The use of electromagnetic navigation bronchoscopy-guided microwave ablation in patients with multiple bilateral pulmonary nodules: a retrospective study of 26 cases
Highlight box
Key findings
• The use of electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) is safe and efficacy in treating patients with multiple bilateral ground-glass opacities (GGOs).
• The combination of ENB-guided MWA and video-assisted thoracoscopic surgery (VATS) exhibits advantages over bilateral surgical procedure in certain cases.
What is known and what is new?
• ENB-guided MWA has become a proven therapeutic strategy in treating GGOs, which is recommended for patients with poor pulmonary function.
• The combination of ENB-guided MWA and VATS provided a potential for treatment optimization in patients with multiple bilateral GGOs.
What is the implication, and what should change now?
• Bilateral ENB-guided MWA is feasible in patients who cannot tolerate surgery, and VATS combined with ENB-guided MWA is safe and can also preserve as much pulmonary function as possible.
Introduction
In recent years, the detection rate of ground-glass opacities (GGOs) has increased significantly, and a relative proportion of GGOs would finally be confirmed malignancy pathologically. Although minimally invasive surgical approaches have become the answer for these suspicious GGOs, a consensus on the diagnosis and treatment is still lacking for patients with bilateral multiple GGOs.
Electromagnetic navigation bronchoscopy (ENB) is a recommended minimally invasive technology to approach pulmonary lesions (1), especially for peripheral lesions difficult to reach with bronchoscopy alone (2). To find a more effective interventional treatment for patients with multiple GGOs, thermal ablation therapy has been used in these patients, including radiofrequency ablation and microwave ablation (MWA). Presently, the use of ENB-guided MWA has become a proven therapeutic strategy, which may be particularly advantageous in patients with poor pulmonary function.
Jiang et al. first performed the combination of ENB-guided MWA and thoracoscopic resection on patients with multiple GGOs (3). In this case, the target GGO of ENB-guided MWA was located in the right upper lobe, and, after the procedure, the remaining lesions in left lung were all successfully resected by video-assisted thoracoscopic surgery (VATS). Presently, a total of two studies reported a single-centered systematical application of ENB-guided MWA in multiple, unilateral or bilateral GGOs (4,5). The results indicated that ENB-guided MWA combined with VATS is safe and feasible in patients with multiple GGOs suspected of having multiple primary lung cancers.
In this study, we conducted a retrospective study to investigate the differences in patient characteristics and efficacy among three treatment strategies based on ENB-guided MWA: receiving only ENB-guided MWA, receiving simultaneous VATS and ENB-guided MWA, and receiving VATS followed by a second round of ENB-guided MWA. Our results revealed selection tendencies within different strategies, which provided a theoretical basis for treatment optimization in patients with bilateral GGOs. We present this article in accordance with the PROCESS reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1052/rc).
Methods
Patients and procedures
The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional ethics board of Jiangsu Cancer Hospital (No. JSLMTCR-2020-062) and individual consent for this retrospective analysis was waived. We reviewed a total of 26 patients underwent ENB-guided MWA from Jiangsu Cancer Hospital between December 2020 to February 2023. The clinical criteria for ENB-guided MWA in our center were as follows: (I) bilateral GGOs [pure GGO (pGGO) or mixed GGO (mGGO)] confirmed by chest computed tomography (CT); (II) predominant lesion (in size and solidity) diameter >7 mm and with highly suspicious of malignancy; (III) Eastern Cooperative Oncology Group performance status (PS) of 0 to 2; (IV) no previous history of tumors; (V) no regional lymph nodes or distant metastases observed in the preoperative examination.
We chose ablation or resection for the lesions based on the following principles: (I) for the predominant lesion, we chose VATS or ENB-guided MWA based on cardiopulmonary function, and we would perform ENB-guided biopsy before proceeding the ablation; (II) for the minor lesions in the ipsilateral lung, we preferred surgical resection when performing VATS on the predominant lesion; (III) for the other lesions in the contralateral lung, we conducted ENB-guided MWA. Finally, the result was the formation of three different therapeutic strategies, which were receiving only ENB-guided MWA, simultaneous VATS and ENB-guided MWA, and two-step VATS and ENB-guided MWA (Figure 1A).
ENB-guided MWA and biopsy
In our center, we used SuperDimension navigation system (SuperDimension Inc., Minneapolis, MN, USA) to proceed ENB procedures, and the MWA procedures were performed using the MTC-3 MWA system (Vision-China Medical Devices, Nanjing, China). ENB procedures were carried out as follows: (I) High-resolution chest CT scan data were imported into the system to conduct three-dimensional reconstruction and plan navigation paths for lung and bronchial images (Figure 1B). (II) Six positioning points were set within the virtual bronchial tree reconstructed from imaging, and the images from the fiberoptic bronchoscope (BF-1TQ290, Olympus, Tokyo, Japan) were aligned with the virtual bronchial tree based on these points. (III) The computer automatically planed the path based on the lesion’s position, and the lesion position and size were marked on CT images. (IV) Patients were placed in a supine position under general anesthesia with a laryngeal mask or endotracheal intubation for ventilation. (V) Three magnetic poles were symmetrically placed on the anterior chest, between the sternal angle and the eighth intercostal space on both sides, forming an isosceles triangle layout, above the electromagnetic positioning board. (VI) During navigation, a conventional bilateral bronchial examination was conducted using the fiberoptic bronchoscope, and then the positioning guide tube was inserted into the bronchoscope’s working channel, with the sensor exposed at the front end. (VII) Under real-time navigation, the guide tube was controlled to enter the lesion site, and the lesion was confirmed using an ultrasound probe (Figure 1C). (VIII) Tissue samples were obtained or area staining was performed through the extension working tunnel using biopsy needles, forceps, brush forceps, or fine catheters. (IX) For the ablation procedure, parameters such as tumor size, location, morphology, adjacent structures, access route, and vessel diameter near the nodules were adjusted. Microwave energy at 0 to 100 W power and a frequency of 2,450±50 MHz was used. A microwave antenna (1.8 mm diameter, 1,200 mm effective length, with water circulation cooling system) was inserted into the lesion through the ENB’s working channel. Ablation was conducted with 60 to 80 W power for 4 to 8 minutes per site, guided by cone beam CT.
Intraoperative histopathology testing involved the use of rapid on-site evaluation (ROSE). A cytologist conducted ROSE of specimens, verifying their adequacy, and identifying tumor cells. Whenever feasible, diagnostic suspicion was formed based on this assessment. Following tumor biopsy using ENB, pathology of frozen specimens was promptly carried out, with two levels of each specimen utilized for diagnosis. The frozen sections were analyzed by two senior pathologists, and any discrepancies were resolved by a third senior pathologist.
VATS
The patient-specific surgical planning was based on the size, location, or ENB-guided biopsy of predominant lesions and the lung function reserve. The VATS were performed based on the following principles: (I) anatomical sublobar resection was recommended for the predominant lesion; (II) pGGOs and mGGOs were preferentially treated with wedge resection and segmentectomy, respectively; (III) lobectomy was preferentially chosen for central lesions, especially for mGGOs; (IV) when the lesion is larger than 2 cm, radiologically or ROSE diagnosed as an invasive lesion, which will also be considered lobectomy (Figure 1D).
Follow-up
After undergoing ENB-guided treatment or surgery, all patients received consistent follow-up care, either through regular outpatient visits or via telephone communication. The follow-up period began immediately after the surgery and continued until December 2023. In the first year following surgery, patients underwent chest CT scans, tumor marker assessments, and abdominal ultrasonography every three months. In the second year post-surgery, these evaluations were performed every six months, and subsequently, annually.
Statistical analysis
The analyses were performed utilizing R version 4.3.3. Characteristic data were summarized employing descriptive statistics, encompassing frequency distributions and cross-tabulations for discrete variables, and providing mean, standard deviation, median, interquartile range, minimum, and maximum values for continuous variables.
We visualized the significant differential or differential trend of variables using point-plots (6). To annotate included cases in point-plots, the maximum diameter and number of GGOs of each case were respectively used as the x-axis and y-axis. Then, the median value and distinguished stage were used for the selected continuous and discrete variables, respectively, to distinguish cases. The confidence intervals of ellipsoidal shape were calculated based on the distribution of points’ positions. Finally, all included variables were compared within each group. The distance between the centers of confidence intervals represented the degree of difference between the advantageous samples and the ingroup samples, and the length of distance represented the contribution in the group selection.
Results
Patient and lesion characteristics
A total of 26 patients with bilateral multiple GGOs who underwent ENB-guided MWA were included in this post-analysis. According to the different treatment procedures received by patients, the detailed information of characteristics is summarized in Table 1. All patients underwent preoperative examinations, which included evaluations of cardiopulmonary function, enhanced chest CT scans, head magnetic resonance imaging, bone scans, and positron emission tomography (PET)-CT scans if deemed necessary. Thirteen men and 13 women were included, with an overall mean age was 67.7±10.7 years and a smoking rate of 42.3%. Among male patients, the majority had a history of smoking (10 in 13). In the MWA-only group, there were 32 GGOs with a mean size of 18.2±8.0 mm, comprising 28 pGGOs and 4 mGGOs. The simultaneous VATS-MWA group had 14 GGOs with a mean size of 15.7±5.3 mm, including 7 pGGOs and 7 mGGOs. The two-step VATS-MWA group exhibited 20 GGOs with a mean size of 14.9±7.6 mm, consisting of 9 pGGOs and 11 mGGOs.
Table 1
Variables | MWA-only (n=13) | Simultaneous (n=5) | Two-step (n=8) | P value |
---|---|---|---|---|
Gender | 0.35 | |||
Male | 8 | 1 | 4 | |
Female | 5 | 4 | 4 | |
Age (years) | 0.64 | |||
≥60 | 11 | 5 | 6 | |
<60 | 2 | 0 | 2 | |
Tabaco | 0.13 | |||
Smoking | 7 | 0 | 4 | |
Non-smoking | 6 | 5 | 4 | |
Pulmonary function | <0.001 | |||
FEV1/FVC ratio | 0.75±0.05 | 0.89±0.04 | 0.82±0.06 | |
ECOG PS | 0.06 | |||
0 | 4 | 5 | 5 | |
1 | 8 | 0 | 3 | |
2 | 1 | 0 | 0 | |
Disease pattern | 0.07 | |||
pGGO + pGGO | 10 | 1 | 2 | |
mGGO + pGGO | 2 | 2 | 4 | |
mGGO + mGGO | 1 | 2 | 2 | |
Ablation side | >0.99 | |||
Left | – | 2 | 3 | |
Right | – | 3 | 5 | |
GGO treatment | >0.99 | |||
Number of GGOs by ablation | 32 | 7 | 9 | |
Number of GGOs by resection | – | 7 | 11 | |
Surgical strategy | 0.34 | |||
Wedge resection | – | 1 | 5 | |
Segmentectomy | – | 3 | 2 | |
Lobectomy | – | 1 | 1 | |
Perioperative efficacy | ||||
Ablation time, min | 8±4.3 | 4.6±0.9 | 3.9±1.8 | 0.02 |
Operation time, min | 73.1±16.1 | 108±9.1 | 103.1±19.3/42.5±5.3 | – |
Postoperative hospital stay, d | 1.3±1.1 | 8±4.5 | 4.4±0.5/1.5±0.9 | – |
Postoperative pain, level | 0.9±0.9 | 1.8±0.4 | 1.5±0.8/0.5±0.5 | – |
Complications/adverse events | 0.74 | |||
Pneumonia (grade I) | 1 | 0 | 1 | |
Pneumothorax (grade I) | 0 | 0 | 1 | |
Pneumothorax (grade II) | 1 | 1 | 0 | |
Intraoperative pathology | 0.66 | |||
AAH | 1 | 1 | 0 | |
AIS | 2 | 1 | 2 | |
MIA | 5 | 2 | 1 | |
IA | 1 | 0 | 0 | |
Undetermined | 4 | 1 | 5 | 0.32 |
Postoperative pathology | 0.01 | |||
AAH | 5 | 2 | 1 | |
AIS | 6 | 0 | 1 | |
MIA | 0 | 0 | 4 | |
IA | 2 | 3 | 2 |
Data are expressed as n and mean ± standard deviation. MWA, microwave ablation; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; ECOG PS, Eastern Cooperative Oncology Group performance status; GGO, ground-glass opacity; pGGO, pure GGO; mGGO, mixed GGO; AAH, atypical adenomatous hyperplasia; AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; IA, invasive adenocarcinoma.
Comparison among three treatment groups
According to the characteristics in Table 1, we further compared the differences among three treatment groups. While no significant differences were found in the baseline information, the MWA-only group exhibited the worst pulmonary function (P<0.001) and a trend of poorer performance status (P=0.06). A higher proportion of cases with mGGOs was observed in the simultaneous and two-step groups (P=0.07), although no significant differences were indicated among the treated GGOs. Additionally, although the MWA-only group showed the longest ablation time (P=0.02), a better perioperative efficacy (vs. the simultaneous group) and comparable lower complication rates were revealed compared to the other two groups. There were no significantly different results found in intraoperative pathology and non-detectable rates among these three groups. However, earlier stages were indicated in the postoperative pathology of the simultaneous and two-step groups (P=0.01).
Analysis of ENB-guided procedure selection
Accordingly, we visualized the statistical differences in pulmonary function level, PS score, disease pattern of mGGOs, ablation time length, and postoperative pathology among the various treatment groups (Figure 2, see the “Methods” section). We observed that the three treatment groups exhibit variations across all included point plots. The MWA-only group displayed significantly different trends in pulmonary function, PS, disease pattern, and pathology. Similarly, the simultaneous group exhibited significant differences in pulmonary function, disease pattern, ablation time, and pathology. Notably, the two-step group demonstrated significantly different trends across all indicators. Further, to conduct intra-group analysis to identify the variables contributing most to the grouping, we reorganized the results to visualize the group-based differences (Figure 3). The intra-group analyses indicated that disease pattern plays a key role in the selection of only ENB-guided MWA, while PS score predominantly influences the selection of two-step VATS and ENB-guided MWA.
Discussion
The detection rate of patients presenting as multiple GGOs is increasing (7). The previous research indicated that multiple GGOs are mostly multifocal adenocarcinomas, such as atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (8). The natural history between isolated and multiple GGOs has not been fully revealed, and the selection of appropriate intervention for multiple GGOs remains controversial (9). Surgical resection, particularly via VATS, is regarded as the preferred treatment for multiple GGOs. However, when GGOs are dispersed across different lobes and even involve bilateral lesions, it poses a significant challenge for thoracic surgeons (10). The simultaneous treatment of all lesions presents difficulties for many cases, particularly those with compromised cardiopulmonary function unable to tolerate concurrent resections, and those with bilateral GGOs. Consequently, our center has tried different hybrid procedures designed for those patients with multiple GGOs, particularly those unable to undergo simultaneous surgical resection.
Multiple GGOs could often be categorized as synchronous multiple primary lung cancers (sMPLC). These patients with multiple GGOs or sMPLC faced a risk of incorrect staging from initial imaging studies. Both clinical and radiographic assessments might lead to either over-staging or under-staging. CT scans, when inaccurate, tended to under-stage patients, while PET-CT scans, when incorrect, often over-stage by interpreting a second primary nodule as “consistent with metastasis” (11). Accurate staging typically requires careful evaluation of the mediastinum, often using PET-CT, to ensure no uptake in mediastinal lymph nodes and the absence of extra-thoracic metastases (12). Previous studies explored other therapeutic options, including stereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) (13,14). SBRT was shown to be a safe and effective treatment for patients with multiple GGOs or sMPLC and was considered a viable alternative to surgery. The 1-, 3-, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively (13). Postoperative EGFR-TKI treatment demonstrated efficacy in addressing persistent lesions after surgery, offering significant benefits for patients with more than two remaining lesions, mGGO patterns, or residual lesion diameters ≥8 mm (14).
Presently, few studies reported the systematic application of ENB-guided MWA in patients with multiple GGOs, especially bilateral multiple GGOs. Narsule et al. were the first to report that CT-guided percutaneous thermal ablation of lung tumors, with the assistance of a magnetic navigation system, was effective in reducing the time for the ablation needle to reach its target and the duration of treatment (15). Then, Jiang et al. reported the feasibility of the combination of ENB-guided MWA and VATS on patients with multiple GGOs (3), which showed that ENB-guided MWA combined with VATS is an alternative treatment strategy to deal with multiple GGOs at the same stage of the operation in the specifical population. Further, Qu et al. and Zeng et al. reported the systematical application of ENB-guided MWA with or without VATS in multiple GGOs (4,5), which confirmed that the application of ENB-guided MWA on multiple GGOs is safe and efficient.
In this study, we summarized three therapeutic strategies for patients with bilateral GGOs based on ENB-guided MWA. According to the above-mentioned analyses on ENB-guided procedures (Figure 2), patients could be classified according to the differential status of disease and general condition. When the density or diameter of the predominant lesion is relatively small, the bilateral ENB-guided MWA was the preferred choice for patients with poor general condition. For patients with more severe lesions and good general condition, most cases underwent simultaneous VATS and ENB-guided MWA. For patients with severe lesions and general overall condition, VATS followed by a second stage ENB-guided MWA was recommended. Notably, within the simultaneous VATS-MWA group, one patient underwent a diagnostic ENB-guided biopsy before VATS and ENB-guided MWA, which indicated Biopsy-VATS-MWA process. Therefore, further investigation is required to assess the feasibility of conducting either VATS-MWA or Biopsy-VATS-MWA.
Conclusions
In conclusion, there are several limitations in this study. Firstly, it was a retrospective study with a relatively small sample size. Secondly, our follow-up of patients was limited, and the long-term prognosis still requires validation. Large-scale randomized studies are still needed to conduct further investigations into the efficacy and safety of different treatment procedures. However, the results of our study demonstrate that this systematic hybrid technique, ENB-guided MWA for bilateral multiple GGOs, is both safe and effective. Furthermore, it even exhibits clear advantages over bilateral surgical procedure in certain cases.
Acknowledgments
Funding: The study was supported by
Footnote
Reporting Checklist: The authors have completed the PROCESS reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1052/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1052/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1052/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1052/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. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics board of Jiangsu Cancer Hospital (No. JSLMTCR-2020-062) and individual consent for this retrospective analysis was waived.
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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