Meta-analysis compares three lung fiducial marker insertion approaches for stereotactic body radiotherapy

This systematic review and meta-analysis evaluated the clinical performance and safety of three approaches for inserting fiducial markers (FMs) in patients with peripheral pulmonary lesions requiring stereotactic body radiotherapy (SBRT). The analysis synthesized data from 27 observational studies involving a total of 2,065 patients and 4,149 fiducial marker insertions. The population consisted of patients with peripheral pulmonary lesions, though specific demographic characteristics, comorbidities, and lesion characteristics were not reported. The setting for these procedures was also not specified in the included studies.

The three compared interventions were transthoracic, endovascular, and endobronchial approaches for fiducial marker insertion. The analysis did not report specific procedural protocols, equipment details, or operator experience levels for any approach. The comparator was the direct comparison of outcomes between these three insertion techniques, with no single approach designated as a reference standard.

The primary outcomes were clinical performance, measured by inaccurate FM location rate and tracking rate, and per-procedural complications, specifically pneumothorax and hemoptysis. For inaccurate FM location, the lowest rate was observed with nonlinear FMs inserted via endobronchial access, with an effect size of 0.030 (95% CI: 0.004-0.074). Absolute numbers for this outcome were not reported. For tracking rate, all three approaches demonstrated high performance: endobronchial approach 0.975 (95% CI: 0.949-0.994), endovascular approach 0.999 (95% CI: 0.941-1.000), and transthoracic approach 0.985 (95% CI: 0.963-0.998). Absolute numbers for tracking rates were also not reported.

No specific secondary outcomes were reported in this meta-analysis beyond the primary outcomes of clinical performance and per-procedural complications.

Safety findings focused on two per-procedural complications. The transthoracic approach had the highest rate of pneumothorax at 0.342 (95% CI: 0.261-0.427) and hemoptysis at 0.035 (95% CI: 0.015-0.060). Rates for these complications with endovascular and endobronchial approaches were not separately reported. The analysis did not report serious adverse events, procedure-related discontinuations, or tolerability measures. Long-term safety outcomes beyond the per-procedural period were not addressed.

This meta-analysis provides a comparative synthesis of observational data on FM insertion approaches, whereas prior studies have typically examined single approaches in isolation. The finding that all three approaches achieve high tracking rates aligns with previous single-technique reports, but the direct comparison of complication rates across approaches represents a novel contribution to the literature. The identification of transthoracic access as having the highest complication rates provides context for procedural risk-benefit discussions that were previously based on less comprehensive evidence.

Key methodological limitations include the observational nature of all included studies, which introduces potential selection bias and confounding. The analysis did not account for differences in patient characteristics, lesion location and size, operator experience, or institutional protocols across studies. The absence of randomization limits causal inference about the superiority of any approach. Additionally, the meta-analysis did not report on study quality assessment, publication bias, or heterogeneity measures, which affects interpretation of the pooled estimates. The safety assessment was limited to two per-procedural complications without data on other adverse events or long-term outcomes.

Clinical implications suggest that when planning fiducial marker insertion for SBRT, clinicians should consider the trade-off between technical performance and complication risk. The endobronchial approach with nonlinear FMs appears to offer the best balance of accurate placement and lower per-procedural complications based on this observational evidence. However, patient-specific factors such as lesion accessibility, pulmonary function, and bleeding risk should guide individual procedural choices. These findings support multidisciplinary discussion between radiation oncologists and proceduralists when selecting insertion approaches.

Unanswered questions include the comparative effectiveness of these approaches in specific patient subgroups, such as those with central versus peripheral lesions or varying degrees of pulmonary compromise. Long-term outcomes related to FM stability, migration, and impact on SBRT delivery accuracy remain unaddressed. The cost-effectiveness of different approaches and the learning curve associated with each technique were not evaluated. Additionally, the optimal type of fiducial marker (linear versus nonlinear) for each insertion approach requires further investigation through prospective comparative studies.