Drug-coated balloons (DCB) for symptomatic intracranial atherosclerotic stenosis: a systematic review and meta-analysis

Introduction

As of 2019, stroke was the second leading cause of death worldwide and responsible for approximately 6.55 million deaths annually (1). Intracranial atherosclerotic stenosis (ICAS) is associated with 10% to 20% of ischemic strokes in Western populations, and up to 50% in Eastern populations (2). ICAS is characterized by a chronic inflammatory process that leads to progressive arterial narrowing, resulting in cerebral hypoperfusion and subsequent neurological impairments (3).

The management of ICAS presents unique challenges, particularly concerning in-stent restenosis, a complication often seen after interventions like angioplasty and stenting (4). This restenosis is primarily due to intimal hyperplasia and smooth muscle cell proliferation, which are exacerbated by mechanical trauma from dilation, the thrombogenic nature of the stents, and localized inflammatory responses (5).

To address these complications, drug-coated balloons (DCBs) have been introduced as an innovative solution. DCBs are designed to deliver a uniform dose of antiproliferative drugs directly to the arterial wall during the angioplasty procedure, aiming to prevent the cellular proliferation that leads to restenosis, defined as the recurrence of stenosis that often necessitates repeat intervention and is associated with increased risk for patients (6).

Recent studies have begun to explore the potential benefits of DCBs over traditional percutaneous transluminal angioplasty and stenting, and results suggest that DCBs may offer superior outcomes in the treatment of ICAS (7). However, despite promising results, there is currently insufficient evidence to formally integrate DCBs into existing treatment guidelines for ICAS. Previous systematic reviews and meta-analyses have shown that DCBs demonstrate significant potential as an effective therapeutic option for symptomatic ICAS in clinical practice, with lower restenosis rates compared with conventional endovascular approaches while maintaining comparable safety profiles (8). However, the lack of prospective studies and detail postoperative outcomes such as degree of stenosis limits the interpretability and strength of the evidence.

This systematic review and meta-analysis aimed to thoroughly evaluate the efficacy of DCBs for the treatment of ICAS, with an emphasis on restenosis rate. By consolidating and analyzing data from recent studies, this review seeks to provide a clearer understanding of the role of DCBs in the management of intracranial atherosclerosis and to inform future clinical practice guidelines. We present this article in accordance with the PRISMA reporting checklist (9) (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-410/rc).

Methods

Search strategy

A literature search of PubMed, EMBASE, and Cochrane CENTRAL was conducted using keyword combinations including “symptomatic intracranial atherosclerotic stenosis” and “drug-coated balloons”. The databases were searched from inception to April 13, 2025 (date of search). In addition, the reference lists of included studies were manually searched to identify other potentially relevant studies. No language restrictions were applied.

Selection criteria

This systematic review and meta-analysis was performed in accordance with the PICOS criteria (participants, intervention, comparison, outcomes, study design) (10). Eligible studies were those that included patients ≥18 years old diagnosed with symptomatic ICAS. The intervention (I) involved DCBs. For comparative studies, the control group (C) consisted of standard medical therapy, conventional balloon angioplasty, or conventional stenting (e.g., bare metal stents). Single-arm studies without a comparison group were also eligible to allow estimation of pooled clinical outcomes following DCB treatment. The outcomes (O) of interest were restenosis rates. Only cohort and case-control studies and randomized controlled trials (RCTs) were considered for inclusion (S).

Reviews, letters, comments, editorials, case reports, proceedings, personal communications, conference abstracts, studies without quantitative outcomes of interest, and non-human studies were excluded. The eligibility of studies for inclusion was confirmed by two independent reviewers, and a third reviewer was consulted where there was uncertainty regarding eligibility.

This systematic review and meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251102102.

Main outcome measures and data extraction

The primary outcomes of the study were restenosis rate and degree of stenosis after DCB treatment. In cases where the mean and standard deviation (SD) were not reported and only the median and interquartile ranges (IQRs) were provided, the mean and SD were estimated using the method proposed by previous studies (11,12). Data extracted included the name of the first author, year of publication, study design, number of patients, age, percentage of males, medical history, smoking history, stenosis location, qualifying event, and follow-up duration. Additionally, restenosis rate, technical success rate, degree of stenosis before and after intervention, and postprocedural stroke, transient ischemic attack (13) and death within 30 days were also recorded. Extracted data were stored in Excel. Data extraction was performed independently by two reviewers; and any disagreements were resolved through discussion with a third reviewer.

Ethics statement

This systematic review and meta-analysis neither required nor used raw patient data and private information; therefore, approval of the protocol by the hospital Institutional Review Board (IRB) and informed consent from study subjects were waived.

Statistical analysis

The primary outcomes were the restenosis rate and degree of stenosis after DCB treatment. To assess the overall clinical efficacy, data from all included studies were pooled. The restenosis rate was evaluated as a pooled proportion with 95% confidence interval (CI), and the degree of stenosis after treatment as a pooled mean with 95% CI. Furthermore, for comparative studies, we further analyzed the differences between the DCB and non-DCB groups by calculating the odds ratio (OR) for the restenosis rate and mean difference (MD) for the degree of stenosis after treatment. Heterogeneity among the studies was evaluated using the Cochran Q test and I² statistic. An I² value ≥50% was considered to indicate heterogeneity and a random effects model of analysis was used. When I² was <50% a fixed effects model of analysis was used. Forest plots were generated to present individual study estimates and pooled effect sizes with 95% CIs. Subgroup analyses were stratified by follow-up duration and age to explore potential sources of heterogeneity. Publication bias was evaluated using funnel plots and statistically assessed by Egger’s regression test. All analyses were two-sided and the significance level was α =0.05. All analyses were performed using R Studio 4.3.2 with the packages “meta”, “dmetar”, and “metafor”.

Risk of bias assessment

Three different tools were used to assess the risk of bias in the included studies. The quality assessment was performed by two independent reviewers, with a third reviewer available to resolve any disagreements. For single-arm studies, methodological quality was assessed using the Agency for Healthcare Research and Quality (AHRQ) methodology checklist. This tool comprises 11 items, each rated as “Yes”, “No”, or “Unclear”. Items rated as “Yes” receive 1 point, whereas those rated as “No” or “Unclear” receive 0 points. Based on the total score, studies are categorized as good (8–11 points), fair (4–7 points), or poor (0–3 points) (14).

The quality of the non-randomized comparative studies was assessed using the Newcastle-Ottawa Scale (NOS) (https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp), following the guidelines of the Cochrane Non-Randomized Studies Methods Working Group. The cohort version of the NOS was used. The NOS assigns up to 9 points per study, with 4 points for cohort selection, 2 points for comparability based on design and analysis, and 3 points for outcome ascertainment. Each criterion is awarded one star for high quality, except for comparability, which can receive up to 2 stars. The total score ranges from 0 to 9, with 7–9 indicating high quality and 4–6 representing medium quality.

The Cochrane Collaboration tool was used to assess the RCTs. The tool assesses risk of bias via seven different criteria: selection bias (i.e., random sequence generation and allocation concealment), performance bias (i.e., blinding of participants and personnel), detection bias (i.e., blinding of outcome assessment), attrition bias (i.e., incomplete outcome), reporting bias (i.e., selective outcome reporting), and inclusion of intention-to-treat analysis (15).

Results

Study selection

A total of 88 records were identified through the database searches. After removing duplicates, 71 records remained. Screening by title and abstract resulted in the exclusion of 41 records: five due to the lack of full text availability, 20 for being reviews or conference abstracts, seven as case reports, eight for not focusing on DCB, and one was a study protocol. This left 30 articles of which the full text was reviewed. Ultimately, 26 studies were included in the systematic review for qualitative analysis and meta-analysis for quantitative synthesis (Figure 1).

Figure 1 PRISMA flow diagram of the study selection process. DCB, drug-coated balloon.

Characteristics of included studies

The study characteristics are summarized in Table 1. Of the 26 studies, two were RCTs (33,37), two were prospective cohort studies (26,38), and the other 22 studies were retrospective cohort studies (7,13,16-25,27-32,34-36,39). The studies spanned from 2019 to 2025, and included varying numbers of patients, from as few as 7 to as many as 242 participants. There were a total of 1,489 patients in the 26 studies. The mean age of the patients ranged from 28 to 73 years, indicating a broad age distribution. The majority of studies had a predominance of male patients, with percentages ranging from 54% to 100%. Common medical histories across these studies included hypertension, diabetes mellitus, dyslipidemia, and coronary artery disease, with hypertension the most frequently reported condition. Smoking history ranged from 20% to 86%. The location of stenosis varied across studies, but primarily involved the internal carotid artery (32), the middle cerebral artery (MCA), and the intracranial vertebral artery (IVA). Follow-up durations also varied, from a minimum of 3 months to a maximum of 26 months (Table 1).

Outcomes reported by the 26 studies, including restenosis rate, definitions and diagnostic criteria for restenosis, and degree of stenosis after intervention, are summarized in Table 2.

Meta-analysis

Restenosis rate from all included studies

Eighteen studies reported the restenosis rate after DCB treatment (7,13,16,18,19,21,22,25-27,31,33-39). Heterogeneity among studies was low (I²=26.8%), and a fixed effects model of analysis was used. The pooled restenosis rate was 11% (95% CI: 9–13%) (Figure 2).

Figure 2 Meta-analysis of the restenosis rate after DCB treatment. CI, confidence interval; DCB, drug-coated balloon.

Degree of stenosis after DCB treatment from all included studies

Seventeen studies reported the degree of stenosis after DCB treatment (13,16,17,19,20,22,23,26,27,29-32,34-36,38). High heterogeneity was detected (I²=93.9%), thus a random effects model of analysis was used. The pooled mean degree of stenosis after DCB treatment was 34.34% (95% CI: 29.85–38.84%) (Figure 3).

Figure 3 Meta-analysis of the degree of stenosis after DCB treatment. CI, confidence interval; DCB, drug-coated balloon; SD, standard deviation.

Restenosis rate compared between DCB and non-DCB

Seven studies compared restenosis rates between DCB treatment and non-DCB treatments (all were BMS) (33-39). No heterogeneity was detected (I²=0%), and thus a fixed effects model of analysis was used. The pooled results indicated that DCB treatment was associated with a significantly lower restenosis rate than non-DCB treatment, with a pooled OR of 0.26 (95% CI: 0.16 to 0.44) (Figure 4).

Figure 4 Meta-analysis of the restenosis rate in comparative studies. CI, confidence interval; OR, odds ratio.

Degree of stenosis in comparative studies

Four studies compared the post-treatment degree of stenosis between DCB and non-DCB groups (34-36,38). Heterogeneity was detected (I²=92.5%) and thus a random effects model of analysis was used. The meta-analysis showed no significant difference between DCB and non-DCB treatments (pooled MD =14.58; 95% CI: −5.98 to 35.14) (Figure 5).

Figure 5 Meta-analysis of the degree of stenosis in comparative studies. CI, confidence interval; MD, mean difference; SD, standard deviation.

Subgroup analyses

In the subgroup analysis based on follow-up duration, the pooled restenosis rate after DCB treatment was 13% (95% CI: 9–17%) for the 6–8 months follow-up period and 11% (95% CI: 7–16%) for the 9–12 months period (Figure 6). The pooled mean degree of stenosis after DCB treatment for the 6 to 8 months follow-up period was 35.46 (95% CI: 32.36 to 38.56), and for the 9 to 12 months follow-up period was 30.20 (95% CI: 24.04 to 36.35) (Figure 7).

Figure 6 Subgroup meta-analysis for restenosis rate after DCB treatment by follow-up duration (6–8 vs. 9–12 months). CI, confidence interval; DCB, drug-coated balloon.

Figure 7 Subgroup meta-analysis for degree of stenosis after DCB treatment by follow-up duration (6–8 vs. 9–12 months). CI, confidence interval; DCB, drug-coated balloon; SE, standard error.

When stratified by a mean age of 60 years, the pooled restenosis rate was 12% (95% CI: 9–16%) in studies with a mean age <60 years and 9% (95% CI: 7–13%) in those with a mean age ≥60 years (Figure S1). The pooled mean degree of stenosis after DCB treatment was lower in studies with a mean patient age <60 years (26.87, 95% CI: 23.39 to 30.36) than in those with age ≥60 years (40.31, 95% CI: 35.31 to 45.30) (Figure S2).

Publication bias analysis

The funnel plot for the assessment of publication bias in studies of the restenosis rate after DCB treatment is shown in Figure 8A. The plot appears symmetric, and Egger’s regression test revealed an absence of publication bias (P=0.14). The funnel plots for the assessment of publication bias in studies reporting the degree of stenosis after DCB treatment are shown in Figure 8B. The data points in the funnel plot appear to be graphically symmetric, and Egger’s regression test showed no evidence of publication bias (P=0.99).

Figure 8 Publication bias analysis of (A) the restenosis rate after DCB treatment and (B) the degree of stenosis after DCB treatment. DCB, drug-coated balloon.

Quality assessment

Among the 19 single-arm studies, the majority were classified as having “Fair” quality, while four studies were rated as “Good” (Table S1). However, limitations included single-center design, non-consecutive recruitment, and limited follow-up reporting. Overall, the majority met key methodological criteria, supporting acceptable study quality. For the five non-randomized comparative studies, NOS scores ranged from 6 to 9, with five studies rated as high quality (scores ≥7), primarily due to strong cohort selection and outcome assessment (Table S2). For the two RCTs, risk of bias is relatively low in random sequence generation, incomplete outcome data and selective reporting, while risk of bias is relatively high in allocation concealment and blinding of participants and personnel (Figure S3).

Discussion

This systematic review and meta-analysis evaluated the efficacy of DCBs for the treatment of ICAS. The meta-analysis of single-arm studies indicated a low pooled restenosis rate of 11% after DCB treatment. Before and after comparisons within the DCB treatment groups revealed a significant reduction in the degree of stenosis. The pooled degree of stenosis after DCB treatment was 34.34%, indicating that post-DCB residual stenosis generally remained modest. This level of residual narrowing suggests a reasonable degree of vessel patency, which could support improved intracranial blood flow and reduced recurrence risk, although any potential clinical implications should be interpreted cautiously and confirmed in future outcome-focused studies. Furthermore, the analysis of comparative studies showed that DCBs had a significantly lower restenosis rate compared to non-DCB interventions. However, when comparing the degree of stenosis between DCB and non-DCB groups, no significant difference was observed. Thus, treatment with DCBs may be associated with low restenosis rates and could represent a potential alternative to traditional approaches for treating ICAS, although these findings should be interpreted cautiously given the substantial heterogeneity across studies. The potential superiority of DCBs over conventional balloon angioplasty or bare metal stents may relate to their localized delivery of antiproliferative agents, most commonly paclitaxel, which inhibits smooth muscle cell proliferation and neointimal hyperplasia—key mechanisms underlying restenosis. Unlike stents, DCBs avoid permanent metallic implantation, thereby reducing chronic vessel irritation and stent-related inflammatory responses (40). However, although these mechanisms are biologically plausible, direct mechanistic evidence in intracranial vessels remains limited. Considerable heterogeneity—particularly in studies reporting post-treatment stenosis—was observed. Our subgroup analyses helped explore potential sources of this variability, but heterogeneity persisted, suggesting that unmeasured or unreported factors across the original studies may have contributed to these differences. This limitation underscores the need for more standardized reporting and prospective comparative trials to clarify the effectiveness of DCBs in ICAS.

ICAS is a serious condition and one of the most frequent causes of stroke worldwide, especially in Asian populations (41,42). While the pathophysiology of ICAS differs from that of extracranial atherosclerosis (ECAS), and some management strategies also differ, many approaches overlap, including modification of lifestyle and dietary factors, cholesterol reduction, and the use of antiplatelet therapies (41,42). Notably, ICAS and ECAS share many risk factors such as hypertension, smoking, diabetes, and hyperlipidemia (43). In addition, advances in imaging such as high-resolution magnetic resonance imaging (HR-MRI) are useful for identifying ICAS and markedly stenotic vessels (41). The primary goal of ICAS management is to reduce the risk of stroke (43,44).

The optimal management for patients with severe, symptomatic ICAS remains unclear. Current treatment strategies primarily rely on intensive medical therapy to control vascular risk factors, with endovascular approaches considered only in selected cases (44,45). Although both medical therapy and endovascular treatments—including balloon angioplasty and stenting—have been investigated, no clear consensus has been established regarding the most effective strategy (45-49). While aggressive medical management has demonstrated superiority over stenting as an initial treatment, medically managed patients who experience recurrent stroke may face a higher risk of severe or fatal outcomes (44).

Early studies reported that endovascular treatment, including stenting and angioplasty, was associated with relatively high complication rates and showed no benefit over aggressive medical therapy (42-44). However, advances in imaging and endovascular devices have renewed interest in endovascular treatment for selected patients with ICAS (42-44). A major limitation of stenting or conventional angioplasty is the risk of restenosis (44,50,51). The development of drug-eluting stents (DES) and DCBs aims to mitigate this issue, although current evidence remains mixed and further studies are needed to clarify their impact on clinical outcomes (42-44,50).

DCBs are a relatively new development aimed at reducing restenosis after endovascular treatment of ICAS (51). However, the current evidence base for their use in ICAS remains limited (51). While the use of antiproliferative drug-delivery devices in intracranial vessels is not unprecedented, it is important to distinguish DCBs from other drug-eluting technologies. Dharia et al. (49) performed a 2024 meta-analysis evaluating DES—not DCBs—for the treatment of ICAS. Their analysis of 14 studies involving 607 patients (640 lesions) suggested that DES may reduce in-stent restenosis with an acceptable safety profile. Nevertheless, outcomes from DES studies cannot be directly extrapolated to DCBs, as the mechanisms of drug delivery, vascular healing responses, and restenosis dynamics differ between these technologies. Although a few studies have compared DES and DCBs in intracranial vessels and reported broadly similar restenosis outcomes (52-54), the available data remain limited and heterogeneous, underscoring the need for dedicated evaluations of DCB performance in ICAS.

In an article published in 2021 Gruber et al. (55) reviewed the rationale and outcomes of using DCBs for the treatment of high-grade intracranial stenosis. The authors concluded that DCBs are an alternative treatment option compared to other used at the time (e.g., BMSs), and their use was associated with low restenosis and complication rates. However, the authors acknowledged that prospective studies are need to confirm their effectiveness, indications, and the best drug for the balloon coating.

Since 2021, a number of systematic reviews and meta-analyses have been published examining the use of DCBs for the treatment of ICAS. A study published in 2022 by Li et al. (56) examined 9 studies with a total of 224 patients with ICAS treated with DCBs. The median follow-up ranged from 3 to 10.7 months, the pooled incidence of restenosis was 5.7% (P=0.516), and the pooled periprocedural complication rate was 5.9% (P=0.649). The authors concluded that DCBs appeared to be safe and effective; however, they stated the quality of evidence was low. A systematic review and meta-analysis published in 2023 specifically examined DCBs for the treatment of vertebral artery origin stenosis (57). The analysis included 7 studies with 159 patients with a median follow-up of 6 to 14 months. The pooled restenosis rate was 12% and the perioperative complication rate was 3%. Consistent with prior reports, the authors concluded that DCBs have potential for the treatment of intracranial stenosis, but randomized controlled studies with larger numbers of patients are needed.

Substantial heterogeneity was observed in several outcomes, particularly in the pooled analysis for degree of stenosis after DCB treatment. The high I² values suggest considerable variability between studies that cannot be attributed to chance alone. This heterogeneity may stem from multiple sources. Variability in patient populations, lesion characteristics, baseline stenosis severity, procedural protocols (e.g., balloon type, inflation duration, and drug coating), and imaging modalities likely contributed to inconsistencies in outcome assessment and restenosis detection across studies. Second, the follow-up duration varied widely, ranging from 3 to 26 months, which may impact restenosis detection rates and treatment outcomes. Finally, operator experience and institutional preferences may also have played a role, especially given the learning curve associated with endovascular procedures in intracranial vessels. These sources of heterogeneity underscore the importance of standardizing definitions, procedural techniques, and outcome assessments in future research to ensure greater comparability across studies. Future studies adopting standardized definitions and assessment methods for restenosis would improve comparability and strengthen the evidence base.

Although not the primary focus of this meta-analysis, it is important to recognize that advances in imaging technology such as HR-MRI and high-resolution vessel wall MRI (VWMRI) have provided the ability to visualize treatment outcomes and changes in treated vessels over time (58). Meng et al. (20) used VWMRI to evaluate plaque modification and stabilization after treatment of ICAS lesions with DCBs. The authors reported at after DCB treatment hyperintense plaques and vessel wall thickening decreased over time, while a similar but non-significant trend was observed for prominent wall enhancement.

As previously mentioned, intracranial in-stent restenosis represents a serious problem in patients with ICAS who have been treated with stents. Notably, pathophysiology and treatment response of in-stent restenosis differ from that of native ICAS. While few studies have examined the role of DCBs for the treatment of in-stent restenosis, Xue et al. (59) retrospectively reviewed the records of five patients who were treated with paclitaxel-coated balloon angioplasty for in-stent restenosis. The authors reported a 100% procedural success rate, a decrease in the degree of in-stent stenosis from a mean of 72% preoperatively to 34% postoperatively, and that a majority of patients did not experience restenosis on long-term follow-up. Previous meta-analyses have reported similar patterns; however, they did not include prospective studies (8). Although a limited number of prospective and RCTs were incorporated in our analysis, the available evidence remains insufficient and restricts more in-depth exploration. Nevertheless, these findings may help inform clinical decision-making and support appropriate patient selection for DCB treatment. Further well-designed, large-scale RCTs are still needed to confirm these results and to establish causal relationships. More recently, Tao et al. published a larger systematic review and meta-analysis that included 22 studies and primarily focused on restenosis rates, perioperative safety, and comparative outcomes between DCB, balloon angioplasty, and stenting (8). While their analysis provided important evidence supporting the safety and efficacy of DCB treatment, our study further expands the literature by incorporating more recently published studies, a larger pooled patient population, and a broader time span. In addition, our analysis provides a more detailed quantitative evaluation of post-treatment residual stenosis as an anatomical efficacy outcome, offering further insight into postprocedural vessel patency beyond restenosis and safety endpoints alone. However, the substantial heterogeneity observed in stenosis-related outcomes limits definitive interpretation, underscoring the need for standardized restenosis definitions and more rigorous prospective comparative studies.

Lastly, although a limited number of prospective and RCTs were incorporated in our analysis, the available evidence remains insufficient and restricts more in-depth exploration. Nevertheless, these findings may help inform clinical decision-making and support appropriate patient selection for DCB treatment. Further well-designed, large-scale RCTs are still needed to confirm these results and to establish causal relationships.

Strengths and limitations

Strengths of this systematic review and meta-analysis include a substantial sample size, enhancing the robustness of the results. A subgroup analysis by follow-up duration was conducted and it helped explore heterogeneity and demonstrated consistent restenosis rates across time intervals, enhancing result interpretability. In addition, an age-based subgroup analysis was performed to further investigate potential sources of heterogeneity, although residual variability remained. no evidence of publication bias was detected, further supporting the reliability of the pooled estimates.

However, there are also limitations that must be considered. The retrospective nature of most included studies could introduce biases related to data collection and patient selection. The predominance of single-arm studies restricts the ability to directly compare DCBs with standard treatment methods under controlled conditions. The predominance of non-randomized studies limits causal inference and the level of evidence. Furthermore, the heterogeneity detected in some outcomes may complicate the interpretation of the results. Notably, we did not separately analyse the initial severity of stenosis (baseline grade), which could influence treatment outcomes, because most original studies did not clearly stratify baseline stenosis severity, making further subgroup analysis infeasible. These issues underscore the need for more RCTs to provide higher-quality evidence, which could more definitively validate the efficacy of DCBs and support their integration into clinical practice.

Conclusions

The results of this systematic review and meta-analysis indicate that DCBs are associated with an overall low restenosis rate, and a reduced risk of restenosis compared to non-DCB treatments. However, due to considerable heterogeneity across the studies and the predominance of retrospective single arm studies, these findings should be interpreted with caution. To verify the long-term efficacy of DCBs for intracranial atherosclerosis, further well-designed RCTs with extended follow-up periods are necessary.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-410/rc

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-410/prf

Funding: This study was funded by the Chang Gung Memorial Hospital (project No. CMRPG3P0691 to C.C.C.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-410/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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