{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:31:58Z","timestamp":1785540718010,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Research Council of Lithuania","doi-asserted-by":"publisher","award":["S-MIP-23-97"],"award-info":[{"award-number":["S-MIP-23-97"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Cryotherapy is used for local tissue destruction through rapid freeze\u2013thaw cycles. It induces cancer cell necrosis followed by inflammation in the treated tumor microenvironment, and it stimulates systemic adaptive immunity. Combining cryotherapy with immunotherapy may provide a sustained immune response by preventing T cell exhaustion. Methods: Fifty-five patients with metastatic non-small cell lung cancer who had received no prior treatment were randomized into two groups in a 1:1 ratio: the bronchoscopic cryotherapy group or the control group. Patients received up to four cycles of pembrolizumab as monotherapy or in combination with platinum-based chemotherapy. Immune-related adverse events (irAEs), complications, tumor size changes, overall response rate (ORR), and disease control rate (DCR) were evaluated. Results: Lung tumors, treated with cryotherapy, demonstrated continuous reduction from the baseline (22.4 cm2 vs. 14.4 cm2 vs. 10.2 cm2, p &lt; 0.001). Similar changes were observed in pulmonary tumors in the control group (19.0 cm2 vs. 10.0 cm2, p &lt; 0.001). The median change in pulmonary tumors between two groups was not significant (\u221242.9% vs. \u221227.7%, p = 0.175). No significant differences were observed in the ORR (28.6% vs. 23.1%, p = 0.461) or target lesion decrease (\u221224.0% vs. \u221223.4%, p = 0.296) between the groups. However, the DCR was significantly higher in the cryotherapy group (95.2% vs. 73.1%, p = 0.049). No cases of serious bleeding during cryotherapy or pneumothorax were observed. Six patients (25.0%) in the cryotherapy group and eight (26.7%) in the control group experienced irAEs. Conclusions: Our study demonstrated that combined bronchoscopic cryotherapy and immunotherapy with or without chemotherapy may reduce the rate of progressive disease in metastatic non-small cell lung cancer patients while maintaining a satisfactory safety profile.<\/jats:p>","DOI":"10.3390\/diagnostics15020201","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T03:33:02Z","timestamp":1737084782000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Effects of Bronchoscopic Cryotherapy in Metastatic Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Single-Center Prospective Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Gediminas","family":"Vasiliauskas","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"\u017demait\u0117","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-6808","authenticated-orcid":false,"given":"Erika","family":"Skrodenien\u0117","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Po\u0161kien\u0117","sequence":"additional","affiliation":[{"name":"Department of Pathology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertr\u016bda","family":"Maziliauskien\u0117","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurimas","family":"Ma\u010dionis","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6130-0712","authenticated-orcid":false,"given":"Skaidrius","family":"Miliauskas","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatas","family":"Vajauskas","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"\u017demaitis","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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