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Background: Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet., Methods: An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed., Results: 36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months., Conclusion: Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases., Trial Registration Number: ChiCTR2200061544., Competing Interests: Competing interests: Dr Chi Yang is a full-time employee of AccuTarget MediPharma (Shanghai) Co., Ltd. Dr Jiayuan Sun serves on the advisory abroad and receives consultant fees from AccuTarget MediPharma (Shanghai) Co., Ltd. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC., Methods: We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP ( Kras G12D/+ , Tp53 -/- ) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC., Results: We found that cryoablation significantly increased circulating CD8 + T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8 + T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8 + T cell infiltration in patients with unresectable NSCLC., Conclusions: Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The purpose of this study was to evaluate the feasibility and safety of transbronchial cryoablation with a novel flexible cryoprobe using nitrogen as the refrigerant in an in vivo porcine model of lung parenchyma., Materials and Methods: A novel flexible cryoprobe using nitrogen as the refrigerant was used for transbronchial cryoablation of lung parenchyma in six normal female pigs. The cryoprobe was delivered to the distal bronchus in the bilateral porcine lungs via the bronchoscopic working channel under virtual bronchoscopy guidance. The position was confirmed with real-time computed tomography (CT). The whole procedure included two freeze-thaw cycles (15 min and 2 min, respectively). CT images were obtained during cryoablation and at 24 h, one week, two weeks and four weeks after the treatment to assess the effectiveness and safety of the procedure. Ablation zone tissue samples were obtained at 24 h and four weeks after the cryoablation for further histopathological analysis., Results: All ablation procedures (12/12; 100%) were performed successfully. No major complications occurred during the procedure or the observation period. The ablation zones were clearly depicted on CT with a maximal ablation zone volume at 24 h (21.88 ± 12.61 [SD] cm 3 ) compared to 3.64 ± 2.06 (SD) cm 3 and 10.73 ± 3.84 (SD) cm 3 at the end of the 1st and 2nd freeze-thaw cycles, respectively (P < 0.001). Histopathological analysis revealed that a coagulative necrotic zone was formed along the target bronchus, with obvious vascular occlusion and hemorrhage 24 h after treatment. The lesions gradually formed fibrosis after four weeks., Conclusion: The novel flexible bronchoscopy-guided cryoablation is a feasible, safe and effective modality in an in vivo porcine model of peripheral normal lung parenchyma, suggesting potential capabilities for the treatment of peripheral lung cancer in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2021 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite advances in technology, the bronchoscopic diagnosis of parenchymal pulmonary lesions (PPLs) remains difficult to achieve. Transbronchial lung cryobiopsy (TLCB) offers the potential for larger samples with improved diagnostic yield; however, a paucity of data exists describing its safety and usefulness for the diagnosis of PPL., Research Question: What is the safety profile of TLCB for PPL?, Study Design and Methods: An observational, retrospective, multicenter cohort study enrolled patients without endobronchial disease undergoing TLCB of PPL from 2015 through 2019. All procedures were performed using both rigid and flexible bronchoscopy with a flexible cryoprobe. Complication rates, including bleeding and pneumothorax rates, were collected. Bleeding was graded on a scale from 0 (trace) to 4 (requiring surgical intervention) with a grade of ≥ 3 considered clinically significant. Pneumothorax, tube thoracostomy placement, diagnostic yield, and need for subsequent interventions were recorded., Results: One thousand twenty-four patients underwent TLCB. One hundred eighty-eight patients (18%) experienced bleeding; in 36 patients (3.5%), the bleeding was clinically significant. Sixty-eight patients (6.6%) demonstrated a pneumothorax and 64 patients (6.3%) required drainage with tube thoracostomy. All chest drains were removed within 4 days, and no cases of prolonged air leak occurred. A definitive diagnosis was achieved in 932 patients (91%). Adenocarcinoma (46%) and metastatic disease (21%) were the most common diagnoses., Interpretation: TLCB showed an acceptable safety profile and diagnostic yield for the evaluation of PPL in this large retrospective cohort. Prospective clinical trials are underway to validate these findings further., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous cryoablation has been used for the treatment of lung cancer and has been shown to be safe and effective. However, some lung cancer lesions cannot be reached by percutaneous puncture; using bronchoscopy cryoablation is necessary in these cases., Purposes: To examine the efficiency and security of a flexible cryoprobe, we measured the size and temperature distribution of the frozen area (ice ball) in ex vivo pig lung and liver and the temperature of the bronchoscope., Methods: We evaluated flexible cryoprobe cryoablation using a bronchoscope in ex vivo pig lung and a flexible cryoprobe alone in ex vivo pig liver. Seven temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.3, 0.6, 0.9, 1.2, 1.5, and 1.8 cm from the cryoprobe. Two temperature sensors were positioned at the surface of the bronchoscope. The ex vivo pig lung and liver were perfused with 37°C saline and the former was inflated using a ventilator to simulate in vivo lung conditions. The whole operation is usually 2-3 freezing cycles., Results: In ex vivo pig liver, probes made ice balls of 33.2 ± 0.2 mm in diameter. In ex vivo pig lung, probes made ice balls of 35.1 ± 1.7 mm in diameter. The temperature at the surface of the bronchoscope at distances of 1 and 10 cm from the cryoprobe reached 21.1 ± 0.1 and 10.5 ± 0.2°C., Conclusion: A flexible cryoprobe using a bronchoscope in ex vivo pig lung and liver was a sufficiently safe treatment method., (© 2019 S. Karger AG, Basel.)

Background: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. Summary: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. Key Messages: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy. [ABSTRACT FROM AUTHOR]

Introduction: Cryobiopsy (CB) using a 1.1-mm cryoprobe under fluoroscopic guidance is feasible and safe for diagnosis of ground glass opacity (GGO) lesions. However, the efficacy of CB combined with cone-beam CT (CBCT) for GGO-predominant pulmonary nodules remains elusive. Methods: We retrospectively studied patients who underwent CB combined with conventional biopsy under CBCT guidance for GGO-predominant pulmonary nodules with a consolidation-to-tumour ratio <50.0%. Results: A total of 32 patients with GGO-predominant pulmonary nodules were enrolled: 17 pure GGOs and 15 mixed GGOs. The mean lesion diameter was 15.81 ± 5.52 mm and the overall diagnostic yield was 71.9%. Seven lesions were diagnosed by CB alone, which increased the diagnostic outcomes by 21.9%. Diagnostic yields for CB, forceps biopsy (FB), brushing, and guide sheath flushing were 65.6%, 46.9%, 15.6%, and 14.3%, respectively. Univariate analysis revealed that positive computed tomography (CT) bronchus sign (p = 0.035), positive CBCT sign (p < 0.01), and CB-first biopsy sequence (p = 0.036) were significant predictive factors for higher diagnostic yield. Specimens obtained by CB had larger mean sample size (p < 0.01), lower blood cell area (p < 0.01), and fewer crush artefacts (p < 0.01) than specimens from FB. No severe bleeding or other complications occurred. Conclusion: CB using a 1.1-mm cryoprobe under CBCT guidance increased diagnostic yield for GGO-predominant pulmonary nodules based on conventional biopsy. Further, it provided larger and nearly intact samples compared with forceps. [ABSTRACT FROM AUTHOR]