The efficacy and safety of improved laser ablation in the lung: a pilot study

Introduction

Thermal ablation (TA), as a minimally invasive technique, has been increasingly used in the treatment of lung cancers (1). TA mainly includes radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA), which utilize probes to reach the tumor and directly kill tumor cells through the biological thermal effect (2,3). RFA is the most widely used ablation technique for treating solid tumors and was first introduced for lung cancer treatment in 2000 (4). During RFA, electrical and thermal conductivity can be affected by charring tissue formed around the electrode during ablation (5). The “heat sink” phenomenon poses another challenge (6,7); large blood vessels and airways near the ablation zone can dissipate heat, lowering the temperature below the lethal threshold and thereby reducing ablation efficacy. This effect becomes significant when vessels exceed 4 mm in diameter (8). MWA offers higher convection and reduced heat sink effects in the lungs. However, MWA has ongoing challenges (9-11): (I) a learning curve is required to use MWA safely, as it can produce larger ablation zones compared to RFA (12); and (II) clinical systems vary widely in antenna design, wavelength, frequency, power, and cooling methods, resulting in differing performance characteristics and complicating the interpretation and predictability of clinical outcomes across devices from different manufacturers (13).

In comparison, the clinical development and application of LA for lung tumors are relatively limited. The most commonly used LA system employs a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with a wavelength of 1,064 nm (14). The primary characteristics of LA include (15,16): (I) small ablation zones; (II) short ablation times due to the instantaneous release of laser energy; and (III) the use of a 21-gauge Chiba needle to introduce the optical fiber, which minimizes complications such as hemorrhage. LA is particularly effective for tumors with the following features: multiple lung lesions, tumors adjacent to vulnerable structures, and tumor diameters less than 1.0 cm. Compared to RFA and MWA, LA therapy for lung cancers started relatively late and has been the subject of relatively few studies. Indeed, LA offers advantages such as more precise ablation zone, shorter ablation time and no impedance effect compared with RFA and MWA, making it more effective for tumors adjacent to vulnerable structures (16-18). However, the ablation area of LA is relatively small, which restricts its clinical application. This study focuses primarily on patients with early-stage lung adenocarcinoma who are unwilling or medically unfit to undergo surgical resection. In this study, we improved the LA guiding applicator by designing a waterflood path and injecting 0.5–1 mL saline into the target zone in prior to ablation, and evaluated its efficacy and safety through a pilot study (Figure 1). We present this article in accordance with the MDAR and ARRIVE reporting checklists (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-393/rc).

Figure 1 Schematic diagram of study design. (A) The improved LA needle structure, provided by Jiangxi Medex Technology Co., Ltd. (B) Pre-clinical study in the lung of three pigs. (C) A pilot clinical study in six patients with lung adenocarcinoma manifesting as GGNs. CT, computed tomography; GGN, ground glass nodule; LA, laser ablation.

Methods

Animals and ethical approval

A total of three Yorkshire pigs (from Jurong Kangrong Poultry Co., Ltd., Jurong, China; 3 months old; female; 40–60 kg) were enrolled into this study. All animal experiments were performed under a project license (No. XNM-YX-20240228-01) granted by the regional ethics board of Shanghai Xinova Medical Research Co., Ltd., in compliance with National Institutes of Health guidelines for the care and use of animals.

Patients

The inclusion criteria were: (I) single tumor with diameter <20 mm; (II) patients who refused or were not candidates for surgical resection; and (III) tumors were pathologically confirmed as lung adenocarcinoma before ablation. All patients were collected from Shanghai Pulmonary Hospital. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Shanghai Pulmonary Hospital (No. L20-349Y) and individual consent for this retrospective analysis was waived. A protocol was prepared before the study without registration.

Ablation procedures

LA was performed using the Laser Pro 980 LA system (Jiangxi Medex Technology Co., Ltd., Ganzhou, China), with a continuous-wave output power ranging from 0 to 25 W. Single flexible optical fiber [outer diameter 750 µm, core diameter 550 µm, numerical aperture (NA) 0.22] was used with radial emitting tip. A flexible integrated optical fiber with a wavelength of 980 nm (CFE 0.55-SMA, Hong Kong, China) was used. Computed tomography (CT) scans were employed to identify the needle entry point and measure the depth of insertion. A coaxial needle was used to penetrate the skin, and after passing through the pleura, it was positioned 2 cm away from the designated location. The core of the guiding applicator was withdrawn, and then the laser fiber was introduced only through the tip of the guiding applicator. After that, 0.5 mL of saline was injected through the side port (waterflood path) of the guiding applicator. The guiding applicator was then retracted by 8 mm, while the tip of the laser fiber remained in the original position, allowing ablation to be performed for 60 seconds at 3 W.

MWA was performed using the MTC-3C MWA system (Vison-China Medical Devices R&D Center, Nanjing, China), with a frequency of 2,450±50 MHz and adjustable continuous-wave output power ranging from 0 to 100 W. For the microwave antenna, the effective length ranged from 100 to 180 mm, and the outside diameter was 17 G (MTC-3CA-II19). Detailed ablation procedures were as previously described (18).

Assessment of local response

Animals: whole chest CT scans at 30 min, 1 day, 7 days, and 30 days after ablation were performed. Pathological evaluation was performed at 30 days after ablation (Figure 1B). Three serial 4 µm-thick formalin-fixed paraffin-embedded (FFPE) tissue sections were prepared from each target ablation zone for hematoxylin-eosin (H&E), caspase 3, and caspase 9 staining. Lung cancer patients: follow-up and outcome evaluation were performed according to the expert consensus on TA therapy of pulmonary subsolid nodules (2021 edition) (18) (Figure 1C).

Statistical analysis

The Student’s t-test was used to compare the data between the two groups. All statistical tests were two-sided, and P<0.05 was defined as statistically significant. The analyses were performed using Statistical Package for the Social Sciences (SPSS version 22.0; SPSS Inc., Chicago, IL, USA).

Results

Treatment response of laser and MWA in the pig lung by CT scan

The LA time was 60 seconds with a continuous-energy output power of 3 W; while the MWA time was 240 seconds with a continuous-energy output power of 40 W (Figure 2A). Then, we compared the ablation areas of pre-modified LA (conventional LA), improved LA (saline-enhanced protocol), and MWA in the pig lungs and found that improved LA significantly increased the ablation areas compared to pre-modified LA. However, there was no significant difference between improved LA and MWA at 30 min, 1 day, 7 days, and 30 days post-ablation as observed on CT scans. Representative CT images after ablation are shown in Figure 2B, and quantitative data of the ablation areas by different ablation techniques are presented in Figure 2C-2F.

Figure 2 Comparison of ablation response between pre-modified LA, improved LA and MWA by CT. (A) Parameters of laser and MWA. (B) Representative CT images at 30 min, 1 day, 7 days, and 30 days after ablation. Orange dashed line box means ablated area. (C-F) Quantitative data of (B). ns, not significant (P>0.05); *, P<0.05; **, P<0.01, ***, P<0.001, by the unpaired t-test. CT, computed tomography; LA, laser ablation; MWA, microwave ablation.

Treatment response of laser and MWA in the pig lung by pathological examination

After following up with CT scans for 30 days post-ablation, the lungs of pigs were removed for pathological examination. H&E staining revealed the cavity formation with severe coagulative necrosis of the tissue in both the LA and MWA ablation zones (Figure 3A). The structures of the alveoli around the target ablation area were filled with edematous fluid, and a small infiltrate of inflammatory cells (Figure 3A). A large number of caspase 3 and caspase 9 positive alveolar cells were observed in both the ablation zone and the ablation margin zone (Figure 3A). Figure 3B demonstrated the ablated necrotic areas at gross specimen level. The expression level of caspase 3 was mildly higher in the necrotic region of improve-LA than pre-modified-LA, whereas the expression level of caspase 9 was not significantly different in the necrotic region of both ablation techniques (Figure 3C,3D). These findings indicated that the improved LA could effectively kill cells through the biological thermal effect compared to MWA.

Figure 3 Comparison of ablation response between pre-modified LA, improved LA and MWA by pathological examination. (A) Representative H&E, caspase 3 and caspase 9 staining. (B) Representative ablation on gross specimen. (C,D) Quantitative data of caspase 3 and caspase 9 expression. ns, not significant (P>0.05); *, P<0.05, by the unpaired t-test. H&E, hematoxylin-eosin; LA, laser ablation; MWA, microwave ablation.

Improved LA was safe and effective in the treatment of lung adenocarcinoma manifesting as GGNs

A total of six patients (two men and four women) with eight GGNs underwent improved LA treatment. The mean age of the patients was 62.8 (range, 53 to 76) years. All the GGNs were pathologically diagnosed as lung adenocarcinoma by pre-ablation biopsy. The baseline characteristics of the patients are shown in Table 1. Contrast-enhanced chest CT is the standard method of evaluating technique efficacy at 1 and 6 months post-ablation. Representative CT images of the three GGNs before and after ablation are displayed in Figure 4. There were no ablation-related deaths in all patients. As for complications, only one patient experienced mild pneumothorax, and no cases of hemothorax and infection were observed.

Figure 4 Therapeutic efficacy of improved LA in lung adenocarcinoma manifesting as GGN by CT images. (A) Case 1. (B) Case 2. Orange arrows and boxes showed ablated area. CT, computed tomography; GGN, ground glass nodule; LA, laser ablation.

Discussion

In recent years, local TA therapy has received significant attention for the treatment of primary and metastatic lung cancers. This interest has been associated with progressive advances in energy development, approaches, and technical applications. Compared to RFA, MWA can generate higher intratumoral temperatures and a wider ablation zone, thereby reducing treatment time and improving tumor control rates (19,20). Our decision was based on the following clinical and methodological considerations: first, at Shanghai Pulmonary Hospital, MWA has largely replaced RFA as the standard TA modality for lung tumors. Second, as a pilot study, our primary goal was to benchmark the improved LA against the current institutional standard, MWA. Nonetheless, we acknowledge this as a potential limitation.

While LA started relatively later, it offers some advantages of precision, short duration, and resistance to impedance effects. However, the small area of LA limits its clinical application scenarios, particularly for tumors larger than 1.5 cm.

In this study, we improved the LA guiding applicator by designing a waterflood path and injecting 0.5–1 mL saline into the target zone in prior to ablation. We found that the improved LA significantly increased the effective ablation zone in the pre-clinical studies. Moreover, six patients with eight GGNs (lung adenocarcinoma) received the improved LA, achieving a 100% complete ablation rate. The complications associated with LA are relatively low, which may be related to the fine diameter of the laser fiber. Furthermore, LA can reduce the ablation time to 1 min, which is also effective in reducing complications.

Cryoablation is a relatively new (21) and promising modality with a mechanism of inducing cell death distinct from that of RFA and MWA. In cryoablation, pressurized argon gas is delivered through an orifice in the probe to achieve subzero temperatures (22). Previous studies have demonstrated that temperatures below −40 ℃ are necessary to induce cryogenic destruction and complete cell death (23-25). Unlike TA, cryoablation preserves the collagenous architecture, which is beneficial for tumors located near central airways. Another advantage of cryoablation is the ability to use multiple probes simultaneously during a single session, which shortens procedure time and improves patient experience. Additionally, hypothermic injury induced by cryoablation is generally better tolerated than the hyperthermic injury from RFA and MWA (26). Moore and colleagues reported a 5-year overall survival rate of 67.8%±15.3%, cancer-specific survival rate of 56.6%±16.5%, and 5-year progression-free survival rate of 87.9%±9% in 45 patients with stage I non-small cell lung cancer (NSCLC) following cryoablation (27). However, data directly comparing survival and recurrence rates among contemporary ablation techniques remain limited. Therefore, the superiority of cryoablation over RFA and MWA remains controversial. Large-scale randomized controlled trials are required to clarify this issue.

Conclusions

We improved the LA guiding applicator by designing a waterflood path and injecting 0.5-1 mL saline into the target zone in prior to ablation. We found that the improved LA significantly increased the effective ablation zone in the pre-clinical studies.

Acknowledgments

We thank Dr. Shanshan Yang (Shanghai Xinova Medical Research Co., Ltd.) and members of the Experimental Service Department for animal care duties.

Footnote

Reporting Checklist: The authors have completed the MDAR and ARRIVE reporting checklists. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-393/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-393/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-393/prf

Funding: This work was supported by the National Key Research and Development Program of China (No. 2022YFC2407401) and the Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0511700).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-393/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. All animal experiments were performed under a project license (No. XNM-YX-20240228-01) granted by the regional ethics board of Shanghai Xinova Medical Research Co., Ltd., in compliance with National Institutes of Health guidelines for the care and use of animals. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Shanghai Pulmonary Hospital (No. L20-349Y) 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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