Liquid nitrogen spray cryotherapy (SCT) in central airway disease: a multicenter prospective registry

Introduction

Spray cryotherapy (SCT) was initially developed for endoscopic mucosal ablation in the esophagus in 1999 (1). Over the following decade, this technology transitioned to airway applications by pulmonologists and thoracic surgeons. In 2012, a multi-institutional retrospective review of selected airway use of the “G2” SCT device reported promising treatment results and unique operating characteristics but also a high complication rate (2). Later that year, a redesigned SCT device was introduced in the U.S. and received 510K FDA clearance for use in surgical procedures including bronchoscopy. This improved system (trūFreeze Spray Cryotherapy, STERIS) featured novel technology providing uniform liquid nitrogen spray delivery and adjustable flow rates to enhance safety and efficacy (3). In 2013, a prospective multi-institutional registry using the trūFreeze system was formed to collect and evaluate longitudinal efficacy, safety, and patient selection data for both esophageal and pulmonary disease. While multiple retrospective reports of SCT use in benign and malignant pulmonary diseases using the trūFreeze system exist (4-8), this study presents the only prospective data available on SCT use in a mixed benign/malignant cohort with comprehensive follow-up for up to 5 years. The esophageal indications and techniques for SCT are different enough that they have been reported in a separate publication (9). We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1634/rc).

Methods

Patients undergoing SCT were enrolled in this prospective observational registry at Boston Medical Center (BMC), New York University Langone (NYU) Department of Cardiothoracic Surgery, University of Maryland Medical Center (UMMC), and Walter Reed National Medical Center (WRNMMC) for up to 5-year follow-up (2013–2021). The BMC, NYU, UMMC, and WRNMMC Institutional Review Boards approved this study (Nos. H-33672; i14-00196; HCR-HP-00055345; 389070). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Informed consent was obtained from all individual participants included in the study. Data focusing on patient safety, diseases treated, dosimetry and selected efficacy measures were collected in a standardized electronic case report form (see Appendix 1) and stored and monitored in a central database through the independent data coordinating center at University of North Carolina at Chapel Hill. The study is registered at ClinicalTrials.gov (NCT01802203). Consenting patients treated using the trūFreeze SCT device for the removal of unwanted tissue, such as malignant or pre-malignant conditions in the central airways and pleura were enrolled in the study and data for all subject visits and procedures were captured longitudinally in this prospective, multi-center registry with active monitoring (2013–2021). Exclusion criteria were pregnancy, tracheoesophageal fistula, bronchopleural fistula, current untreated pneumothorax, clinically significant hypoxia refractory to supplemental oxygen therapy, and any patients who could not tolerate a bronchoscopy. Due to the planned longevity of the trial, enrollment was monitored closely along with site support, resources and funding to limit enrollment to allow for the potential 5-year follow-up for each participant. All of the treating investigators went through the initial FDA approved training on the use of the device and all were experienced interventional pulmonologists, thoracic surgeons or otolaryngologists who regularly treated complex airway diseases bronchoscopically. SCT dosimetry for each location was recorded as the setting used (low or normal flow), the time in seconds of visible freezing and the number of freeze/thaw cycles delivered to the target during the procedure. Total procedure time was not captured in the registry database only the time spent using SCT. Target tissue location and standardized descriptors at each SCT treatment site were recorded for all procedures. Tissue descriptors treated included friable, infiltrating tumor, necrotic tissue, along with assessment of extrinsic compression versus endobronchial tumor obstruction as well as bleeding during the procedure. All devices used during each case in addition to SCT were recorded as well as any procedures that did not use SCT during the study period of up to 5 years from patient enrollment. Airway obstruction and stenosis were assessed by the bronchoscopist endoscopically both pre and post procedure using a quartile grading system (1 = <25%, 2 = 25–50%, 3 = 51–75%, 4 = >75%) (4,7,10). Hemostasis success was prospectively defined as complete cessation of active bleeding on visual inspection by the bronchoscopist without need for additional hemostatic interventions beyond SCT (complete success) or reduced but not completely controlled bleeding requiring adjunctive hemostatic measures (partial success). Assessment was based on the treating bronchoscopist’s real-time procedural evaluation.

Statistical analysis

Descriptive analysis was performed using SAS version 9.4. Missing data were assessed for patterns and frequency, with complete case analysis performed for all reported outcomes. No imputation methods were employed given the descriptive nature of this registry study. Continuous variables are reported as median with interquartile range (IQR) or mean with standard deviation as appropriate. Categorical variables are reported as frequencies and percentages without unnecessary decimal points for sample sizes less than 100. Retreatment intervals were calculated as the number of days between consecutive SCT procedures for patients undergoing multiple treatments.

Results

A total of 64 patients from 4 participating institutions were enrolled in the registry. All patients received at least one SCT treatment, with 114 total SCT procedures performed and 472 SCT freeze/thaw cycles delivered in total, with 464 to the large airways and 8 to the parietal pleura (in patient with metastatic pleural disease for palliative pain control and pleurodesis). The location of SCT used in the large airways for each spray delivered in the study was recorded to assess for practice patterns, safety and future application of study findings. For the study and case report forms, the large airway was divided into 14 areas, and each spray location was documented by the bronchoscopist performing the procedure (Table 1, Figure 1). SCT freeze time per spray of each freeze cycle ranged from 5 to 10 seconds with 86% of sprays being 5 seconds in duration. During each procedure, the number of cycles of SCT used varied from 1–8 cycles with 94% using 1–4 cycles per location. Description of patients in the registry is listed in Table 2. with additional comorbidities and range of concurrent cancer treatments for the malignant cohort in Tables S1,S2. Patient demographics showed a predominance of females (approximately 58%) and primarily Caucasian patients although 19% were Black and 5% were Hispanic. Airway disease included 47 (73%) malignant and 17 (27%) benign etiologies. Rigid bronchoscopy was used in approximately half (48%) of cases. When an endotracheal tube (ETT) was employed, only 8.0 mm or greater were used with an 8.5 or 9.0 mm ETT used 90% of the time. Laryngeal mask airway was not used in this registry.

Figure 1 Tracheobronchial tree thermal map of freezing frequency by location. Color scale represents number of freezing treatments delivered at each location within the 14 regions (described in Table 1) of the airway with the highest density of freezing designated in dark blue as depicted on the color scale bar.

In the malignant disease cohort, 66% were advanced stage or metastatic disease. Of the 47 patients with cancer, 13 (28%) completed the 5-year follow-up period and 34 (72%) died during the study period. The median observed follow-up for the malignant cohort was 520 days (IQR, 153–1,818 days). For the benign cohort, 14 patients (82%) completed the 5-year follow-up, 2 (12%) died during follow-up, and 1 (6%) was lost to follow-up at 1,623 days. The median observed follow-up for the benign cohort was 1,803 days (IQR, 1,769–1,832 days). For the subgroup of lung cancer patients (N=25), 20 had advanced stage disease with an observed follow up of 690 days, and 3 of the advanced stage lung cancer patients survived to end of study with a mean follow up of 1,850 days. SCT was used in treating 14 different cancer types (see Figure 2) with the majority identified as lung cancer (30% squamous cell, 23% adenocarcinoma, 4% small cell) followed by renal cell carcinoma (11%). Within this cohort, 29 (36%) had more than one SCT procedure (8 patients had 2 procedures, 5 with 3 procedures, 2 with 4 procedures, 1 with 5 procedures and one patient receiving a total of 7 SCT treatments over multiple years). For patients who underwent multiple SCT procedures, the median retreatment interval between consecutive procedures was 42 days (IQR, 27–93 days) in the malignant cohort and 116 days (IQR, 63–279 days) in the benign cohort. SCT for airway tumor was used exclusively in the large airways with 25% in left main bronchus, 20% right main bronchus, 17% right bronchus intermedius and 13% in the distal trachea. The most distal areas treated were the left and right lower lobe orifices. Malignant tissue descriptors of SCT target tissue were most commonly friable tissue, infiltrating tumor and necrotic tumor (with 32%, 39%, 18%, respectively). In 10% of cases, SCT was used to treat tissue adjacent to silicone and silicone covered stents. Overall obstruction/stenosis grade change in the combined malignant and benign cohort by procedure (N=95) results showed 59 (62%) improved by one or more grades, 35 (37%) unchanged and 1 (1%) with increased grade. In the malignant group, an improvement in airway obstruction of one or greater grade (quartile decrease) on the post procedure assessment was seen in 23 of the cases (53%) at initial bronchoscopy and none had an increase in obstruction grade. In patients who underwent a second bronchoscopy with SCT, 9 cases (75%) had additional airway improvement, and all had maintained the previous airway patency. In the benign cohort, 14 patients completed the study with 5-year follow-up, 1 patient lost to follow up at 1,623 days and 2 died (471 days and 1,349 days of follow up). In this group, 79% of SCT was performed in the subglottic region and upper third of the trachea (52%/27% respectively). Stenosis and friable were most often used to describe treatment tissue in the benign disease cohort (68%/60% of cases respectively). The same quartile assessment of degree of stenosis described above was used for benign airway disease (4,7,10). In our study, 13 (81%) had at least one quartile improvement with the first procedure. Only 3 patients with benign disease required more than 2 procedures with SCT over the study period with a max of 4 procedures demonstrating excellent treatment durability with low overall procedure burden. The majority of benign patients (14/17, 82%) achieved sustained benefit with 1–2 treatments total. All patients with stenosis in the benign cohort had less than 25% stenosis by their last procedure.

Figure 2 Distribution of malignancies treated with SCT (N=47) stratified by disease type and survival status. (A) Primary lung cancer cases (N=27, 57%) by histologic type. (B) Metastatic disease (N=20, 43%) by primary site. SCT, spray cryotherapy.

Concurrent bronchoscopic interventions and tools were commonly employed as part of comprehensive airway management (Table S3). Balloon dilation was the most common concurrent intervention (50% of procedures), probe cryotherapy was used in 16% of cases, and airway stents in 14% of procedures. SCT was reported by the bronchoscopist as specifically being used to control endobronchial bleeding in the airways (achieve hemostasis) during the procedure in 34 (30%) cases and reported to have complete success in 31 (91%) and partial success in 3 (9%) of these cases. Two adverse events meeting protocol-defined reportable event criteria occurred during the study period (1.8% of 114 procedures). One asymptomatic mild pneumothorax occurred in a 43-year-old female ICU patient with stage IIIB lung cancer during a complex procedure requiring stent removal for proximal and distal obstruction of a hybrid silicone nitinol stent in the proximal to distal left main bronchus with friable tissue obstructing at the main carina. Rigid bronchoscope (11 mm) and jet ventilation was used for the procedure, and a total of 2 sprays (5 seconds each) were performed at the proximal left main and main carina with the jet ventilation held and 11 mm rigid scope open proximally for maximal passive ventilation during the spray. After the initial stent removal, a larger stent was placed to maintain patency of the left main bronchus. The pneumothorax was detected on routine post-procedural chest radiography, localized with point-of-care ultrasound, and successfully managed with catheter aspiration using a 5 French catheter. Given the limited SCT exposure, optimal passive ventilation through the 11 mm open rigid bronchoscope, and extensive mechanical trauma from stent extraction, the observed mechanical airway injury was thought to be the more likely etiology. One death occurred 6 days post-procedure in a patient with advanced malignancy; the death was due to airway obstruction from residual tumor dislodged during a subsequent medical intervention unrelated to SCT, and independent investigator review confirmed the death was unrelated to the SCT device or procedure. Per protocol criteria, deaths from expected disease progression are not classified as device-related adverse events; however, this death was appropriately captured in the registry given the temporal association with the SCT procedure, though causality assessment clearly indicates the event was unrelated to the device or procedure. No other events meeting protocol-defined reportable event criteria occurred, including no cases of pneumomediastinum, significant hemorrhage requiring intervention beyond routine hemostatic measures, hemoptysis, arrhythmia, or air embolism attributable to SCT.

In the malignant cohort, 13 patients (28%) completed 5-year follow-up and 34 patients died during the study period; there were no patients lost to follow-up in the malignant cohort. In the benign cohort, 14 patients (82%) completed the 5-year study follow-up, 1 patient (6%) was lost to follow-up at 1,623 days, and 2 patients (12%) died during follow-up (at 471 and 1,349 days). Overall, 1 of 64 patients (1.6%) was lost to follow-up.

Discussion

This prospective registry provides detailed longitudinal data on device use and patient outcomes for this novel device and technology. SCT is the only bronchoscopic tool that has the capability to deliver flash freezing temperatures with the direct application of liquid nitrogen (−196 ℃) in the airways. Proper management of the nitrogen gas formed with each spray as a result from the phase change of liquid nitrogen to nitrogen gas (1:700×) is essential to the safe use of this technology (11). The technique of SCT delivery used in this registry prioritizes ensuring adequate passive egress pathways and limiting the time of continuous freezing (liquid nitrogen delivery which determines volume of gas formed) before and during each spray. As per the instructions for use, prior to each spray, passive egress for the nitrogen gas was ensured with disconnection of the ETT and deflation of the ETT cuff or if a rigid bronchoscope was used, stopping ventilation (jet or conventional) and allowing maximal open proximal rigid scope egress as well as visually ensuring adequate egress. With passive egress assured and bronchoscope and catheter in position for SCT, the foot pedal is pressed and held to start flow through the catheter. The 7 Fr straight end delivery SCT catheter initially delivers a mixture of nitrogen gas and liquid nitrogen which becomes pure liquid nitrogen as the spray continues. The time for this transition of gas to liquid nitrogen delivery depends on the flow rate (normal vs. low) and can range from approximately 10–20 seconds for normal flow (25 W) to 30–60 seconds for low flow (12.5 W). Freeze time was measured from the start of visible frosting covering more than 50% of the target surface area. Typically, 1–2 cm was normally targeted for each spray to ensure adequate SCT delivery to the area. Thawing time varied with spray location, tissue type and adjacent vascular structures that affect tissue temperature but at a minimum was 1–3 minutes to wash out residual nitrogen gas with oxygen ventilation. The lower flow rate produces nitrogen gas at half the rate, increasing safe egress time which is advantageous for more distal locations or areas where nitrogen gas must travel further or through narrower areas to exit. Low flow also creates a smaller circular spray pattern offering more precision and localized delivery when desired. Typically, the freezing or frosting time was increased with the low flow (mostly to 10 seconds) to deliver dosing comparable to normal flow. Another distinctive characteristic of SCT is its ability to be used safely in high oxygen concentrations within the lung in contrast to all other heat/thermal bronchoscopic tools which require oxygen concentrations to be less than 40% to avoid combustion and catastrophic airway fire. This feature of SCT also allows for safe use near combustible and flammable plastics in the airway such as silicone stents and endotracheal tubes. SCT alone would not be expected to immediately provide malignant obstruction relief. In the malignant cohort, SCT was commonly used with debulking tools, delivering repeated applications to friable tumor, tumor base and infiltrating tumor. The potential beneficial immediate effects of tissue devitalization, micro thrombosis and vasoconstriction of the tumor and adjacent tissue with SCT may play an important role in the intraprocedural airway diameter improvements. The more expected delayed effects of freezing tissue may have contributed to the larger improvement in airway obstruction and persistence of airway patency on subsequent procedures. Treatment of tissue adjacent to silicone or hybrid/metallic stents (10% of cases) resulted in no adverse events to the patients or stents. This finding correlates well with a recently published study on the effects of SCT on both silicone and metallic stents which concluded that SCT does not adversely affect the stent or its ability to function properly (12). A wide range of tumor types within the airways were treated safely with SCT (see Figure 2), although the majority were primary lung cancers. In the treatment of benign disease, SCT was most used in combination with balloon dilation, like previously published retrospective studies on SCT in subglottic stenosis (2-5,7). The most common location of benign disease treatment was the subglottic and upper trachea, and these benign cases represent the majority of upper tracheal SCT sprays shown on the combined freeze map in Figure 1. Demographic differences between cohorts reflect underlying disease epidemiology. The benign cohort’s female predominance (94%), higher body mass index (BMI) (29.7 vs. 24.1 kg/m²) are consistent with idiopathic subglottic stenosis, which disproportionately affects middle-aged women. The malignant cohort exhibited typical thoracic malignancy demographics with balanced gender distribution and lower BMI. In our prospective cohort, the finding of improved airway diameter with a low rate (most 1–2) of retreatments over the 5-year study period is promising and consistent with overall findings from the previous retrospective studies cited (2-5,7). Bronchoscopists reported their intention to use SCT for its hemostatic properties and non-contact delivery in 30% of cases and reported it to be effective in achieving complete hemostasis 91% of the time. The use of iced saline for hemostasis in bronchoscopy is well established and the extension of a much colder liquid (up to −196 ℃), achieving this effect is conceptually familiar. Arterial bleeding or massive bleeding could still be a challenge as SCT is time limited or continuous spray delivery due to the requirement for passive egress of the nitrogen gas formed during phase change from liquid to gas at a ratio of 1:700.

While the study design captured longitudinal prospective data on a wide range of malignant and benign diseases and practice patterns for use of this device, this study has several limitations. As an observational registry without a control arm, causal inferences regarding efficacy cannot be made. This pragmatic registry design prioritized comprehensive safety monitoring and procedural characterization rather than standardized functional assessments. Collection of objective functional outcomes (spirometry, validated symptom scores, 6-minute walk tests) would require uniform longitudinal protocols and equipment across sites, more appropriate for controlled trials than real-world registries. Although the diverse range of malignancies treated with SCT in this cohort can be considered a strength in the data, the small sample sizes for some of the tumor types make generalization impossible. In the benign cohort, the registry only reported single cases of tracheal amyloidosis, sarcoidosis, Wegener’s granulomatosis or granulomatosis with polyangiitis (GPA), granulation tissue, post tracheostomy stenosis with two patients listed with a differential of Wegener’s versus granulation tissue and the second with idiopathic versus Wegener’s versus amyloid. The remainder were assumed to be idiopathic as the field was not mandatory and often not known at time of the procedure, and the majority of benign upper tracheal stenosis are idiopathic. This is a limitation of the registry and general clinical practice of benign airway stenosis. Alternative bronchoscopic modalities including mechanical debulking, argon plasma coagulation (APC), electrocautery, laser therapy, balloon dilation, probe cryotherapy and stents are commonly used in interventional pulmonology, often in multimodal combinations tailored to individual patient needs and tissue characteristics. As detailed in Table S3, concurrent interventions were employed in the majority of procedures across both cohorts. This multimodal approach reflects standard practice in complex airway disease, where individualized treatment strategies combine multiple modalities to achieve optimal outcomes. Although procedure duration is often reported in bronchoscopic studies, total procedure duration (start to end time) was not systematically recorded in the registry database. The registry focused on SCT-specific parameters including freeze time per spray, number of freeze/thaw cycles, and thaw time, which were considered most relevant for safety protocol development and reproducibility of the technique.

The 2025 American College of Chest Physicians clinical practice guideline for management of central airway obstruction (CAO) provides important context for evaluating evidence standards in interventional pulmonology. The guideline panel concluded that “the management of CAO is supported by limited high-quality evidence amidst significant heterogeneity of patients and disorders” and that “the overall certainty of evidence was very low”, resulting in all ten graded recommendations being conditional rather than strong (13). This guideline explicitly acknowledges that “multi-modality therapeutic options” represent standard practice and note “ethical challenges for designing a randomized controlled trial withholding therapeutic bronchoscopy from symptomatic patients” (13). For malignant CAO, even the most widely used and longest-established techniques lack comparative prospective data. APC, one of the most commonly employed thermal ablation modalities, has no prospective comparative trials despite decades of clinical use and inclusion in the 2025 CHEST guidelines for CAO (13-16). Nd:YAG laser therapy, with over 40 years of worldwide experience and extensive published literature, has only one prospective randomized trial, which compared laser alone to laser combined with brachytherapy rather than comparing laser to alternative modalities or no treatment (17,18). Even mechanical tumor debulking itself—arguably the most fundamental interventional bronchoscopy technique—relies primarily on prospective registry or single-arm observational data. The CHEST CAO guidelines (13) cite the AQuIRE registry of 947 patients undergoing rigid bronchoscopy as primary supporting evidence, an observational registry without randomization to alternative strategies (19). Microdebrider bronchoscopy, despite over 20 years of clinical use, has only one prospective case series with 23 patients (20), one case report (21) and one retrospective study with 51 patients and no comparison group (22), with authors acknowledging that while “prospective trials are required”, there exists fundamental “difficulty of designing blinded randomized controlled trials in this critically ill population” (20,21). For benign airway stenosis, the 2025 CHEST guidelines acknowledge “very low” certainty of evidence for airway dilation approaches (13). Balloon dilation has reported recurrence rates of 12.9–51.6% at 1–3 years (23,24), but interpretation is complicated by concurrent use of laser resection (53% of procedures) and adjuvants such as mitomycin C (66%) (24). Notably, mitomycin C has prospective RCT data demonstrating equivalence to placebo (25,26), yet it remains a common adjunct therapy in clinical practice at many institutions. This multimodal approach reflects real-world practice patterns but creates methodologic challenges for establishing evidence-based treatment algorithms, as explicitly recognized by the 2025 CHEST guidelines (13) which recommend individualized management based on stenosis characteristics and operator expertise.

Two ongoing randomized trials are investigating SCT for benign airway stenosis. The CryoStasis trial (NCT04996173) (27) compares SCT plus standard of care (thermal/laser therapy, balloon dilation, steroids, and mitomycin C) versus standard of care alone, with projected completion in 2027. The Cryo-BAS trial (NCT06761170) (28) compares SCT plus balloon dilation versus steroid injection plus radial cuts plus balloon dilation, also with projected completion in 2027. These trial designs illustrate the methodologic complexity inherent to interventional pulmonology research: neither trial tests SCT as monotherapy because the control arms themselves utilize combinations of interventions (balloon dilation, steroids, radial incisions, thermal therapy) that also lack head-to-head comparative evidence from prior randomized trials. This necessarily limits the ability to attribute outcomes to any single modality, even within prospective randomized studies. The trials therefore reflect the clinical reality that management of complex airway stenosis typically requires multiple complementary techniques, and that establishing the independent contribution of individual modalities remains challenging when the comparative effectiveness of control arm interventions has not been rigorously established. Results from these studies will nonetheless provide important prospective data regarding the role of SCT within multimodal treatment strategies.

The safety profile observed in our prospective registry represents a marked improvement over the 2012 multi-institutional retrospective review by Finley et al. (2) using the G2 SCT device which reported concerning complication rates including 19% overall complications, 9% grade ≥3 complications, and 4% mortality. Specific adverse events in that study included pneumothorax, pneumomediastinum, respiratory failure, and deaths related to the procedure. In contrast, our prospective registry of the trūFreeze system demonstrated only 2 reportable events among 114 procedures (1.8%), with no SCT-related deaths and one minor pneumothorax unlikely related to the procedure. This represents an approximate 95% reduction in serious adverse events compared to the 2012 G2 device study, which we attribute to the improved device design with adjustable flow rates and a consistent passive nitrogen gas venting protocol. Additionally, in the malignant cohort, the majority of patients had received or were receiving systemic cancer therapies concurrently or prior to SCT treatment. Specifically, 59% had received chemotherapy, 37% radiation therapy, 43% prior surgical resection, 10% metastatectomy, 2% immunotherapy (see Table S2). Despite these comorbidities and prior and concurrent therapies, the adverse event rate remained very low, demonstrating the safety of SCT even in complex, high-risk patients.

This longitudinal prospective cohort spanning up to 5 years of clinical follow up in patients treated with the trūFreeze system demonstrated minimal adverse events without long-term sequelae or complications to suggest permanent damage to cartilage or the epithelium. Novel multimodal precision cancer treatments are rapidly extending the lives of patients with advanced malignancies like lung cancer for years with episodes of recurrence as the cancer develops resistance to their most current treatments. For those with airway involvement, measured endobronchial management with tools that minimize collateral damage to normal tissue (stricture, fistula, perforation, scarring, etc.) and promote a normal healing response may become more critical. SCT also has the advantage of preserving biopsy specimen quality even in treated areas especially when repeat biopsy is necessary to understand new mutations and identify possible new targets for continued systemic therapy. Overall, the close attention to dosimetry, practice patterns and safety in this prospective registry study provides a useful framework for current SCT clinical use and further study of this novel flash-freezing, non-contact bronchoscopic tool.

Data integrity and independence were maintained through several mechanisms. The University of North Carolina at Chapel Hill served as an independent data coordinating center, with site investigators entering data prospectively without involvement of the study sponsor in data collection or entry. Statistical analysis was performed independently by a biostatistician at the Center for Gastrointestinal Biology and Disease at UNC who had no financial relationship with the device manufacturer. While several authors have disclosed financial relationships with the device manufacturer or related technology, the study design with independent data management and analysis provides safeguards against bias in data collection and interpretation. As with any industry-sponsored registry, readers should interpret results within the context of the observational study design and the potential for selection bias in patient enrollment and procedure selection.

Conclusions

This analysis of a longitudinal prospective cohort treated with the trūFreeze system demonstrates that SCT can be safely applied in central airways when following the described passive ventilation technique and dosimetry approach. Treatment outcomes across various benign and malignant airway diseases are consistent with previously published retrospective studies of SCT, suggesting the potential utility of SCT’s unique flash freezing capability as a bronchoscopic tool for use in the clinical management of diseases of the central airways, although controlled studies would clarify the optimal role for SCT in specific airway conditions.

Acknowledgments

Special acknowledgement to Chelsea Anderson, PhD, Biostatistician at the Center for Gastrointestinal Biology and Disease, University of North Carolina, for statistical and analytic support for this manuscript. Special thanks to Patrick Shuster, RN, Pulmonary Medicine, Walter Reed National Military Medical Center, Bethesda, MD, for manuscript figure design.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1634/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1634/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1634/prf

Funding: This study was initially sponsored by CSA Medical Inc. until the 2019 acquisition of the trūFreeze assets by U.S. Endoscopy Group Inc. (subsidiary of STERIS), which is the current study sponsor.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1634/coif). R.F.B. received research grant support from U.S. Endoscopy Group, Inc., CSA Medical Inc., and consulting fees/travel from CSA Medical Inc. S.C.P. received consulting fees/travel from CSA Medical Inc. C.S.B. received consulting fees/travel from STERIS and U.S. Endoscopy Group, Inc. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, U.S. Department of Defense (DoD), or any component U.S. agency. The views expressed in this article are those of the author and do not reflect the official policy of the U.S. Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. The other 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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The Boston Medical Center, New York University Langone, University of Maryland Medical Center, and Walter Reed National Medical Center Institutional Review Boards approved this study (Nos. H-33672; i14-00196; HCR-HP-00055345; 389070). Informed consent was obtained from all individual participants included in the study.

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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