and targeted therapy in postoperative recurrent colorectal cancer with liver metastasis

Abstract

BACKGROUND

Colorectal cancer (CRC) with liver metastasis remains a significant therapeutic challenge, particularly in cases of postoperative recurrence. While transarterial chemoembolization (TACE) and targeted therapies have shown promise individually, the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.

AIM

To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.

METHODS

This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023. All patients received combined treatment with TACE and targeted therapy: Bevacizumab (40 patients, 53.3%), cetuximab (25 patients, 33.3%), or panitumumab (10 patients, 13.3%). Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria, with overall survival (OS) and progression-free survival as the primary endpoints. Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.

RESULTS

The median OS was 28 months (95% confidence interval: 24-32 months), and the median progression-free survival was 12 months (95% confidence interval: 10-14 months). Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab (median OS, 30 vs 24 months, P = 0.015). The overall response rate was 58.7%, with a disease control rate of 86.7%. Quality of life scores improved significantly across all domains, with greater improvements observed in the bevacizumab group. Treatment-related adverse events were manageable, with grade 3-4 events occurring in 13.3% of the patients and no treatment-related mortality.

CONCLUSION

The combination of TACE with targeted therapy, particularly bevacizumab, has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis. This multimodal approach not only improved survival outcomes but also enhanced the patients’ quality of life, suggesting its potential as a valuable treatment strategy for this challenging condition.

Key Words: Colorectal cancer; Liver metastasis; Transarterial chemoembolization; Targeted therapy; Bevacizumab; Treatment outcomes

Core Tip: This study investigates the combination of transarterial chemoembolization and targeted therapies (bevacizumab, cetuximab, and panitumumab) for the treatment of postoperative recurrent colorectal cancer with liver metastasis. The results indicate that this multimodal approach improved overall survival (28 months) and progression-free survival (12 months), with bevacizumab showing superior outcomes. The treatment is well tolerated, with manageable adverse events, and significantly enhances the patients’ quality of life. This combination therapy has the potential to be an effective and safe strategy for this challenging clinical scenario.

INTRODUCTION

Colorectal cancer (CRC) remains a significant global health burden, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality worldwide[1]. The liver is the most frequent site of metastasis in patients with CRC; liver metastases occur in approximately 50% of cases[2]. The presence of liver metastases significantly worsens the prognosis, reducing the five-year survival rate to less than 15%[3]. Surgical resection of liver metastases offers the best chance for prolonged survival and potential cure; however, a substantial proportion of patients experience postoperative recurrence[4].

In recent years, advancements in interventional oncology have led to the introduction of various locoregional therapies aimed at controlling liver metastases. Transarterial chemoembolization (TACE) is one such technique that delivers chemotherapeutic agents directly to liver tumors while simultaneously obstructing their blood supply, thereby enhancing their cytotoxic effects and minimizing systemic exposure[5]. TACE has been increasingly utilized not only in hepatocellular carcinoma but also in metastatic CRC because of its ability to achieve high local drug concentrations and induce ischemic necrosis in tumor tissues[6]. Despite its potential benefits, the efficacy of TACE alone may be limited by the development of collateral blood flow and survival of residual tumor cells, leading to eventual disease progression[7].

The advent of targeted therapies has revolutionized the treatment of metastatic CRC. Agents targeting the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have shown significant efficacy in controlling tumor growth and progression, particularly when used in combination with chemotherapy[8]. Bevacizumab, a monoclonal antibody against VEGF, inhibits angiogenesis, thereby reducing tumor vascularization and enhancing the effectiveness of chemotherapeutic agents[9]. Similarly, EGFR inhibitors such as cetuximab and panitumumab disrupt critical signaling pathways involved in tumor proliferation and survival, offering another avenue for therapeutic intervention[10]. The integration of targeted therapies with conventional chemotherapy has been associated with improved response rates and survival outcomes in metastatic CRC[11].

The combination of interventional chemotherapy, embolization, and targeted therapy represents a promising approach for the management of recurrent CRC with liver metastasis. This multimodal strategy aims to synergize the localized cytotoxic effects of embolization with the systemic control provided by targeted agents, potentially leading to enhanced therapeutic efficacy and prolonged survival[12]. Recent studies have suggested that combining TACE with targeted therapies may not only improve overall survival (OS) and progression-free survival (PFS), but also reduce the likelihood of further recurrence[13]. However, the optimal combination and sequencing of these therapies remain the subjects of ongoing research, with limited data available specifically addressing their use in postoperative recurrence settings.

Furthermore, the impact of this combined treatment approach on patients’ quality of life is an important consideration, as effective cancer therapies should not only extend survival but also maintain or improve the patient’s functional status and well-being[14]. Although some studies have reported favorable quality of life outcomes with combined locoregional and systemic therapies, comprehensive evaluations for postoperative recurrent CRC with liver metastasis are still lacking[15]. The present study aimed to evaluate the efficacy and safety of combining TACE with targeted therapy in patients with postoperative recurrent CRC accompanied by liver metastasis. These findings are expected to contribute to the optimization of treatment protocols, ultimately enhancing the management and prognosis of patients with this challenging condition.

MATERIALS AND METHODS

Study design and patient population

This observational study was conducted at Bethune International Peace Hospital of PLA between January 2020 and December 2023. The institutional ethics committee approved the study protocol and written informed consent was obtained from all participants. This study was performed in accordance with the guidelines of the Declaration of Helsinki and Good Clinical Practice. Patients with postoperative recurrent CRC with liver metastasis were eligible for enrollment. The inclusion criteria were histologically confirmed colorectal adenocarcinoma, age between 35 and 75 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate organ function, and at least one measurable liver lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The initial staging was performed according to the American Joint Committee on Cancer staging system. The disease-free interval was calculated from the date of primary surgery to the diagnosis of recurrence.

Pretreatment evaluation

All patients underwent comprehensive baseline evaluations, including clinical assessments, laboratory tests, and imaging studies. Molecular profiling was performed to determine KRAS and NRAS mutation status as well as VEGF and EGFR expression levels using standardized immunohistochemistry and genetic testing protocols. Liver metastases were characterized based on number (solitary vs multiple), size, and anatomical location (right lobe, left lobe, or both lobes) using contrast-enhanced computed tomography or magnetic resonance imaging.

Treatment protocol

TACE: Experienced interventional radiologists performed TACE with the patient under local anesthesia with conscious sedation. After selective catheterization of the hepatic artery, angiography was performed to identify tumor-feeding vessels. The chemoembolization protocol included either doxorubicin (50-75 mg/m²) or cisplatin (80-100 mg/m²) mixed with lipiodol. Gelatin sponge particles were used as supplementary embolic materials in selected cases. The procedures were repeated at six-week intervals based on tumor response and patient tolerance.

Targeted therapy: Targeted therapy was administered concurrently with TACE. Three targeted agents were administered: Bevacizumab (40 patients, 53.3%; 5 mg/kg every two weeks), cetuximab (25 patients, 33.3%; initial dose, 400 mg/m², followed by 250 mg/m² weekly), and panitumumab (10 patients, 13.3%; 6 mg/kg every two weeks). Selection of the targeted agent was based on the molecular profiling results, with anti-EGFR therapy restricted to patients with wild-type rat sarcoma viral oncogene homolog (RAS).

Response assessment

Treatment response was evaluated using contrast-enhanced computed tomography or magnetic resonance imaging according to the RECIST 1.1 criteria. Complete response (CR) was defined as the disappearance of all target lesions, partial response (PR) as at least a 30% decrease in the sum of target lesion diameters, progressive disease (PD) as at least a 20% increase, and stable disease (SD) as neither the PR nor PD criteria being met. The overall response rate (ORR) was calculated as the sum of the CR and PR rates, while the disease control rate (DCR) included the CR, PR, and SD rates. The survival outcomes included OS, measured from treatment initiation to death from any cause, and PFS, measured from treatment initiation to disease progression or death.

Safety monitoring

Adverse events were monitored throughout the treatment period and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. TACE-specific complications, including postembolization syndrome, liver dysfunction, and acute kidney injury, were documented. Targeted therapy-related adverse events, particularly hypertension, skin toxicity, and fatigue, were actively monitored. Management strategies included hospitalization when necessary as well as dose modifications or temporary discontinuation of targeted therapy.

Quality of life assessment

Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality of life (EORTC QLQ-C30) questionnaire at baseline and after six months of treatment. The questionnaire assessed the global health status/quality of life, functional scales (physical, role, and social functioning), and symptom scales (fatigue, pain, and nausea/vomiting). Scores were transformed to a 0-100 scale according to the EORTC scoring manual, with higher scores in the functional domains indicating better functioning and higher scores in the symptom domains indicating greater symptom burden.

Statistical analysis

All statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, United States). Continuous variables were expressed as median and range or mean ± SD, while categorical variables were presented as frequencies and percentages. OS was calculated from the date of treatment initiation to death from any cause, and PFS was calculated from treatment initiation to disease progression or death. Survival outcomes were compared between the treatment groups using appropriate statistical tests, with P values reported for between-group comparisons. Multivariate Cox regression analysis was performed to identify independent prognostic factors for OS, with hazard ratios (HR) and 95% confidence intervals (CIs) calculated for significant variables, including the type of targeted therapy, number of liver metastases, and baseline ECOG performance status.

Response rates were calculated according to the RECIST criteria, with the ORR defined as the sum of CR and PR and the DCR using the criteria for ORR with SD. Comparative analyses of the response rates between the bevacizumab and cetuximab/panitumumab groups were performed using appropriate statistical tests. Quality of life scores from the EORTC QLQ-C30 questionnaire were compared between baseline and post-treatment using paired statistical tests, with separate analyses conducted for global health status, functional scales, and symptom scales. For subgroup analyses comparing the bevacizumab and cetuximab/panitumumab groups, changes in quality of life scores were analyzed using appropriate statistical tests. Statistical significance was set at P < 0.05. All tests were two-sided.

RESULTS

Baseline characteristics

A total of 75 patients with postoperative recurrent CRC with liver metastasis were included in this study. The cohort comprised 45 men (60%) and 30 women (40%) with a median age of 58 years (range: 35-75 years). The primary tumor was located in the colon in 40 patients (53.3%) and in the rectum in 35 (46.7%). According to the American Joint Committee on Cancer staging system, 20 patients (26.7%) were initially diagnosed with stage III CRC, whereas 55 (73.3%) presented with stage IV disease at primary diagnosis (Table 1).

Table 1 Baseline characteristics of the study population.

Characteristic	n (%)
Sex
Male	45 (60)
Female	30 (40)
Age, years	58 (35-75)
Primary tumor location
Colon	40 (53.3)
Rectum	35 (46.7)
Initial AJCC stage
Stage III	20 (26.7)
Stage IV	55 (73.3)
Disease-free interval, months	24 (6-60)
Liver metastases
Solitary	30 (40)
Multiple	45 (60)
Number of metastases	3 (1-10)
Average size of metastases, cm	4.5 ± 1.8
Location of metastases
Right lobe	41 (55)
Left lobe	23 (30)
Both lobes	11 (15)
Molecular profiling
KRAS mutation	35 (46.7)
NRAS mutation	15 (20)
Wild-type RAS	25 (33.3)
VEGF overexpression	50 (66.7)
EGFR expression	40 (53.3)
Prior treatments
Systemic chemotherapy	20 (26.7)
Targeted therapy	10 (13.3)

AJCC: American Joint Committee on Cancer; RAS: Rat sarcoma viral oncogene homolog; VEGF: Vascular endothelial growth factor; EGFR: Epidermal growth factor receptor.

Treatment administration

All 75 patients underwent a combination of TACE and targeted therapy. The median number of TACE procedures per patient was three (range: 1-6), administered at six-week intervals. The chemotherapeutic agents used during TACE included doxorubicin in 70 patients (93.3%) and cisplatin in 65 patients (86.7%). Lipiodol was used as the primary embolic agent in 72 patients (96%) and was supplemented with gelatin sponge particles in 60 (80%) (Table 2).

Table 2 Treatment administration details.

Treatment component	n (%)
TACE procedures	3 (1-6)
Chemotherapeutic agents
Doxorubicin	70 (93.3)
Cisplatin	65 (86.7)
Embolic agents
Lipiodol	72 (96)
Gelatin sponge particles	60 (80)
Targeted therapy agents
Bevacizumab	40 (53.3)
Cetuximab	25 (33.3)
Panitumumab	10 (13.3)

TACE: Transarterial chemoembolization.

Survival outcomes

The median OS for the entire cohort was 28 months (95%CI: 24-32 months), and the median PFS was 12 months (95%CI: 10-14 months). Kaplan-Meier survival analysis demonstrated a statistically significant difference in OS between patients receiving bevacizumab and those treated with cetuximab or panitumumab (P = 0.015). The median OS was 30 and 24 months in the bevacizumab and cetuximab/panitumumab groups, respectively. Multivariate Cox regression analysis identified the type of targeted therapy (HR = 0.65, P = 0.019), number of liver metastases (HR = 1.45 per additional metastasis, P = 0.003), and baseline ECOG performance status (HR = 1.30 per unit increase, P = 0.045) as independent prognostic factors for OS (Table 3).

Table 3 Survival outcomes.

Outcome, months	Entire cohort	Bevacizumab group	Cetuximab/panitumumab group	P value
OS	28 (24-32)	30	24	0.015
PFS	12 (10-14)	14	10	0.022

OS: Overall survival; PFS: Progression-free survival.

Response rates

Based on the response RECIST version 1.1, the ORR was 58.7%, with 15 patients (20%) achieving CR and 30 (40.0%) achieving PR. SD was observed in 20 patients (26.7%) and PD occurred in 10 (13.3%). The DCR encompassing CR, PR, and SD was 86.7%. Patients treated with bevacizumab exhibited a higher ORR (62.5%) than those treated with cetuximab/panitumumab (52.0%), although this difference was not statistically significant (P = 0.092). However, DCR was significantly higher in the bevacizumab group (90%) than in the cetuximab/panitumumab group (80%) (P = 0.041) (Table 4).

Table 4 Response rates.

Response category	n (%)
CR	15 (20)
PR	30 (40)
SD	20 (26.7)
PD	10 (13.3)
ORR	45 (58.7)
DCR	65 (86.7)

CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Overall response rate; DCR: Disease control rate.

Adverse events

Treatment-related adverse events of varying severity were documented in all patients. The most common adverse events associated with TACE included post-embolization syndrome (fever, abdominal pain, and nausea) in 60 patients (80%), transient liver dysfunction in 20 (26.7%), and acute kidney injury in 5 (6.7%). Targeted therapy-related adverse events included hypertension in 30 patients (40%), skin rash in 20 (26.7%), and fatigue in 15 (20%).

Severe adverse events (grade 3-4) were observed in 10 patients (13.3%), including hepatic failure in 2 (2.7%), severe hypertension in 3 (4%), and gastrointestinal perforation in 1 (1.3%). Management of adverse events required hospitalization in 8 patients (10.7%) and dose adjustments or temporary discontinuation of targeted therapy in 12 (16%). No treatment-related mortalities were reported during the study period. The incidence of adverse events did not significantly differ between the bevacizumab and cetuximab/panitumumab groups (P = 0.214) (Table 5).

Table 5 Adverse events.

Adverse event	n (%)
TACE-related
Post-embolization syndrome	60 (80)
Transient liver dysfunction	20 (26.7)
Acute kidney injury	5 (6.7)
Targeted therapy-related
Hypertension	30 (40)
Skin rash	20 (26.7)
Fatigue	15 (20)
Severe adverse events (grade 3-4)
Hepatic failure	2 (2.7)
Severe hypertension	3 (4)
Gastrointestinal perforation	1 (1.3)
Management of adverse events
Hospitalization	8 (10.7)
Dose adjustments/discontinuation	12 (16)

TACE: Transarterial chemoembolization.

Quality of life

Quality of life was assessed using the EORTC QLQ-C30 at baseline and after six months of treatment. The global health status/quality of life score improved significantly from a median of 60 (range: 40-80) at baseline to 75 (range: 55-90) after treatment (P < 0.001). Functional scales, including physical, role, and social functioning showed significant improvements, whereas symptom scales for fatigue, pain, and nausea/vomiting were significantly reduced after treatment (Table 6).

Table 6 Quality of life scores, median (range).

Quality of life domain1	Baseline	Post-treatment	P value
Global health status/quality of life	60 (40-80)	75 (55-90)	< 0.001
Physical functioning	55 (30-70)	70 (50-85)	< 0.001
Role functioning	50 (25-65)	68 (45-80)	< 0.001
Social functioning	58 (35-75)	72 (50-88)	< 0.001
Fatigue	65 (40-80)	40 (20-60)	< 0.001
Pain	60 (30-70)	35 (15-50)	< 0.001
Nausea/vomiting	50 (20-60)	25 (10-40)	< 0.001

¹The quality of life domain scores are presented as median (range) based on patient responses. Higher scores in functional domains indicate better functioning, while higher scores in symptom domains indicate greater symptom burden.

Subgroup analysis indicated that patients treated with bevacizumab experienced greater improvements in the global health status and functional scales than those treated with cetuximab/panitumumab (P < 0.05). The bevacizumab group showed a median increase of 20, 15, 18, and 14 points in global health status/quality of life, physical functioning, role functioning, and social functioning, respectively. In contrast, the cetuximab/panitumumab group demonstrated median increases of 10, 8, 9, and 7 points in the respective domains. Additionally, reductions in symptom scores were more pronounced in the bevacizumab cohort, with decreases of 25 points for fatigue, 20 points for pain, and 15 points for nausea/vomiting, compared to 15 points, 10 points, and 10 points, respectively, in the cetuximab/panitumumab group.

DISCUSSION

This study provided a comprehensive evaluation of the combined use of TACE and targeted therapy for the management of postoperative recurrent CRC with liver metastasis. The findings demonstrate that this multimodal therapeutic approach not only prolongs OS and PFS, but also enhances the quality of life of patients, with bevacizumab showing superior efficacy compared to cetuximab or panitumumab. CRC remains a leading cause of cancer-related morbidity and mortality worldwide, and liver metastasis is a common and challenging complication. The liver is the most frequent site of metastasis in patients with CRC and its involvement is associated with poor prognosis and reduced survival rates[16]. Traditional systemic chemotherapy, although effective to some extent, often fails to achieve long-term control of metastatic disease, leading to frequent recurrences and limited survival benefits[17]. TACE works through delivering high concentrations of chemotherapeutic agents directly to the liver tumors while simultaneously blocking their blood supply, thereby inducing tumor necrosis and reducing systemic toxicity[18]. This localized approach not only enhances the cytotoxic effect on tumor cells, but also minimizes the adverse effects typically associated with systemic chemotherapy. In our study, the median OS of 28 months and PFS of 12 months observed in the cohort were notably higher than the survival rates typically reported for patients with metastatic CRC treated with systemic chemotherapy alone, which generally range between 20 and 24 months[19]. The addition of targeted therapies to TACE appears to synergistically enhance the treatment efficacy. Bevacizumab, a monoclonal antibody targeting VEGF, plays a crucial role in inhibiting angiogenesis, thereby restricting tumor growth and metastasis[20]. The superior OS and PFS observed in patients treated with bevacizumab compared to those treated with cetuximab or panitumumab suggest that VEGF inhibition may be more effective in this setting. This could be due to the complementary mechanisms of bevacizumab and TACE, where the anti-angiogenic effects further disrupt the tumor vasculature and enhance the ischemic and cytotoxic effects of TACE[21].

Conversely, EGFR inhibitors, such as cetuximab and panitumumab, target the EGFR pathway, which is involved in tumor cell proliferation and survival. Although these agents have shown efficacy in patients with CRC with wild-type RAS genes, their performance in combination with TACE may not be as robust as that of bevacizumab, as reflected by the lower OS and PFS in our study[22]. This discrepancy could be attributed to differences in patient selection, molecular profiles, and specific interactions between EGFR inhibition and the effects. However, it is important to note that EGFR inhibitors may still offer significant benefits in specific subgroups of patients, particularly those with certain genetic mutations or molecular characteristics[23]. The ORR of 58.7% and DCR of 86.7% observed in this study are encouraging and align with or slightly exceed the results reported in recent literature. Previous studies have demonstrated that combining locoregional therapies with systemic treatments can lead to higher response rates than monotherapies[24]. The higher ORR and DCR in the bevacizumab group further support the notion that VEGF-targeted therapy enhances the efficacy of TACE by more effectively disrupting tumor angiogenesis and facilitating greater tumor necrosis[25]. Improvements in quality of life are a crucial aspect of cancer treatment, as they reflect the patient’s overall well-being and ability to perform daily activities. In our study, significant improvements in global health status/quality of life, physical functioning, role functioning, and social functioning were observed after treatment. Additionally, reductions in the symptom burden, including fatigue, pain, and nausea/vomiting, were noted. These findings are particularly important, as they suggest that the combined therapeutic approach not only extends survival but also enhances the patient’s quality of life, making the treatment more tolerable and beneficial from the patient’s perspective[26].

The safety profile of the combined treatment was acceptable with manageable adverse events and no treatment-related mortality. The incidence of severe adverse events was relatively low at 13.3%, and the types of adverse events observed were consistent with the known side effects of TACE and targeted therapies. This aligns with existing studies that reported manageable toxicity profiles for similar multimodal treatment approaches for metastatic CRC[27]. The comparable incidence of adverse events between the bevacizumab and cetuximab/panitumumab groups suggests that the choice of targeted therapy is primarily based on efficacy, rather than safety concerns.

In this study, multivariate analysis identified the type of targeted therapy, number of liver metastases, and baseline ECOG performance status as independent prognostic factors of OS. The protective effects of bevacizumab highlight its significant role in improving survival outcomes. The positive association between the number of liver metastases and reduced OS emphasizes the importance of the early detection and aggressive management of metastatic disease. Additionally, the baseline ECOG performance status, which reflects the patient’s overall health and functional status, was inversely associated with survival, underscoring the need to maintain optimal patient health to maximize treatment benefits[28].

Comparing our findings with existing literature, our results are consistent with studies that support the use of combined locoregional and systemic therapies in metastatic CRC. For instance, research has shown that TACE can effectively control liver metastases, and when combined with targeted agents such as bevacizumab, can lead to improved survival outcomes[29]. The superior performance of bevacizumab over EGFR inhibitors in our study may reflect the differences in their mechanisms of action and synergistic effects with TACE. However, it is important to acknowledge that some studies have reported benefits with EGFR inhibitors, particularly in patients with specific molecular characteristics such as wild-type RAS genes[30].

Despite these promising results, this study has several limitations that must be considered. First, the retrospective design may have introduced selection bias and limited the generalizability of the findings. Prospective randomized controlled trials are necessary to confirm the efficacy and safety of this combined treatment approach. Second, the sample size, although adequate for initial observations, may not have been sufficient to detect all potential differences between treatment groups, particularly for less common outcomes and adverse events. Additionally, the study was conducted at a single institution, which may affect the applicability of the results to broader populations. Another limitation pertains to the variability in treatment administration, such as differences in the number of TACE procedures and targeted therapy dosing, which could influence the outcomes. Standardizing treatment protocols in future studies would help better assess the true impact of each therapeutic component. Finally, quality of life assessment was based on self-reported measures, which can be subjective and influenced by various factors unrelated to the treatment itself. Incorporating objective measures and longer follow-up periods in future studies will provide more comprehensive insight into the sustained benefits and potential late-onset adverse effects of the combined treatment approach.

CONCLUSION

This clinical observational study demonstrated that the combination of TACE and targeted therapy is an effective and well-tolerated treatment strategy for patients with postoperative recurrent CRC accompanied by liver metastasis. In particular, the integration of TACE with bevacizumab offers significant improvements in OS, PFS, and quality of life compared to EGFR inhibitors.

ACKNOWLEDGEMENTS

The authors would like to express their sincere gratitude to all the medical staff of the Department of Interventional Treatment and the Department of Oncology at the Bethune International Peace Hospital of PLA for their invaluable support and collaboration throughout this study. We are especially grateful to the patients and their families who participated in this study, for their trust and cooperation during the treatment and follow-up process.