Efficacy Analysis of Bronchial Arterial Chemoembolization for Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Objective:

This study aims to comprehensively evaluated the efficacy and safety of bronchial arterial chemoembolization (BACE) in the treatment of advanced nonsmall cell lung cancer (NSCLC) through a meta-analysis of single-group rate, providing evidence-based guidance for clinical treatment.

Materials and Methods:

A systematic search was conducted in PubMed, the Cochrane Library, Embase, and Web of Science databases for relevant studies up to January 15, 2024. Inclusion criteria encompassed single-arm or multi-arm studies of nonrandomized controlled trials, observational studies, and single-arm studies in English language, focusing on NSCLC patients treated with BACE. Data extraction, quality assessment, and statistical analysis were performed following predefined protocols.

Results:

In total, 172 articles were initially retrieved, with 11 studies meeting the inclusion criteria. The included studies comprised 510 patients. Meta-analysis revealed significant heterogeneity among studies for median progression-free survival (PFS), median overall survival (OS), objective response rate, and disease control rate. The combined median PFS was 6.87 months (95% confidence interval [CI] 5.30–8.44), and the combined median OS was 13.68 months (95% CI 10.69–16.67). Subgroup analysis based on intervention measures demonstrated varying efficacy outcomes. Adverse reactions associated with BACE were generally mild, with no reports of grade 3 or higher adverse events.

Conclusion:

BACE emerges as a promising treatment modality for advanced NSCLC, exhibiting favorable efficacy and safety profiles.

Introduction

Lung cancer is the malignant tumor with the highest morbidity and mortality rates in China and worldwide.^1

–5 According to the latest epidemiological data provided by the World Health Organization, there are about 20 million new cancer cases in 2022, while 9.7 million people died from cancer. Lung cancer is the most commonly diagnosed cancer in 2022, accounting for nearly 2.5 million new cases (12.4% of all cancers globally); it remains the foremost cause of cancer mortality, accounting for an estimated 1.8 million deaths, which represents 18.7% of all cancer-related fatalities. This is followed by colorectal cancer at 9.3%, liver cancer at 7.8%, female breast cancer at 6.9%, and gastric cancer at 6.8%.⁶ Nonsmall-cell lung cancer (NSCLC) accounts for 80%−85% of all primary lung cancer,^7,8 specific pathological typing is shown in Figure 1. Due to the lack of public awareness of the clinical manifestations of NSCLC, most of the patients are advanced when diagnosed, resulting in extremely low 5-year survival rates.^3,4,9
–11 Figure 2 presents the detailed mechanisms involved in the development of lung cancer.

FIG. 1.

Proportions of lung cancer subtypes published by WHO in 2022.

FIG. 2.

The development of lung cancer.

The preferred approach for addressing lung cancer involves an anatomical lobectomy, coupled with a dissection of both mediastinal and hilar lymph nodes,^12,13 but since 70% of lung cancer patients are at progressive stage when diagnosed, the surgical resection rate is less than half.^4,10 For those patients who are ineligible for surgery, alternative treatment options must be explored. Currently, the first-line treatment for advanced inoperable NSCLC is mainly platinum-based two-agent chemotherapy combined with radiotherapy and targeted therapy,^14

–19 but patients with NSCLC are often insensitive to systematic chemotherapy and radiotherapy. In addition, adverse reactions such as cancer recurrence, chemotherapy resistance, hematological toxicities, and neuropsychiatric toxicities often lead to patient refusal or intolerance, resulting in generally poor prognoses for the majority of patients.^14,20,21 Hence, it is essential to prioritize effective and less toxic treatments to improve the long-term prognosis for patients with advanced NSCLC. The treatment of locally advanced patients with NSCLC who have failed first-line concurrent chemoradiotherapy is challenging, and searching for effective methods to control localized cancer foci in the lungs is one of the research hotspots in advanced tumor research.

In recent years, interventional therapy has the advantages of minimally invasive, satisfactory efficacy, fewer adverse reactions, quicker postoperative recovery, and saving treatment cost, and has been widely used in the treatment of lung cancer, which significantly increases the survival rate of patients and improves their quality of life. Among them, bronchial arterial chemoembolization (BACE) has become a research hotspot in the field of lung cancer.^22,23 It can not only block the blood supply arteries of the tumor but also directly deliver chemotherapy drugs to the tumor site and release them slowly, thereby prolonging the drug action time, increasing the local drug concentration in the tumor, reducing the blood drug concentration and toxicity throughout the body, and promoting tumor ischemic and necrosis.²⁴ Although BACE has demonstrated some efficacy and safety in the treatment of advanced inoperable NSCLC, the available studies are limited by small sample sizes and a lack of backing from large-scale randomized controlled trials (RCTs). The meta-analysis of single-group rates is a methodological approach that aggregates dichotomous data from uncontrolled cross-sectional studies, which can be clinically used to analyze clinical studies lacking large samples. Based on this, this study used meta-analysis of single-group rate to comprehensively evaluate the efficacy and safety of BACE in the treatment of advanced NSCLC, aiming to furnish a more robust evidence-based foundation for clinical decision-making.

Materials and Method

Selection criteria

Definition of study types

This study included single-arm or multi-arm studies of non-RCT, observational studies (including case-control studies and cohort studies) with single-arm or multi-arm studies, and single-arm studies. The language of the literature was limited to English.

Clarification of study subjects

Patients included in this study must meet the diagnostic criteria for NSCLC (confirmed histopathological subtype through percutaneous needle aspiration biopsy, surgery, or bronchoscopy), regardless of age, gender, race, and region, to ensure the universality and applicability of the study results.

Definition of intervention measures

All patients were treated with bronchial artery chemoembolization alone or in combination with ¹²⁵I seed implantation, microwave ablation (MWA), targeted therapy, or immunotherapy. Specific embolization materials included drug-eluting microspheres, polyvinyl alcohol particles, gelatin sponge particles, and eight spheres microspheres to provide a comprehensive evaluation of the therapeutic efficacy of various embolization materials.

Determination of outcome indicators

The primary outcome indicators of this study included two items: median overall survival (median OS) and median progression-free survival (median PFS). Among them, OS was delineated as the interval extending from the initiation of treatment to the point of the patient’s death, while PFS referred to the duration from the beginning of treatment to either disease progression or death. The secondary outcome indicators of this study included two items: objective response rate (ORR) and disease control rate (DCR). According to the modified Response Evaluation Criteria in Solid Tumors, the treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Among them, ORR was defined as CR+PR and DCR was defined as CR+PR+SD. The selection of these indicators aimed to comprehensively evaluate the effectiveness and safety of the treatment.

Development of exclusion criteria

To ensure the accuracy and reliability of the study, the following exclusion criteria were set: literature not related to the topic, non-English language literature, withdrawn literature, repetitively published literature, reviews, case reports, literature with unavailability of full text, literature with a sample size of fewer than 10 individuals, and literature with unavailable data.

Construction of literature search strategy

This study conducted a computer-based search of four major databases: PubMed, the Cochrane Library, Embase, and Web of Science. During the search process, the subject terms and free words were first determined through querying MESH, and Boolean logic operators were employed for the systematic arrangement and combination of search terms to ensure both comprehensiveness and precision in the search process. The English search terms included “Carcinoma, Non-Small-Cell Lung,” “nonsmall cell lung cancer,” “Chemoembolization, Therapeutic,” “chemoembolization,” “transarterial chemoembolization,” etc. The timeframe for the search was set to January 15, 2024 from the time of construction of each database. The detailed search formula is shown in Supplementary Material 1.

Process of literature screening and data extraction

Two researchers independently carried out the tasks of literature screening and data extraction, subsequently verifying their work through a cross-checking process. In case of any disagreement, a third researcher would be introduced for judgment. The extracted data mainly included key information such as the first author and year of publication, study type, number of patients, disease stage, pathological type, intervention measures, outcome measures, etc. When outcome measures and their 95% confidence intervals (CIs) were not stated within included studies, Kaplan–Meier curves were digitized using the Engauge Digitizer to extract relevant PFS and OS.

Quality evaluation of included literature

To ensure the scientific and rigorous nature of the study, this research used the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool to assess the quality of non-RCTs, observational studies, and other literatures. This tool contains seven evaluation dimensions, including: bias due to confounding, bias in selection of participants into the study, bias due to departures from intended interventions, bias arising from deviations from intended interventions, bias due to missing data, bias in outcome measurement, and bias in the selection of reported results.

Statistical analysis methods

In this study, using Stata MP 17.0, meta-analysis of single-group rate was conducted on both continuous variables and binary variables. The median PFS and median OS were continuous variables, and ORR, DCR, and grade ≥3 adverse events were dichotomous variables. Finally, drawings were made using Adobe Illustrator.

Meta-analysis is primarily used for quantitative pooling analysis of homogeneous data to explore differences among the included independent research data. To achieve this, heterogeneity testing is required for the included research data, including qualitative description using the Q statistic and quantitative description using the I ² statistic, to judge the magnitude of heterogeneity among studies. When I ² is less than 50% and p > 0.1 in the Q test, it suggests that the results of the independent studies are in good agreement, meaning that they have low heterogeneity, and we can use the fixed-effects model for integration analysis when appropriate; otherwise, we employ the random-effects model to conduct the integration analysis.

The results of the meta-analysis of single-group rate are descriptive and do not have a distinction between “positive” or “negative.” In previous meta-analysis of single-group rate, the I ² statistic is often >90%, and the Q statistic is often <0.1. Therefore, regardless of the magnitude of the test statistics, the random-effects model will be used for the analysis in this study, and a forest plot will be used to describe the combined analysis results.

In this study, funnel plots and Egger’s test were employed to assess result bias. Symmetry in the funnel plot or a p-value > 0.05 in Egger’s test indicated a low likelihood of publication bias. In addition, the sensitivity analysis method in this study was the one-by-one exclusion method. It is based on the principle of excluding any one study in turn, and the remaining studies were re-evaluated through meta-analysis to determine if the outcomes of the original meta-analysis were substantially shaped by the impact of specific studies. When the 95% CI after excluding any one study did not include 1 or 0, it represented low sensitivity and robust results. Conversely, it represents high sensitivity and unreliable results.

Results

Overview of literature screening and included studies

After initial screening, we retrieved a total of 172 relevant articles. Through careful reading of titles, abstracts, and full-text contents, 11 articles were ultimately selected for inclusion in this study, covering the treatment outcomes of a total of 510 patients.^{23,25

–34} The detailed literature screening process is illustrated in Figure 3, while Table 1 provides a comprehensive listing of the basic information for the included studies.

FIG. 3.

Flow diagram showing inclusion and exclusions of the studies.

Table 1.

Baseline Characteristics of 11 Studies (Patient and Study Characteristics)

Study	Design	Intervention	Duration (month)	Patients (n)	Tumor stage	Tumor diameter	Median age (years)	Male (%)	Smoking history (%)	ECOG score (≤2)	SCC (%)	Follow-up (month)	Adverse events（grade >2)
Xu et al., 2022³¹	Case-control study	DEB-BACE＋MWA	2017.5–2021.4	28	III/IV	6.2 ± 2.4	66.9 ± 8.9	82.10%	NA	NA	53.60%	21.7 ± 14.1	0
Xu et al., 2022³¹	Case-control study	DEB-BACE	2017.5–2021.4	49	III/IV	6.4 ± 2.8	68.0 ± 10.4	69.40%	NA	NA	53.10%	21.7 ± 14.1	0
Ren et al., 2022²⁹	Single-arm study	DEB-BACE	2018.10–2021.5	31	III/IV	NA	62.3 ± 12.0	65.00%	55.00%	84.00%	65.00%	NA	0
Xu et.al., 2022³¹	Cohort study	DEB-BACE＋PD-1	2016.10–2021.10	27	IIIB-IVB	6.6 ± 2.9	65.3 ± 8.3	81.50%	NA	77.78%	63.00%	28.0 ± 13.2	11.10%
Xu et.al., 2022³¹	Cohort study	DEB-BACE	2016.10–2021.10	57	IIIB-IVB	6.4 ± 2.6	68.2 ± 9.6	75.40%	NA	82.46%	47.40%	28.0 ± 13.2	0
X.-F. LIU et.al., 2021²³	Cohort study	DEB-BACE	2017.1–2018.12	23	IIIB-IV	NA	60.5 ± 10.7	52.20%	60.90%	100.00%	43.50%	NA	0
Liu et al., 2021²³	Single-arm study	DEB-BACE＋Anlotinib	2018.2–2019.8	51	III/IV	NA	61.4 ± 7.5	78.40%	76.50%	100.00%	33.30%	NA	15.70%
Wang et al., 2020²⁵	Case-control study	8 spheres-BACE	2017.4–2017.12	28	IIIA-IIIB	NA	64.4 ± 5.7	71.40%	NA	100.00%	67.90%	12.2 ± 4.3	0
Zhu et al., 2022³⁴	Case-control study	8 spheres-BACE＋Apatinib	2016.11–2020.6	21	IIIB-IV	NA	NA	85.71%	NA	100.00%	100.00%	NA	19.05%
Zhu et al., 2022³⁴	Case-control study	8 spheres-BACE	2016.11–2020.6	26	IIIB-IV	NA	NA	76.93%	NA	100.00%	100.00%	NA	0
Zhao et al., 2023³³	Single-arm study	DEB-BACE	2019.1–2021.1	43	III/IV	4.2 ± 1.3	51.3 ± 12.6	72.09%	NA	NA	83.72%	12.9 ± 6.8	0
Chen et al., 2017²⁶	Case-control study	Gelfoam sponge particles-BACE + 125I	NA	30	III/IV	NA	62.8 ± 4.7	56.67%	NA	NA	36.67%	NA	0
Chen et al., 2017²⁶	Case-control study	Gelfoam sponge particles-BACE	NA	32	III/IV	NA	62.8 ± 4.7	62.50%	NA	NA	53.13%	NA	0
Chen et al., 2020²⁵	Single-arm study	BACE + 125I	2017.9–2019.9	28	IIIA-IIIB	NA	NA	53.57%	NA	100.00%	50.00%	8.1 ± 1.7	0
He et al., 2023²⁷	Case-control study	DEB-BACE	2018.10–2020.1	20	III/IV	5.8 ± 1.9	69.3 ± 8.3	95.00%	NA	NA	100.00%	9.6 ± 4.9	0
He et al., 2023²⁷	Case-control study	PVA-BACE	2018.10–2020.1	16	III/IV	6.2 ± 3.6	64.9 ± 10.8	100.00%	NA	NA	100.00%	9.6 ± 4.9	0

125I, 125I seed implantation; DEB-BACE, drug eluting beads-bronchial arterial chemoembolization; ECOG, Eastern Cooperation Oncology Group; MWA, microwave ablation; PD-1, programmed cell death protein 1 blockade; PVA-BACE, gelatin sponge particles-bronchial arterial chemoembolization; SCC, squamous cell lung cancer.

Results of research quality assessment

Rigorous quality assessments were conducted on the included literature. Among them, the overall risk of bias was low for three single-arm studies and seven non-RCT studies, while the overall risk of bias was moderate for one single-arm study. This demonstrates the reliability and scientific validity of these studies, indicating a high level of research quality. The specific evaluation results are detailed in Table 2.

Table 2.

The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I)

Study	Type of bias							Overall risk of bias
Study	Bias due to confounding	Bias in selection of participants into the study	Bias due to departures from intended interventions	Bias due to deviations from intended interventions	Bias due to missing data	Bias in measurement of outcomes	Bias in selection of the reported result	Overall risk of bias
Sheng Xu et al., 2022³¹	Low	Low	Low	Low	Low	Low	Low	Low
Kewei Ren et al., 2022²⁹	Low	Low	Low	Low	Moderate	Low	Low	Moderate
Sheng Xu et al., 2022³¹	Low	Low	Low	Low	Low	Low	Low	Low
X.-F. Liu et al., 2021²³	Low	Low	Low	Low	Low	Low	Low	Low
Juanfang Liu et al., 2021²⁸	Low	Low	Low	Low	Low	Low	Low	Low
Xiaojun Wang et al., 2020²⁵	Low	Low	Low	Low	Low	Low	Low	Low
Jun Zhu et al., 2022³⁴	Low	Low	Low	Low	Low	Low	Low	Low
Yu Wei Zhao et al., 2023³³	Low	Low	Low	Low	Low	Low	Low	Low
Yaoyong Chen et al., 2017²⁶	Low	Low	Low	Low	Low	Low	Low	Low
Chao Chen et al., 2020²⁵	Low	Low	Low	Low	Low	Low	Low	Low
Guanghui He et al., 2023²⁷	Low	Low	Low	Low	Low	Low	Low	Low

Comprehensive results of meta-analysis

Analysis of median PFS

Eight studies reported in detail the median PFS.^{23,25,27,28,30
–32,34} During the statistical analysis, we detected a significant level of heterogeneity across the studies (p < 0.000, I ² = 95.8%). Consequently, a random-effects model was utilized to perform the meta-analysis. The findings revealed that the pooled median PFS was 6.87 months (median OS = 6.87, 95% CI [5.30, 8.44]). Further subgroup analysis was performed according to various intervention strategies. The results revealed that patients treated exclusively with DEB-BACE had a median PFS of 4.75 months (median PFS = 4.75, 95% CI [2.68, 6.81]); for patients treated with BACE using other embolization materials, the median PFS was 5.97 months (median PFS = 5.97, 95% CI [2.90, 9.04]); and for patients treated with BACE combined with other treatment therapies, the median PFS was 9.36 months (median PFS = 9.36, 95% CI [7.81, 10.91]). Detailed subgroup analysis data are shown in Figure 4.

FIG. 4.

(A) Pooled median overall survival. (B) The subgroup analysis of pooled median overall survival. (C) Pooled median progression-free survival. (D) The subgroup analysis of pooled median progression-free survival.

Analysis of median OS

Nine studies reported in detail the median OS.^{23,26

–33} In the statistical analysis, we detected a significant level of heterogeneity across the studies (p < 0.000, I ² = 93.7%). Thus, a random-effects model was utilized to perform the meta-analysis. The findings revealed that the pooled median OS was 13.68 months (median OS = 13.68, 95% CI [10.69, 16.67]). Further subgroup analysis was performed according to various intervention strategies. The results revealed that patients treated exclusively with DEB-BACE had a median OS of 11.65 months (median OS = 11.65, 95% CI [9.00, 14.30]); for patients treated with BACE using other embolization materials, the median OS was 12.88 months (median OS = 12.88, 95% CI [5.21, 20.55]); and for patients treated with BACE combined with other treatment therapies, the median OS was 17.90 months (median OS = 17.90, 95% CI [12.91, 22.89]). Detailed subgroup analysis data are shown in Figure 4.

Analysis of objective response rate

Ten of these studies were detailed in reporting ORR,^{23,25

–29,31

–34} and we similarly observed statistical heterogeneity (p = 0.000, I ² = 89.227%). Therefore, a random-effects model was utilized to perform the meta-analysis. The subgroup analysis indicated that the ORR for January was 0.386 (ORR = 0.386, 95% CI [0.207, 0.581]), the ORR in February was 0.586 (ORR = 0.586, 95% CI [0.355, 0.800]), and the ORR in March was 0.334 (ORR = 0.334, the 95% CI [0.111, 0.602]); the patient’s June ORR was 0.458 (ORR = 0.458, 95% CI [0.295, 0.625]). Detailed subgroup analysis data are shown in Figure 5.

FIG. 5.

(A) The subgroup analysis of pooled objective response rate. (B) The subgroup analysis of pooled disease control rate.

Analysis of DCR

Ten of these studies reported DCRs in detail,^{23,25

–29,31

–34} and we also observed statistical heterogeneity (p = 0.000, I ² = 92.695%). Therefore, a random-effects model was utilized to perform the meta-analysis. The subgroup analysis indicated that the January DCR for patients was 0.902 (DCR = 0.902, 95% CI [0.706, 1.000]), the February DCR for patients was 0.886 (DCR = 0.886, 95% CI [0.732, 0.983]), and the March DCR for patients was 0.769 (DCR = 0.769, the 95% CI [0. 563, 0.926]); and the June DCR for patients was 0.732 (ORR = 0.732, 95% CI [0.575, 0.866]). Detailed subgroup analysis data are shown in Figure 5.

Analysis of incidence of adverse reactions

All included studies provided detailed accounts of the occurrence of adverse reactions.^{23,25

–34} Among them, only three articles mentioned adverse reactions exceeding grade 3, and these adverse reactions were all due to the use of apatinib or immune checkpoint inhibitors. As for BACE, the most common adverse reactions included nausea, vomiting, pain, fever, abnormal liver function, and bone marrow suppression. It is worth mentioning that no reports of grade 3 or higher adverse reactions caused by BACE were found in all studies.

Results of sensitivity analysis

To assess the stability of the meta-analysis results, we performed a sensitivity analysis using median PFS and median OS as indicators. After excluding the literature one by one, the obtained results were not significantly affected, which indicated that our findings were highly stable. The detailed results of the sensitivity analysis are presented in Figure 6.

FIG. 6.

(A) The result of sensitivity analysis of overall survival. (B) The result of sensitivity analysis of progression-free survival. (C) The result of publication bias of overall survival. (D) The result of publication bias of progression-free survival.

Discussion on publication bias

To explore the potential publication bias in this study, we conducted a publication bias analysis using median PFS and median OS as indicators. The results showed that the funnel plot was asymmetrical, which usually suggests the existence of heterogeneity in the studies. However, further Egger test results revealed the p-values of 0.641 for median PFS and 0.366 for median OS, both exceeding 0.05. This suggests a low likelihood of publication bias in the study. The specific results of the publication bias analysis are detailed in Figure 6.

Discussion

As of 2022, lung cancer will remain the leading malignant tumor in China in terms of morbidity and mortality.^10,35 Due to the atypical symptoms of early-stage lung cancer, most patients are already in advanced stages upon diagnosis, and the success rate of radical surgery is low.¹¹ The conventional treatment for advanced lung cancer is combined radiotherapy; however, most patients have poor prognosis due to tumor recurrence, chemotherapy resistance, bone marrow suppression, and other adverse effects.¹⁴ In recent years, BACE has become a popular choice for the treatment of advanced lung cancer, especially for patients with advanced NSCLC who have relapsed, refractory, or refused chemotherapy after standard treatment.^{29,36

–41}

The mechanism of BACE is that it utilizes bolus microspheres to slowly and steadily release chemotherapeutic drugs, ensuring that high drug concentrations are maintained inside the tumor, typically 2–6 times higher than those administered intravenously.^42,43 In addition, these drugs are able to re-enter the tumor through the blood circulation to administer secondary chemotherapy.²⁵ At the same time, given that the main blood supply artery for lung cancer is the bronchial artery,^44,45 embolic microspheres, after embolizing this artery, can slow down the blood flow and reduce the inflow of chemotherapeutic drugs into the circulation and nontarget tissues, thus prolonging the residence time and duration of action of the drugs in the vascular bed of the tumor,⁴⁶ further inhibiting the transmembrane ion pumps and enhancing the uptake of chemotherapeutic drugs by tumors,⁴⁷ thus enhancing the chemotherapeutic effect of chemotherapy while embolizing the arteries of the tumor’s blood supply.^42,46
–48

The study by Bie et al. showed that the application of drug-loaded microspheres for the treatment of NSCLC demonstrated some efficacy with median PFS of 8.0 months and median OS of 16.5 months.³⁶ This study showed that BACE treatment for patients with advanced NSCLC had a significant prolongation of median OS and median PFS. Further subgroup analysis revealed that the median OS and median PFS of BACE combination therapy were significantly longer compared with BACE monotherapy, which may be attributed to the following factors: on the one hand, the embolization of the tumor blood supply artery by BACE may cause local ischemia and hypoxia of the tumor, but it may also promote the formation of new blood vessels in the peripheral tissues of the tumor, which may lead to the recurrence of the tumor; on the other hand, the targeted therapy combination selectively binds to the ATP site on intracellular vascular endothelial growth factor receptor-2, which subsequently inhibits tumor neovascularization.⁴⁹ And then, MWA or ¹²⁵I seed implantation can directly inactivate most of the tumor tissues,³¹ and BACE continuously releases loaded chemotherapeutic drugs through microspheres and embolizes the tumor-supplying arteries to reduce collateral circulation and enhance the synergistic anticancer effect on residual tumor tissues.

In a previous study, He et al. conducted a comparison of the efficacy and safety of DEB-BACE versus PVA-BACE in treating patients with advanced squamous lung cancer who had failed systemic therapy demonstrated that DEB-BACE significantly extended OS and PFS without increasing the incidence of adverse effects compared to PVA-BACE.²⁷ However, in the present study, DEB-BACE’s median OS and median PFS were slightly shorter than those of other embolic materials, which is inconsistent with the results of the above studies. Possible reasons include: (1) the present study was a meta-analysis of single-group rate, and there were differences in baseline data such as tumor stage, tumor size, age, and Eastern Cooperation Oncology Group score of patients included in different studies; (2) the limited number of controlled studies on various embolization materials means that the results of the subsequent subgroup analyses may lack accuracy; (3) most of the literature included had an insufficient follow-up period, and a large number of patients were still at the end of the follow-up period survived, which may have had an impact on the results of the subgroup analyses. No serious adverse reactions related to BACE occurred in all included studies, demonstrating the safety of this treatment method.

In addition, a study pointed out that in the case of combined hemoptysis in patients with intermediate and advanced lung cancer, especially in central squamous lung cancer, the risk of sudden fatal hemoptysis is much higher than that of other lung cancer types due to its tendency to form cavities.^50,51 For lung cancer patients with hemoptysis, BACE can not only effectively stop hemoptysis but can also significantly enhance the antitumor effect so as to achieve etiological treatment.⁵² The study further indicated that BACE showed better efficacy in treating squamous lung cancer than other types of lung adenocarcinoma.³⁰ Xu and Lin showed that BACE treatment of patients with standard treatment-refractory/ineligible NSCLC significantly prolonged patients’ median OS without increasing the incidence of adverse events.^53,54 Therefore, BACE has undoubtedly become a reliable choice for all types of lung cancer treatment, and its reusable nature allows it to be flexibly combined with other therapeutic means to jointly achieve better therapeutic effects. However, despite the promising application of BACE in the treatment of lung cancer, there is still no conclusion about the selection of its optimal embolic material. The solution to this problem requires more in-depth and detailed studies to further explore and validate.

Limitations of this study: (1) There is still a lack of clinically relevant RCTs, and most of the included studies were non-RCTs, single-arm trials, with a large degree of interstudy heterogeneity, and the heterogeneity did not decrease significantly after subgroup analysis based on the interventions, and it is important to consider that the heterogeneity may arise from the differences in sample size, age of the included patients, disease stage, previous treatment, etc.; (2) the sample sizes of the included studies were restricted, and the overall quality of the evidence was somewhat lacking. Variations in sample size, patient age, disease stage, and prior treatments across studies necessitate cautious interpretation and generalization of the findings; (3) the results of the meta-analysis of the single-group rate were descriptive results, not results of the difference in the comparisons, and the significance of the sensitivity analyses and the publication bias analysis have limited significance; (4) due to the short follow-up time of the included studies, the presence of patients still alive at the end of the follow-up period complicates the accurate assessment of the long-term effects of this treatment approach. Therefore, there is currently uncertainty regarding the long-term benefits of BACE for lung cancer, which may lead to an underestimation of its actual effectiveness. Longer follow-up and further detailed studies are essential to fully grasp the efficacy of BACE in treating lung cancer; (5) not all studies covered all endpoints of interest, and such omissions could be a potential source of bias and thus mislead the results of our analyses. To minimize the impact of this problem, we took active steps to maximize endpoint data collection for each study. This included a deep dive into existing data and attempts to reproduce Kaplan–Meier curves by means of digital reconstruction. In this way, we aim to gain a more complete picture of the endpoints in each study, which will allow us to more accurately assess treatment efficacy and reduce bias due to missing data. Therefore, the conclusions obtained in this study need to be further verified by more high-quality and large-sample clinical studies.

Conclusion

In conclusion, BACE, as a localized treatment, has demonstrated excellent results in the field of lung cancer treatment. Its remarkable therapeutic effect is not only reflected in the effective control of tumor but also in the prolongation of patients’ survival and significant improvement of their quality of life. At the same time, BACE also shows good safety, effectively reduces complications and adverse events during the treatment process, and brings a safer and more reliable treatment option for patients. Therefore, BACE is undoubtedly a superior treatment for patients with NSCLC and is expected to bring better prognosis and quality of life to more patients.

Future Prospects

The future of BACE in lung cancer treatment is promising but requires further exploration. Advancements in both technique and material selection will be critical to optimizing outcomes. Future research should focus on larger, RCTs to overcome current limitations, such as small sample sizes and study heterogeneity, and to confirm the long-term efficacy and safety of BACE. Comparative studies on different embolic materials and their combinations with other therapeutic approaches could offer deeper insights into achieving optimal clinical results. Extending follow-up periods will be vital for accurately assessing the sustained benefits of BACE and refining patient selection criteria. By addressing these research gaps, we can better tailor BACE to individual needs, ultimately enhancing survival rates and quality of life for lung cancer patients.

Footnotes

Authors’ Contributions

Conception and design of study: T.W.; Drafting of article: J.W. and Y.X.

Data Availability

All data produced or analyzed in this study are contained within the published article, with referenced sources listed in the References section.

Disclosure Statement

The authors declare that they have no competing interests.

Funding Information

No funding was received for this article.

References

Bray

, Ferlay

, Soerjomataram

, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018; 68(6):394–424; doi: 10.3322/caac.21492

Thai

, Solomon

, Sequist

, et al. Lung cancer. Lancet, 2021; 398(10299):535–554; doi: 10.1016/s0140-6736(21)00312-3

Arbour

, Riely

. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: A review. JAMA, 2019; 322(8):764–774; doi: 10.1001/jama.2019.11058

Chen

, Zheng

, Baade

, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016; 66(2):115–132; doi: 10.3322/caac.21338

Siegel

, Miller

, Fuchs

, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022; 72(1):7–33; doi: 10.3322/caac.21708

Bray

, Laversanne

, Sung

, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024; 74(3):229–263; doi: 10.3322/caac.21834

Zappa

, Mousa

. Non-small cell lung cancer: Current treatment and future advances. Transl Lung Cancer Res, 2016; 5(3):288–300; doi: 10.2103/7/tlcr.2016.06.07

Chen

, Liu

, Wen

, et al. Non-small cell lung cancer in China. Cancer Commun (Lond), 2022; 42(10):937–970; doi: 10.1002/cac2.12359

Goldstraw

, Chansky

, Crowley

, et al. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC lung cancer staging project: Proposals for revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol, 2016; 11(1):39–51; doi: 10.1016/j.jtho.2015.09.009

10.

Cao

, Chen

, Yu

, et al. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin Med J (Engl), 2021; 134(7):783–791; doi: 10.1097/cm9.0000000000001474

11.

Miller

, Siegel

, Lin

, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin, 2016; 66(4):271–289; doi: 10.3322/caac.21349

12.

Mineo

, Guggino

, Mineo

, et al. Relevance of lymph node micrometastases in radically resected endobronchial carcinoid tumors. Ann Thorac Surg, 2005; 80(2):428–432; doi: 10.1016/j.athoracsur.2005.02.083

13.

Salfity

, Tong

. VATS and minimally invasive resection in early-stage NSCLC. Semin Respir Crit Care Med, 2020; 41(3):335–345; doi: 10.1055/s-0039-3401991

14.

Ettinger

, Wood

, Aisner

, et al. NCCN guidelines® insights: Non-small cell lung cancer, version 2.2023. J Natl Compr Canc Netw, 2023; 21(4):340–350; doi: 10.6004/jnccn.2023.0020

15.

Reboul

, Vincent

, Brewer

, et al. [Concomitant radiochemotherapy for locally advanced bronchial cancers: Current results and prospects]. Cancer Radiother, 1997; 1(2):113–120; doi: 10.1016/s1278-3218(97)83527-5

16.

Curran

Jr , Paulus

, Langer

, et al. Sequential vs. Concurrent chemoradiation for stage III non-small cell lung cancer: Randomized phase III trial RTOG 9410. J Natl Cancer Inst, 2011; 103(19):1452–1460; doi: 10.1093/jnci/djr325

17.

Ahn

, Ahn

, Kim

, et al. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol, 2015; 33(24):2660–2666; doi: 10.1200/jco.2014.60.0130

18.

Liang

, Bi

, Wu

, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: A multicenter randomized phase III trial. Ann Oncol, 2017; 28(4):777–783; doi: 10.1093/annonc/mdx009

19.

Senan

, Brade

, Wang

, et al. PROCLAIM: Randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol, 2016; 34(9):953–962; doi: 10.1200/jco.2015.64.8824

20.

Bittoni

, Arunachalam

, Li

, et al. Real-world treatment patterns, overall survival, and occurrence and costs of adverse events associated with first-line therapies for medicare patients 65 years and older with advanced non-small-cell lung cancer: A retrospective study. Clin Lung Cancer, 2018; 19(5):e629–e645; doi: 10.1016/j.cllc.2018.04.017

21.

Hasegawa

, Kawaguchi

, Kubo

, et al. Ethnic difference in hematological toxicity in patients with non-small cell lung cancer treated with chemotherapy: A pooled analysis on Asian versus non-Asian in phase II and III clinical trials. J Thorac Oncol, 2011; 6(11):1881–1888; doi: 10.1097/JTO.0b013e31822722b6

22.

Zhu

, Zhang

, Jiang

, et al. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer. Ther Adv Respir Dis, 2017; 11(8):301–309; doi: 10.1177/1753465817717169

23.

Liu

, Lin

, Wang

, et al. Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: Comparison of treatment efficacy, safety and quality of life. Eur Rev Med Pharmacol Sci, 2021; 25(6):2554–2566; doi: 10.2635/5/eurrev_202103_25419

24.

Lee

, Lau

, Chin

, et al. Modern diagnostic and therapeutic interventional radiology in lung cancer. J Thorac Dis, 2013; 5(Suppl 5):S511–S23; doi: 10.3978/j.issn.2072-1439.2013.07.27

25.

Chen

, Wang

, Yu

, et al. Combination of computed tomography-guided iodine-125 brachytherapy and bronchial arterial chemoembolization for locally advanced stage III non-small cell lung cancer after failure of concurrent chemoradiotherapy. Lung Cancer, 2020; 146:290–296; doi: 10.1016/j.lungcan.2020.06.010

26.

Chen

, Li

, Jia

, et al. Bronchial artery chemoembolization combined with radioactive iodine-125 seed implantation in the treatment of advanced nonsmall cell lung cancer. J Cancer Res Ther, 2017; 13(4):636–641; doi: 10.4103/jcrt.JCRT_93_17

27.

, Yang

, Zhang

, et al. Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study. Eur J Radiol, 2023; 161:110747; doi: 10.1016/j.ejrad.2023.110747

28.

Liu

, Zhang

, Ren

, et al. Efficacy and safety of drug-eluting bead bronchial arterial chemoembolization plus anlotinib in patients with advanced non-small-cell lung cancer. Front Cell Dev Biol, 2021; 9:768943; doi: 10.3389/fcell.2021.768943

29.

Ren

, Wang

, Li

, et al. The efficacy of drug-eluting bead transarterial chemoembolization loaded with oxaliplatin for the treatment of stage III-IV non-small-cell lung cancer. Acad Radiol, 2022; 29(11):1641–1646; doi: 10.1016/j.acra.2022.01.015

30.

Wang

, Zhang

, Zhou

, et al. Efficacy and safety of 8 spheres plus cisplatin versus vinorelbine plus cisplatin in locally advanced non-small cell lung cancer. Cancer Biother Radiopharm, 2023; 38(5):313–321; doi: 10.1089/cbr.2020.4301

31.

, Bie

, Li

, et al. Drug-eluting bead bronchial arterial chemoembolization with and without microwave ablation for the treatment of advanced and standard treatment-refractory/ineligible non-small cell lung cancer: A comparative study. Front Oncol, 2022; 12:851830; doi: 10.3389/fonc.2022.851830

32.

, Li

Y-M

, Bie

Z-X

, et al. Drug-eluting beads bronchial arterial chemoembolization/bronchial arterial infusion chemotherapy with and without PD-1 blockade for advanced non-small cell lung cancer: A comparative single-center cohort study. Quant Imaging Med Surg, 2023; 13(9):6241–6256; doi: 10.2103/7/qims-23-287

33.

Zhao

, Liu

, Qin

, et al. Efficacy and safety of callispheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study. Front Oncol, 2023; 13:1110917; doi: 10.3389/fonc.2023.1110917

34.

Zhu

, Xu

, Chen

, et al. Bronchial artery chemoembolization with apatinib for treatment of central lung squamous cell carcinoma. J Cancer Res Ther, 2022; 18(5):1432–1435; doi: 10.4103/jcrt.jcrt_2401_21

35.

Zheng

, Chen

, Han

, et al. Cancer incidence and mortality in China, 2022. Zhonghua Zhong Liu Za Zhi, 2024; 46(3):221–231; doi: 10.3760/cma.j.cn112152-20240119-00035

36.

Bie

, Li

, et al. The efficacy of drug-eluting beads bronchial arterial chemoembolization loaded with gemcitabine for treatment of non-small cell lung cancer. Thorac Cancer, 2019; 10(9):1770–1778; doi: 10.1111/1759-7714.13139

37.

Liu

, Li

, et al. Bevacizumab loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy for advanced lung adenocarcinoma. Front Pharmacol, 2023; 14:1170344; doi: 10.3389/fphar.2023.1170344

38.

Zhao

, Tu

, Fan

, et al. Drug-eluting beads-transcatheter arterial chemoembolization with or without iodine-125 treatment is effective and tolerable in treating advanced non-small cell lung cancer patients: A pilot study. Transl Cancer Res, 2020; 9(5):3191–3202; doi: 10.2103/7/tcr.2020.03.64

39.

, Li

, Ren

, et al. The safety and efficacy of oxaliplatin-loaded drug-eluting beads transarterial chemoembolization for the treatment of unresectable or advanced lung cancer. Front Pharmacol, 2022; 13:1079707; doi: 10.3389/fphar.2022.1079707

40.

, Shen

, Chen

, et al. Drug-eluting beads bronchial arterial chemoembolization vs. conventional bronchial arterial chemoembolization in the treatment of advanced non-small cell lung cancer. Front Med (Lausanne), 2023; 10:1201468; doi: 10.3389/fmed.2023.1201468

41.

Nct. PD-1 antibody in addition to bace in patients with NSCLC: A randomised controlled trial. Available from: https://clinicaltrialsgov/show/NCT05605613 2022.

42.

Zhao

, Huang

, Ye

, et al. Therapeutic efficacy of traditional vein chemotherapy and bronchial arterial infusion combining with CIKs on III stage non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 2009; 12(9):1000–1004; doi: 10.3779/j.issn.1009-3419.2009.09.011

43.

Fiorentini

, Sarti

, Carandina

, et al. A review discussing the use of polyethylene glycol microspheres in the treatment of hepatocellular carcinoma. Future Oncol, 2019; 15(7):695–703; doi: 10.2217/fon-2018-0425

44.

Zou

, Zhao

, Zhang

, et al. Pulmonary lesions: Correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression. BMC Med Imaging, 2021; 21(1):158; doi: 10.1186/s12880-021-00692-3

45.

Osaki

, Hanagiri

, Nakanishi

, et al. Bronchial arterial infusion is an effective therapeutic modality for centrally located early-stage lung cancer: Results of a pilot study. Chest, 1999; 115(5):1424–1428; doi: 10.1378/chest.115.5.1424

46.

Kudo

, Ueshima

, Yokosuka

, et al. SILIUS study group. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): A randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol, 2018; 3(6):424–432; doi: 10.1016/s2468-1253(18)30078-5

47.

Lee

, Lee

, Han

, et al. Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil versus transarterial chemoembolization using doxorubicin for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: A retrospective analysis. Ther Adv Med Oncol, 2017; 9(10):615–626; doi: 10.1177/1758834017728018

48.

Jin

, Zhao

, Bai

, et al. Transcatheter arterial chemoembolization improves clinical efficacy and life quality of patients with lung cancer and reduces adverse reactions. Am J Transl Res, 2021; 13(9):10396–10403.

49.

Xie

, Zhou

, Liang

, et al. Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer. J Exp Clin Cancer Res, 2021; 40(1):266; doi: 10.1186/s13046-021-02069-4

50.

Han

, Yoon

, Kim

, et al. Bronchial artery embolization for hemoptysis in primary lung cancer: A retrospective review of 84 patients. J Vasc Interv Radiol, 2019; 30(3):428–434; doi: 10.1016/j.jvir.2018.08.022

51.

Panda

, Bhalla

, Goyal

. Bronchial artery embolization in hemoptysis: A systematic review. Diagn Interv Radiol, 2017; 23(4):307–317; doi: 10.5152/dir.2017.16454

52.

Lorenz

, Navuluri

. Advancements in interventional oncology of the chest: Transarterial chemoembolization and related therapies. Semin Intervent Radiol, 2022; 39(3):253–260; doi: 10.1055/s-0042-1751259

53.

, Li

, Bie

, et al. Standard treatment-refractory/ineligible small cell lung cancer treated with drug-eluting beads bronchial arterial chemoembolization: A retrospective cohort study. Quant Imaging Med Surg, 2023; 13(1):339–351; doi: 10.2103/7/qims-22-530

54.

Lin

, Wang

, Tian

, et al. Drug-eluting beads bronchial arterial chemoembolization in treating relapsed/refractory small cell lung cancer patients: Results from a pilot study. Cancer Manag Res, 2021; 13:6239–6248; doi: 10.2147/cmar.S310115