Efficacy of argon–helium cryoablation combined with PD-1 inhibitors in non-small cell lung cancer
DOI:
https://doi.org/10.2340/1651-226X.2025.44215Keywords:
Argon-helium cryoablation, PD-1 inhibitor, Non-small cell lung cancer, Randomized controlled trial, Efficacy, Immune functionAbstract
Background and purpose: This study aimed to evaluate the efficacy and safety of argon–helium cryoablation combined with Programmed Death-1 (PD-1) inhibitors versus PD-1 inhibitors plus chemotherapy in treating non-small cell lung cancer (NSCLC).
Patient/material and methods: In this single-center, open-label, randomized controlled trial, 60 NSCLC patients treated between December 2020 and December 2023 were enrolled. Patients were randomly assigned (1:1) to either a study group (argon–helium cryoablation + PD-1 inhibitor, n = 30) or a control group (PD-1 inhibitor + chemotherapy, n = 30). Allocation was concealed using sequentially numbered, opaque, sealed envelopes (SNOSE). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included short-term efficacy – objective response rate (ORR), disease control rate (DCR) – immune function changes (CD4+, CD8+, CD4+/CD8+), and adverse reactions, assessed after four cycles and during a 1-year follow-up.
Results: ORR and DCR were higher in the study group (ORR: 73.33% vs. 53.33%; DCR: 90.00% vs. 83.33%), though not statistically significant (P > 0.05). Baseline immune parameters were similar. After four cycles, the study group showed statistically significantly higher CD4+ and CD4+/CD8+ ratios, and lower CD8+ levels (all P < 0.001). Adverse reactions were comparable between groups (P > 0.05). At 1-year follow-up, the PFS rate was 63.3% vs. 43.3%. The study group had a statistically significantly better OS (median not reached vs. 10.3 months, P = 0.003) and longer median PFS (9.6 vs. 8.3 months, P = 0.005).
Interpretation: Argon–helium cryoablation combined with PD-1 inhibitors statistically significantly improved OS, PFS and immune function in NSCLC patients, offering a promising alternative to standard therapy.
Downloads
References
Siegel RL, Miller KD. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.
https://doi.org/10.3322/caac.21763 DOI: https://doi.org/10.3322/caac.21763
Yang H, Liu Y, Chen L, Zhao J, Guo M, Zhao X, et al. miRNA-based therapies for lung cancer: opportunities and challenges? Biomolecules. 2023;13(6):877.
https://doi.org/10.3390/biom13060877 DOI: https://doi.org/10.3390/biom13060877
Berg CD, Schiller JH, Boffetta P, Cai J, Connolly C, Kerpel-Fronius A, et al. Air pollution and lung cancer: a review by international association for the study of lung cancer early detection and screening committee. J Thorac Oncol. 2023;18(10):1277–89.
https://doi.org/10.1016/j.jtho.2023.05.024 DOI: https://doi.org/10.1016/j.jtho.2023.05.024
Roelofsz D, Rampon G. Lung cancer in Missouri. MO Med. 2024;121(5):368–72.
Xi Z, Dai R, Ze Y, Jiang X, Liu M, Xu H. Traditional Chinese medicine in lung cancer treatment. Mol Cancer. 2025;24(1):57.
https://doi.org/10.1186/s12943-025-02245-6 DOI: https://doi.org/10.1186/s12943-025-02245-6
Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C, et al. Phase 1b study of sintilimab plus anlotinib as first-line therapy in patients with advanced NSCLC. J Thorac Oncol. 2021;16(4):643–52.
https://doi.org/10.1016/j.jtho.2020.11.026 DOI: https://doi.org/10.1016/j.jtho.2020.11.026
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Non-Small Cell Lung Cancer. Version 3.2024. Published March 15, 2024. [Accessed December 12, 2024] Available from https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450.
Lv Y, Jin Y, Yan Q, Yuan D, Wang Y, Li X, et al. The value of 64-slice spiral CT perfusion imaging in the treatment of liver cancer with argon-helium cryoablation. Oncol Lett. 2016;12(6):4584–8.
https://doi.org/10.3892/ol.2016.5241 DOI: https://doi.org/10.3892/ol.2016.5241
Campbell WA, Makary MS. Advances in image-guided ablation therapies for solid tumors. Cancers. 2024;16(14):2560.
https://doi.org/10.3390/cancers16142560 DOI: https://doi.org/10.3390/cancers16142560
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science (New York, NY). 2018;359(6382):1350–5.
https://doi.org/10.1126/science.aar4060 DOI: https://doi.org/10.1126/science.aar4060
Kim Y, Kim G, Kim S, Cho B, Kim SY, Do EJ, et al. Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. Cell Host Microbe. 2024;32(8):1380–93.e9.
https://doi.org/10.1016/j.chom.2024.06.010 DOI: https://doi.org/10.1016/j.chom.2024.06.010
Yu D, Yang P, Lu X, Huang S, Liu L, Fan X. Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer. Cell Commun Signal. 2023;21(1):169.
https://doi.org/10.1186/s12964-023-01184-3 DOI: https://doi.org/10.1186/s12964-023-01184-3
Ma F, Qi Z, Liao G, Zhao L, Su X, Dong C, et al. Study on PD-1 inhibitor combined with recombinant human endostatin and chemotherapy followed by IMRT in the treatment of advanced NSCLC. Medicine. 2025;104(6):e41306.
https://doi.org/10.1097/MD.0000000000041306 DOI: https://doi.org/10.1097/MD.0000000000041306
Yakkala C, Vaughan D, Kuchi N, Al Tabaa Y, Siah SBB, Hayes C, et al. Cryoablation and immunotherapy: an attractive combination for cancer treatment. J ImmunoTher Cancer. 2019;7(1):337.
Liu SY, Chen Q, Zhou C, Zhang H, Li W, Chen J, et al. Neoadjuvant camrelizumab for non-small cell lung cancer: a retrospective multicenter, real-world study (CTONG2004). Cancer Immunol Immunother. 2023;72(7):2257–65.
https://doi.org/10.1007/s00262-023-03412-8 DOI: https://doi.org/10.1007/s00262-023-03412-8
Feng J, Guiyu D, Xiongwen W. The clinical efficacy of argon-helium knife cryoablation combined with nivolumab in the treatment of advanced non-small cell lung cancer. Cryobiology. 2021;102:92–6.
https://doi.org/10.1016/j.cryobiol.2021.07.007 DOI: https://doi.org/10.1016/j.cryobiol.2021.07.007
Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ (Clinical research ed). 2010;340:c332.
https://doi.org/10.1136/bmj.c332 DOI: https://doi.org/10.1136/bmj.c332
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer (Oxford, England: 1990). 2009;45(2):228–47.
https://doi.org/10.1016/j.ejca.2008.10.026 DOI: https://doi.org/10.1016/j.ejca.2008.10.026
Zhou C, Chen G, Huang Y, Zhou J, Lin L, Feng J, et al. Camrelizumab plus carboplatin and pemetrexed as first-line therapy for advanced non-squamous non-small-cell lung cancer: 5-year outcomes of the CameL randomized phase 3 study. J ImmunoTher Cancer. 2024;12(11):e009240.
https://doi.org/10.1136/jitc-2024-009240 DOI: https://doi.org/10.1136/jitc-2024-009240
Sato Y, Watanabe H, Sone M, Onaya H, Sakamoto N, Osuga K, et al. Tumor response evaluation criteria for HCC (hepatocellular carcinoma) treated using TACE (transcatheter arterial chemoembolization): RECIST (response evaluation criteria in solid tumors) version 1.1 and mRECIST (modified RECIST). Ups J Med Sci. 2013;118(1):16–22.
https://doi.org/10.3109/03009734.2012.729104 DOI: https://doi.org/10.3109/03009734.2012.729104
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Published November 27, 2017. [Accessed December 15, 2024] Available from https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctcae.htm.
Garassino MC, Gadgeel S. Pembrolizumab plus pemetrexed and platinum in nonsquamous non-small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023;41(11):1992–8.
https://doi.org/10.1200/JCO.22.01989 DOI: https://doi.org/10.1200/JCO.22.01989
Alessi JV, Wang X, Elkrief A, Ricciuti B, Li YY, Gupta H, et al. Impact of aneuploidy and chromosome 9p loss on tumor immune microenvironment and immune checkpoint inhibitor efficacy in NSCLC. J Thorac Oncol. 2023;18(11):1524–37.
https://doi.org/10.1016/j.jtho.2023.05.019 DOI: https://doi.org/10.1016/j.jtho.2023.05.019
Hu J, Yuan X, Zhang Y. Efficacy of different ablation methods combined with targeted therapy for non-small cell lung cancer and their effects on serum indexes in patients. Shaanxi Med J. 2024;53(04):527–30.
Niu LZ, Li JL, Zeng JY. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer. World J Gastroenterol. 2013;19(22):3473–80.
https://doi.org/10.3748/wjg.v19.i22.3473 DOI: https://doi.org/10.3748/wjg.v19.i22.3473
Li Y, Feng H, Nie Z. Long-term efficacy and risk factor analysis of percutaneous argon-helium cryoablation for advanced non-small cell lung cancer. J Clin Oncol. 2010;15(4):346–9.
Johnson AM, Boland JM, Wrobel J, Klezcko EK, Weiser-Evans M, Hopp K, et al. Cancer cell-specific major histocompatibility complex II expression as a determinant of the immune infiltrate organization and function in the NSCLC tumor microenvironment. J Thorac Oncol. 2021;16(10):1694–704.
https://doi.org/10.1016/j.jtho.2021.05.004 DOI: https://doi.org/10.1016/j.jtho.2021.05.004
Wang XR, Jiang ZB, Xu C, Meng WY, Liu P, Zhang YZ, et al. Andrographolide suppresses non-small-cell lung cancer progression through induction of autophagy and antitumor immune response. Pharmacol Res. 2022;179:106198.
https://doi.org/10.1016/j.phrs.2022.106198 DOI: https://doi.org/10.1016/j.phrs.2022.106198
Shi L, Lu J, Zhong D, Song M, Liu J, You W, et al. Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy. J ImmunoTher Cancer. 2023;11(1):e005902.
https://doi.org/10.1136/jitc-2022-005902 DOI: https://doi.org/10.1136/jitc-2022-005902
Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545(7652):60–5.
https://doi.org/10.1038/nature22079 DOI: https://doi.org/10.1038/nature22079
Zhu X, Sun L, Song N, He W, Xie B, Hu J, et al. Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate002): an open-label, single-arm, phase 2 trial. BMC Med. 2022;20(1):493.
https://doi.org/10.1186/s12916-022-02696-4 DOI: https://doi.org/10.1186/s12916-022-02696-4
Zhang Y, Zhu T, Wang Q, Wang J, Chen X. Effects of PD-1 inhibitor combined with anti-angiogenic drugs on efficacy and immune function of non-small cell lung cancer. Am J Transl Res. 2022;14(11):8225–33.
Li L, Liu C, Cao S. Clinical significance and impact on immune function of cryoablation in lung cancer patients. Chin J Cancer Prev Treat. 2021;28(16):1231–5.
Yin C, Zou GR, He Y, Li J, Yan HW, Su Z, et al. Efficiency and toxicity of nab-paclitaxel and camrelizumab in the second or above line treatment of advanced non-small cell lung cancer: a retrospective cohort study. J Thorac Dis. 2023;15(4):1838–47.
https://doi.org/10.21037/jtd-23-387 DOI: https://doi.org/10.21037/jtd-23-387
Chen J, Deng A, Li X. Effect of argon-helium knife cryoablation combined with TP chemotherapy regimen on serum tumor marker levels and prognosis in lung cancer. Chin Med Equip. 2020;17(09):94–8.
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Zheng Zheng, Bo Tian, Yonghui An, Wei Wang, Miaomiao Zhang, Wenhua Ma, Ying Guo, Yao Fan, Na Li

This work is licensed under a Creative Commons Attribution 4.0 International License.
