Cryotherapy is the therapeutic local destruction of living tissue using intense cold (Fig 5). Bronchoscopic cryotherapy probes, which are typically cooled to –40°C, are sequentially applied to endobronchial lesions, inducing several cycles of cooling and thawing and resulting in tumor necrosis. Some investigators have described using catheters that are cooled to about –165°C with tumor freezing times of 3 to 5 min followed by thawing. Unlike heat modalities that impart a risk of endobronchial fire, cryotherapy can be safely performed in high-oxygen settings. Wang et al published a large study on treating thoracic malignancy with percutaneous cryotherapy (PCT) using a 3-mm cryoprobe. The investigators enrolled 187 patients with 234 masses, 196 of which were primary lung cancers. Of the 143 patients with advanced-stage lung cancers, most (89%) had previously undergone treatment with surgery or chemoradiation, or both. One hundred sixty-six lung masses were peripheral, with a mean size of 4.3 cm, and 68 masses were centrally located, with a mean size of 6.4 cm. Most tumors (76%) received a single session of PCT and the therapeutic response was satisfactory, with 86% of tumors demonstrating reduced or stable size. In this study, complications included a 12% pneumothorax rate, brachial and recurrent laryngeal nerve damage in two patients, and procedure-related death in two other patients. In a retrospective study of 22 patients with 34 tumors treated with PCT for nonoperable stage I NSCLC, 2- and 3-year disease-free survival of 78% and 67%, respectively, was reported. The complication rate was significant, however, as 28% of patients experienced pneumothorax, 31% experienced pleural effusions, and 24% had hemoptysis. There were no procedure-related deaths. Moreover, cryotherapy in combination with brachytherapy and percutaneous implantation of controlled-release drugs has been reported to be safe and effective for the treatment of lung cancer.,, A previous study of 625 patients with nonoperative NSCLC showed 1-, 2-, and 3-year survival rates of 64%, 45%, and 32%, respectively. The investigators in this study noted the possibility that cryotherapy can also stimulate the immune system to trigger antitumor effects in human lung cancer.