Introduction

Lung cancer is a common malignancy that has a poor prognosis and poses a serious risk to the health of the general public.1 Approximately 85% of all lung cancer cases are non-small cell lung cancer (NSCLC), making it the most prevalent kind.2 3 Early-stage NSCLC is primarily treated with surgery; however, most cases are intermediate to advance at the time of initial diagnosis, and patients miss out on the chance to undergo surgery.4 Different treatment regimens are available for different NSCLC stages, and most regimens include a combination of chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, each of these treatment approaches has its advantages and disadvantages,5 6 and effective treatment alternatives for NSCLC are still urgently needed.

Angiogenesis is a key factor in the growth and proliferation of solid tumours.7 Transvascular intervention is an important approach for treating solid tumours.8 Currently, transarterial interventions are the most widely used in liver tumours and have achieved very good results.9 Transarterial interventions have also been used in colorectal cancer and gastric cancer, and the results are satisfactory.10 11 Transarterial interventions are equally applicable in the treatment of lung cancer.12 The difference between lung cancer and other solid tumours is that lung cancer has two sets of arterial blood supply; however, current studies have shown that lung cancer is mainly supplied blood by the arteries for body circulation (bronchial arteries), and bronchial artery is the main target vessel for transarterial interventions.13–15 Through the first-pass effect of drugs and embolisation of blood vessels, the effect of drugs is enhanced and the blood supply to the tumour is reduced to inhibit tumour growth.16 New embolic materials have emerged as a result of recent developments in materials science, with drug-eluting beads (DEBs) being one of the most brilliant materials.17 DEB bronchial artery chemoembolisation (DEB-BACE) is the technique of using DEBs loaded with chemotherapeutic drugs for BACE.18 19 DEB-BACE has been successfully employed in various advanced lung cancer18 20 and has demonstrated very good therapeutic efficacy and safety.21 However, current studies on the use of DEB-BACE have small sample sizes,22 and no evidence-based benefit of DEB-BACE compared with other treatment modalities has been established. Thus, this study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC.

Materials and methods

Before conducting a meta-analysis to assess the role of DEB-BACE in the treatment of NSCLC, we finished the protocol for the meta-analysis. This protocol was prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA).23 PRISMA statements will be followed when drafting the final meta-analysis.24 This proposal was submitted online to the PROSPERO platform with registration number CRD42023411392.

Information sources

Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases are the sources of information identified for this protocol, and these will be searched in November 2024 for relevant reports that meet the aims of the study. References of relevant reviews will also be screened for further eligible reports.

Search strategy

GY created search strategies for the relevant databases based on the research objectives, and WZ reviewed the search strategies and collaborated with GY to improve them. No language and date constraints will be imposed when searching the relevant databases. The following are the strategies for searching via PubMed:

#1 “Carcinoma, Non-Small-Cell Lung” [Mesh] OR “Carcinoma, Non Small Cell Lung” OR “Carcinomas, Non-Small-Cell Lung” OR “Lung Carcinoma, Non-Small-Cell” OR “Lung Carcinomas, Non-Small-Cell” OR “Non-Small-Cell Lung Carcinomas” OR “Nonsmall Cell Lung Cancer” OR “Non-Small-Cell Lung Carcinoma” OR “Non Small Cell Lung Carcinoma” OR “Carcinoma, Non-Small Cell Lung” OR “Non-Small Cell Lung Cancer” OR “NSCLC.”

#2 DEB-TACE OR DEB-BACE OR “Drug-Eluting Bead Bronchial Arterial Chemoembolization” OR “Bronchial artery chemoembolization with drug-eluting beads” OR “Microsphere” OR “embosphere” OR “hepasphere” OR “callisphere” OR “drug-eluting beads” OR “DEB” OR “drug-eluting.”

#3 #1 AND #2

The search strategies for the Chinese databases are displayed in online supplemental file 1.

Eligibility criteriaTypes of studies

Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English will not be considered.

Participants

The participants will be those with pathologically confirmed NSCLC who are being treated with DEB-BACE without regard for the combined chemotherapy regimen. No restrictions on patient age, sex or ethnicity will be imposed.

Interventions

This study focuses on DEB-BACE as the intervention.

Control

Treatment modalities that do not include DEB-BACE are the control measures.

Outcomes

The primary outcomes will include the overall survival (OS) and progression-free survival (PFS) and secondary outcomes will be the objective response rate (ORR), disease control rate (DCR) and adverse events (AEs).

Study selection

EndNote V.X9.2 will import the literature found through searches in pertinent databases for additional review. First, duplicates will be eliminated, those whose title and abstract are unrelated to the study subject will be eliminated, and those that will satisfy the inclusion requirements will be kept by reading the entire text. Two researchers (GY and YS) will independently choose the studies, and if their results do not match, a debate will be held to reach a consensus.

Data extraction

The two researchers previously mentioned will also carry out data extraction from studies that meet the requirements after screening. Conflicts will be settled by discussions. The first author of the included studies, year of publication, country where the study was conducted, study type, sample size, patient sex, age, tumour classification, tumour stage, number of treatment lines, chemotherapy regimens, size of the beads, chemotherapeutic agents loaded to the beads, the lesion status (postradiation or postchemotherapy or postimmunotherapy or native), concomitant treatment regimens (intra-arterial chemotherapy infusion or chemotherapy or immunotherapy), times of DEB-BACE, median OS and PFS with the corresponding HRs, ORR, DCR and AEs will be extracted from the included studies.

Risk of bias

The risk of bias for each included study will be assessed independently by the same researchers using the Cochrane Handbook for Systematic Reviews of Interventions.25 Selection, performance, detection, attrition, reporting and other biases will be used to assess the risk of bias.

Publication bias

Funnel plots and Egger’s test will be employed to evaluate publication bias when more than 10 eligible papers are included.26 If a study is suspected of publication bias, the study’s corresponding author will be contacted to collect more information. If publication bias is proven, the fill-and-trim procedure will be used to conduct a more thorough analysis.27

Evidence evaluation

The Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the strength of the body of evidence.28 Four categories—high, moderate, low and very low—will be used to classify the quality of evidence.

Statistical analysis

For the statistical analysis of data, RevMan V.5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) will be used. If only Kaplan-Meier curves are displayed in the original research and the median PFS and/or OS with HRs are not directly presented, survival statistics data will be extracted from the Kaplan-Meier curves using Engauge Digitizer V.4.1. We will estimate pooled ORs for various AEs, risk ratios (RRs) for ORRs and DCRs, and HRs for OS and PFS. To assess the heterogeneity between studies, Q-statistic will be used.29 When I2>50% or p<0.1 for the Q-statistic, heterogeneity between studies will be considered statistically significant. When significant heterogeneity exists between studies, a random-effects model will be used to examine the data; otherwise, a fixed-effects model will be used. A statistical difference will be defined as a p<0.05. A pooled HR of >1 will denote a higher risk of disease progression or mortality after DEB-BACE treatment; a pooled RR of >1 will denote a higher overall response, and a pooled OR of >1 will denote a higher level of toxicity of DEB-BACE treatment.

Subgroup analysis

Subgroup analyses will be performed to further investigate the origins of heterogeneity where interstudy heterogeneity is significantly substantial and adequate data are available for the pertinent parameters. The study type, patient sex, age, tumour classification, tumour stage, number of treatment lines, chemotherapeutic regimens, size of the beads, chemotherapeutic agents loaded to the beads, the lesion status, concomitant treatment regimens and times of DEB-BACE will be used to separate the pertinent subgroups. If sufficient data are available, we will consider multivariate analysis where the patients were treated with concomitant treatment with intraarterial chemotherapy infusion or chemotherapy or immunotherapy.

Sensitivity analysis

By excluding studies with a high risk of bias, a sensitivity analysis will be performed to assess the dependability and robustness of the results of the aggregation. A sensitivity analysis to evaluate whether the study is a high-risk study involves deleting one study and providing the analysis results with and without this study.

Patient and public involvement

None.

Ethics and dissemination

This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study.