Lung cancer is the leading cause of cancer death worldwide, with more than 160,000 deaths worldwide each year.1 In 2010, approximately 569,490 people died of lung cancer in the United States, accounting for 29% of all cancer deaths and the leading cause of cancer death.2 Surgery is the primary treatment for early-stage primary lung cancer, but in more than 15% of patients with stage I or II non-small cell lung cancer (NSCLC) and 30% of patients older than 75 years of age, surgery is not available.3 For the majority of patients with inoperable lung cancer, there is little benefit from conventional radiotherapy. However, more than 15% of patients with stage I or II non-small cell lung cancer (NSCLC) and 30% of patients older than 75 years of age cannot be treated surgically.3 For the majority of patients with inoperable lung cancer, there is little benefit from conventional radiotherapy, so many new local treatments have emerged, including local ablation and stereotactic radiotherapy.4 Since the first report of local thermal ablation for lung cancer in 2000, the number of patients treated each year has increased. Since the first report of local thermal ablation for lung cancer in 2000, the number of patients treated each year has increased rapidly, and it is expected that the number of lung tumor cases treated with thermal ablation will exceed 150,000 cases/year in 2010.5 This article introduces the different techniques, clinical indications, safety and efficacy of local thermal ablation for lung cancer in recent years. Local thermal ablation techniques (a) Radiofrequency ablation (RFA): RFA is the most widely used ablation technique for the treatment of solid tumors, which is based on the principle that radiofrequency electrodes are punctured into the tumor tissue under the guidance of images. The local temperature can reach 60-120 ℃, and when the tissue is heated above 60 ℃, it can cause coagulative necrosis of cells. The volume of RFA ablation depends on the heat conduction generated by radiofrequency ablation and the heat convection between circulating blood and extracellular fluid. (b) Microwave ablation (MWA): MWA generally adopts two frequencies, 915 MHz or 2450 MHz. The microwave electric field, under the action of alternating current, generates extremely high speed vibration of polar molecules in the tumor tissue, generating high temperature of up to 60-150 ℃ in a short time. Since the radiator concentrates the microwave energy in a certain range, it can effectively radiate to the desired target area. MWA can produce a larger heating range compared with the energy of RFA.7 Regardless of the type of RFA electrode (single electrode/multi-electrode/cold cycle), the diameter of thermal radiation is 2-4 cm, and a single microwave antenna can reach 3 or 5 cm. For larger tumors, the simultaneous application of multiple microwave antennas can increase the ablation volume, and there is synergy between multiple antennas, but the placement of multiple electrodes in the RFA will produce current interference between the electrodes and affect the ablation efficiency.8 (c) Cryoablation: With the development and application of argon-helium cryoablation equipment, cryoablation has become the most popular treatment for tumors. With the development and application of argon-helium cryoablation equipment, cryoablation has also become one of the common ablation techniques for solid tumors. The principle is that the high-pressure argon gas can be cooled to -140°C. When the temperature is below -40°C, the target tissue can be damaged by the following mechanisms: denaturation of tissue proteins, cell lysis caused by the change of osmotic pressure inside and outside the cells and the “icing” effect, tissue ischemia caused by microvascular embolism, etc.9 The ice ball observed by CT or MRI can The ablation area can be directly compared to the tumor border, allowing the surgeon to treat tumors in close proximity to important structures, and to determine the boundary of the cryoinjury, which is roughly within 4-6 mm of the innermost edge of the ice sphere. Unlike radiofrequency ablation and microwave ablation, the heat deposition effect in the respiratory tract does not affect the volume of cryoablation, and as with microwave ablation, cryoablation using multiple probes allows for the treatment of larger tumors. (iv) Laser ablation: Laser ablation is a thermal ablation technique that uses Nd:YAG laser with 1064 nm wavelength or a continuous wavelength (820 nm) laser as the energy source and converts light energy into heat energy through the interaction between the laser and the tissue. The energy is transmitted through a sheathed adjustable fiber inserted into the tumor, and the transmission of photons causes tissue heating, resulting in protein denaturation.10 The size of the ablation zone is influenced by the charring of the tissue near the electrode. Cooling of the fiber with an open or closed cooling system allows for increased energy reserve in the tissue. In addition, the use of multiple fibers inserted into the tumor can increase the extent of the ablation zone. Indications and contraindications for local thermal ablation (a) Indications for radical treatment 1. primary peripheral lung cancer11-13: single lesions that are intolerant to surgery or unwilling to undergo surgery or recurred by other local treatments (e.g., conformal radiotherapy), with no metastases from other sites and a maximum tumor diameter of ≤3 cm. 2. metastatic peripheral lung cancer11-13: certain biological features that indicate a better prognosis The metastases in the lung (e.g. sarcoma, kidney cancer, colorectal cancer, breast cancer) with good prognosis. The number of lesions on one side of the lung is ≤ 3, the maximum diameter of the tumor is ≤ 5 cm, and there is no metastasis from other sites. (2) Indications for palliative treatment The purpose of treatment is to minimize the tumor load and alleviate the symptoms caused by the tumor, for patients who cannot reach the conditions of radical treatment, the indications can be appropriately relaxed compared with those of radical treatment. If the maximum diameter of the tumor is >5cm, multiple needles, multiple points or multiple treatments can be performed or combined with other treatments; if the tumor invades the ribs or thoracic vertebrae and causes intractable pain, it is not necessary to ablate the whole tumor, but to inactivate the local tumor bone invasion, which can achieve good pain relief effect14-15. (C) Contraindications for local thermal ablation11-13 1. The lesion is ≤1cm away from the lung door. The therapeutic target skin distance (referring to the distance from the puncture point to the lesion puncture channel) is <2 cm, and there is no effective puncture channel. 2, Infectious and radiological inflammation around the lesion is not well controlled. 3.Patients with severe bleeding tendency, platelets less than 50×109 /L and serious disorders of coagulation system (prothrombin time >18S, prothrombin activity <40%). 4. Malignant pleural effusion ipsilateral to the ablation lesion is not well controlled. 5.Patients with severe hepatic, renal, cardiac, pulmonary and cerebral insufficiency, severe anemia, dehydration and serious disorders of nutritional metabolism that cannot be corrected or improved within a short period of time, severe systemic infection and high fever (>38,5℃). 6. Advanced tumor patients with KPS score 70 and psychiatric patients are not suitable for microwave ablation treatment. (1) Imaging evaluation 1. CT: The immediate change after ablation therapy is the reduction of CT value, surrounded by concentric circles with different degrees of attenuation around the ablated tumor, which is called the “cap badge phenomenon”.16 The lesion increases and shows a frosted glass-like reaction zone around it, which is due to the inflammatory exudation of normal tissue after heating. Anderson et al17 suggested that the presence of a 4 or 5 mm frosted glass-like reaction zone around the lesion could be an early postoperative sign of complete ablation. The pattern of changes in the postoperative intensive CT scans at 1, 3, 6, and 12 months was as follows: the lesion increased in size during 1 to 3 months after ablation, and gradually decreased in size after 3 months, surrounded by a clear and sharp intensification ring. If the treated lesion does not shrink significantly, the CT value does not change after the enhanced CT scan, which also indicates that the treatment is effective, and cavity-like changes can be seen in about 25% of cases after ablation.18 CT is the most convenient and practical method to evaluate the efficacy after 3 months. PET-CT: The morphological changes of tumor after ablation therapy are later than the metabolic changes, so PET-CT is more accurate than CT in determining the efficacy.20 By comparing the metabolic changes of tumor tissues before and after treatment, the recent therapeutic effect can be accurately judged, and more accurate therapeutic targets can be provided for further radiotherapy or ablation therapy. Within 1 month of ablative treatment, because the reactive congestion and fibrous tissue hyperplasia around the necrotic foci have not yet disappeared, it is difficult to distinguish them from residual or recurrent tumors based on the size and density of the lesions alone, and PET-CT is appropriate to evaluate the efficacy at this time.19 Yoo21 studied 26 cases of early-stage NSCLC with 18F-FDG-PET follow-up at the early stage and 6 months after treatment. It was found that early PET scans, especially within 96 hours after ablation, were not predictive of efficacy, while 6-month follow-up PET was predictive of efficacy. PET as a follow-up tool was limited by its poor spatial resolution and significantly higher peripheral FDG activity due to the inflammatory response around the tumor after ablation. (b) Radiofrequency ablation Hiraki22 et al. applied percutaneous RFA to treat 20 cases of stage I NSCLC (median age 75,6 years, mean maximum tumor diameter 2,4 cm, median follow-up time 21,8 months), with local control rates of 72%, 63% and 63% at 1, 2 and 3 years, respectively, and overall survival rates of 90%, 80% and 74% at 1, 2 and 3 years, respectively, with a mean survival period of 42 months. Tumor-specific survival at 1, 2, and 3 years was 100%, 93%, and 83%, respectively. Simon et al. reported the long-term outcome of a group of 153 patients treated with percutaneous RFA.23 Among them, the 1-, 2-, 3-, 4-, and 5-year overall survival rates for NSCLC (n=75) were 78%, 57%, 36%, 27%, and 27%, respectively. The 1-, 2-, 3-, 4-, and 5-year overall survival rates for lung metastases from colon cancer were 87%, 78%, 57%, 57%, and 57%, respectively. Patients with tumors ≤3 cm in diameter had a significant survival advantage (P < 0.002), with a median time to progression of 45 months, while patients with tumors >3 cm in diameter had a median time to progression of 12 months. A prospective multicenter clinical trial of 183 tumor lesions (≤3 or 5 cm in diameter) in 106 patients with lung cancer (33 with NSCLC, 53 with lung metastases from rectal cancer, and 20 with lung metastases from other malignant tumors) at 7 clinical trial centers in Europe, the United States, and Australia between July 2001 and December 2005, all of whom were unsuitable for All patients were not suitable for surgical resection and radiotherapy or chemotherapy. The results showed that the 1-year and 2-year survival rates of NSCLC after RFA were 70% and 48%, respectively, and the 2-year tumor-specific survival rate of stage I NSCLC was as high as 92%. The 1-year and 2-year survival rates of lung metastases from colorectal cancer were 89% and 66%, respectively. The 1-year and 2-year survival rates for lung metastases from other malignancies were 92% and 64%, respectively. Beland25 reported 79 cases of percutaneous RFA for NSCLC with a mean follow-up of 17 months (1 to 72 months) and no recurrence in 57% of patients, and a mean follow-up of 14 months (2 to 48 months) and recurrence in 43% of patients. The median disease-free survival was 23 months. Chua26 et al. reported the results of a prospective clinical trial of open percutaneous RFA for lung metastases from colon cancer, in which complete remission, partial remission, stable and its progression were 46%, 26%, 39% and 16% of 148 patients, respectively; median progression-free survival was 11 months, median overall survival was 51 months; 3-year and 5-year survival rates were 60 Baere et al.27 conducted a multicenter prospective study including 60 patients with lung tumors (mean number of tumors ≤5, diameter <4 cm). 97 of 100 tumor lesions were treated with an overall efficiency of 71% and a disease-free intrapulmonary survival rate of 34% at 18 months of follow-up. The overall survival rate at 18 months was 76% for patients with primary lung cancer and 71% for metastatic lung cancer.28 A prospective study by Dupuy et al28 reported 24 patients with non-surgical stage I NSCLC treated with CT-guided RFA followed by radiotherapy (at a dose of 66 Gy). All tumors received RFA at temperatures above 60°C, with a mean ablation time of 6, 8 minutes. The mean follow-up time was 26, 7 months, and the cumulative survival rates at 12, 24, and 60 months were 83%, 50%, and 39%, respectively. In China, Liu Baodong et al29 treated 100 patients with inoperable lung tumors with RFA, and the overall survival time for the whole group was 13,0 months, with a 1-year survival rate of 51,0% and a 2-year survival rate of 32,5%, with no statistical difference between primary lung cancer and lung metastases (P=0,922). the median survival time for stage I/II lung cancer was 28 months, with a 1-year survival rate of 82,5% and a 2-year survival rate of 57,7%. Currently, most of the literature on pulmonary radiofrequency ablation is based on findings from a single institution. A prospective clinical trial led by the American Society of Surgical Oncology with 25 institutions (looking at 2-year survival and local control rates in patients with stage IA NSCLC who cannot undergo surgery - ACOSOG Z4033) is underway and the final results of this study will be published in 2012. (iii) Microwave ablation Wolf et al30 reported a 1-year local control rate of 67% and 1-, 2-, and 3-year survival rates of 65%, 55%, and 45%, respectively, in 50 patients (27 with NSCLC, 3 with small cell lung cancer (SCLC), and 20 with metastatic lung cancer) treated with CT-guided percutaneous MWA for 82 lung tumors. Carrafiello et al.31 recommended that MWA can replace other ablative means as the preferred modality in some patients. MWA is a thermal ablation technique developed in recent years, and compared with RFA, microwave ablation has the advantages of high target area temperature, large ablation volume, short operation time, and good heat conduction characteristics. As a new treatment, clinical data on the efficacy and safety of MWA for lung tumors are still limited, but the findings of some early clinical trials are encouraging. In China, Liu Aru et al.32 showed a complete remission rate of 17%, partial remission rate of 75%, no change and progression rate of 8%, half-year survival rate of 69%, and 1-year survival rate of 36% in 36 elderly lung cancer patients treated with microwave ablation. In China, Guo Chenyang et al33 treated 47 cases of peripheral non-small cell lung cancer with percutaneous transpulmonary puncture using a monopolar microwave radiation antenna under CT guidance. The effective rate (CR+PR) was 65, 96%. The follow-up ranged from 3 to 40 months, and the 1-, 2-, and 3-year survival rates were 68, 1%, 46, 8%, and, 27, 7%, respectively. (iv) Cryoablation Zemlyak et al34 conducted a randomized prospective study comparing the efficacy of surgical resection, radiofrequency ablation, and cryoablation in 64 patients with stage I NSCLC. Their 3-year survival rates were 87, 1%, 87, 5%, and 77%, respectively, with no statistically significant differences. Wang et al35 reported CT-guided percutaneous percutaneous cryoablation for 187 patients with pulmonary malignancies (89% of the patients had advanced lesions and had failed with conventional treatment). Six-month post-treatment CT scans showed that 86% of the tumors were stable or smaller than before treatment. Overall survival could not be evaluated due to the short follow-up period, but in terms of palliative remission, KPS scores showed significant patient benefit (e.g., improved appetite, weight gain).36 Dawamura et al36 treated 22 metastases in 22 patients and achieved an 80% local control rate and 89% 1-year survival rate. The largest group in China reported that Feng Huasong et al37 used CT guidance to perform percutaneous percutaneous argon helium knife targeted cryoablation in 725 patients with lung tumors and their 816 lesions. The survival rates were 91%, 76%, 36%, and 18% at 0, 5, 1, 2, and 3 years postoperatively, respectively, with a median survival time of 17 and 8 months. The survival rates at 24 months were 86% for stage I-II, 21% for stage III and 10% for stage IV according to the clinical stage of TNM. The results of these clinical trials show that cryoablation for primary and metastatic intrapulmonary malignancies is characterized by high safety and good local control rate, although no follow-up results on long-term efficacy are available. (v) Laser ablation Rosenberg et al38 evaluated the long-term efficacy and safety of laser ablation for the treatment of pulmonary metastases. They treated 108 lesions in 64 patients with a median survival of 23, 1 month and overall survival rates of 69%, 48%, 30%, 30% and 18% at 1, 2, 3, 4 and 5 years, respectively. In patients who achieved definitive local control (31/64), the mean survival was 32,4 months, and the 1,2,3,4,5-year survival rates were 81%, 59%, 44%, 44%, and 27%, respectively. The incidence of pneumothorax was 38%, of which 5% required chest tube placement. 3 patients had grade 3 or higher side effects, including 1 case of bleeding, 1 case of dyspnea, and 1 case of delayed pneumonia and pustule. (vi) Combination of ablation and other treatments The combination of RFA with other treatments is one of the many ablation studies currently underway, including the combination of ablation with surgery, chemotherapy and radiotherapy. The combination of RFA and radiotherapy has been shown to improve local control rate and survival rate with no significant increase in side effects compared with radiotherapy alone. Since the central part of the tumor is more obviously hypoxic and less sensitive to radiotherapy, while RFA is more effective in the central part of the tumor due to easier heat conduction, the coagulative necrotic effect due to heating gradually decreases with increasing distance of thermal radiation, resulting in incomplete ablation of the marginal part of the tumor. Radiotherapy can precisely compensate for the residual tumor marginal part of RFA, which is especially suitable for the inflammatory response of neovascularization after ablation. The peripheral oxygen-rich environment could theoretically enhance the efficacy of radiotherapy, and the resulting formation of superoxide anions and free radicals could cause DNA damage and eventually induce apoptosis. Dupuy et al28 published a study of 24 stage I NSCLC tumors (mean diameter 3, 4 cm) treated with RFA followed by radiotherapy (mean dose 66 Gy), which showed 2- and 5-year survival rates of 50% and 39%, respectively. This result was an improvement over the 5-year survival rate of 27% with RFA alone.39 Grieco et al.40 published a study of 41 patients treated with RFA and MWA for inoperable stage I/II NSCLC in combination with external radiation radiotherapy or iridium brachytherapy. The local recurrence rate was 11,8% (mean follow-up 45,6 months) for tumors less than 3 cm in diameter and 33,3% (mean follow-up 34 months) for tumors larger than 3 cm in diameter, with no survival difference between the external irradiation radiotherapy and brachytherapy groups compared. The toxicity of the combined ablation and radiotherapy group was not significant. In China, Nie Zhoushan et al41 treated 31 patients with stage IIIb or IV NSCLC with post-argon helium knife combined with molecularly targeted drugs (gefitinib or erlotinib), while 101 patients with NSCLC treated with argon helium knife alone were treated as a control group. The survival rates at 0, 5, 1, 2, and 3 years were 100%, 87%, 42%, and 23%, respectively, after post-arthroscopic treatment with targeted agents. In the control group, the survival rates were 90%, 71%, 18%, and 8%, respectively. The difference between the two groups was statistically significant (P<0,05). In China, Du Xianfeng et al42 conducted a meta-analysis of 5 studies of argon helium knife combined with radiotherapy for lung cancer. 2 studies showed that argon helium knife treatment alone resulted in tumor shrinkage, but the overall results suggested that combining radiotherapy with argon helium knife treatment did not result in further tumor shrinkage. 1 study suggested that argon helium knife combined with postoperative chemotherapy improved the 1-year survival rate, but the analysis of survival curves suggested that There was no significant difference in the effect of argon helium knife treatment alone versus argon helium knife combined with radiotherapy on patient survival time. A total of 2 studies comparing patients' postoperative KPS scores suggested that argon helium knife treatment alone was superior to argon helium knife combined with radiotherapy. In patients with advanced NSCLC, argon helium knife treatment alone improved the quality of life, with a similar rate of tumor recurrence in situ as conventional radiotherapy, and no significant difference in median survival time compared with conventional radiotherapy, whereas argon helium knife combined with radiotherapy did not show a better clinical benefit and even decreased the quality of life of patients. If the pain is severe, the amount of opioid analgesics can be increased (e.g., subcutaneous morphine), and sedatives can be given in appropriate amounts (e.g., slow intravenous injection of imipramine). The post-operative pain is usually mild and rarely appears above moderate pain, which can be relieved by non-steroidal drugs. (ii) Post-ablation syndrome: It may occur in about 2/3 of patients and is mainly caused by the absorption of necrotic material and the release of inflammatory factors. The main symptoms are fever (below 38,5°C), malaise, general malaise, nausea, vomiting, etc., which usually lasts for 3-5 days, and a few may last for 2-3 weeks. This condition can be treated symptomatically, and if necessary, glucocorticoids (such as dexamethasone) can be applied in appropriate amounts for a short period of time, in addition to giving non-steroidal drugs. (iii) Pneumothorax: The most common complication after ablation is pneumothorax, with an incidence of 10%-60%, of which no more than 10% require closed chest drainage. Hiraki et al43 retrospectively analyzed 392 tumor lesions in 141 patients and treated 224 lesions with radiofrequency ablation. Of these, the incidence of pneumothorax was 52% and 11% required placement of chest drains. They analyzed the factors associated with the occurrence of pneumothorax and found that males, no history of lung surgery, lesions located in the lower or middle lobe, distance between the tumor and the chest wall, and number of tumors were associated with the occurrence of pneumothorax.The study by Noru-Eldin et al44 yielded the same results, with pneumothorax more commonly associated with emphysema, age greater than 60 years, tumors less than 1, 5 cm, tumors located in the lower lobe of the lung, and an ablation path The lung tissue penetrated was greater than 2, 6 cm or through a large interlobular fissure.45 Gillams et al.45 applied a multifactorial analysis to confirm that the length of the puncture needle or electrode through the lung tissue was an independent risk factor for postoperative pneumothorax. Most pneumothoraces are easily treated or are self-limiting and heal on their own without intervention. If the patient still has gas leakage after chest drainage, pleural fixation, tracheoscopic injection of sclerosing agents, and endotracheal valve placement may be performed.46 (iv) Pleural effusion: A small amount of pleural effusion can often be seen after ablation, the latter being thought to be a sympathetic response of the body to thermal injury. The incidence of pleural effusion requiring puncture/tube placement for drainage ranges from 1% to 7%, and Nour-Eldin et al47 reported that the risk factors for the occurrence of pleural effusion include the use of internal cooling electrode bundles, large lesions, proximity of the lesion to the pleura (<10 mm), and long ablation operation time. (v) Bleeding: The incidence of bleeding in ablation is 7-8% 48, but the incidence of hemoptysis is extremely low. Since ablation itself can make the blood coagulate, even if a small amount of bleeding occurs during the puncture, the bleeding will gradually stop as the treatment progresses, so the incidence of bleeding during the specific treatment is not high. (vi) Tumor implantation: Guihaire et al49 reported that if improperly performed in RFA, it may trigger needle tract implantation metastasis. The occurrence of implantation metastasis can be avoided if the initial puncture is done properly and the electrode is avoided to pass directly through the tumor. Adequate ablation of the peripheral safety belt and cautery of the needle tract during needle exit may reduce the risk of needle tract implantation. (vii) Thermal burns in non-target areas: These include thermal burns in non-ablation areas, such as the leg electrode pad site and its interference with pacemaker leads and pacemaker resuscitators. More dangerous are thermal burns to the tissues (<1 cm) surrounding the ablation target area, including the trachea or large blood vessels. Thorough planning before ablation, including the puncture route and final electrode placement, can avoid damage to these tissues. (viii) Infection Pre-existing lung infections should be treated before ablation. The incidence of lung infection caused by ablation surgery is less than 1%. Antibiotics can be applied routinely for 3 days after ablation surgery, and the time of using antibiotics should be extended appropriately for patients with recurrent attacks of chronic bronchitis. If the body temperature is still >38,5℃ 5 days after ablation surgery, lung infection should be considered first, and antibiotics should be adjusted according to the results of sputum, blood or pus culture. If a pulmonary or thoracic abscess occurs a tube can be placed for drainage and irrigation. In addition, patients are prone to interstitial pneumonia after radiotherapy, and those who undergo ablation on this basis are more likely to have secondary infection, which should be given full attention. (ix) Other rare complications: bronchopleural fistula, exacerbation of chronic obstructive pulmonary disease, acute lung injury, air embolism, etc. have been reported50 , most of which are mild and only some require special treatment. There is no conclusive evidence that RFA can interfere with pacemakers and other devices. In summary, for patients with early-stage NSCLC who are unable to undergo lobectomy, a variety of treatment options exist. The 5-year survival rate for lobectomy can reach 89% if the tumor is less than 2 cm. The 3-D conformal external irradiation radiotherapy technique used in the past achieved a 2-year survival rate of 51%. The newly developed stereotactic body radiotherapy technique has a 3-year survival rate of up to 60%. From the perspective of clinical trials, less research has been reported on thermal ablation techniques, but preliminary results from current studies suggest that thermal ablation techniques have achieved 2-year survival rates of 48-80% for the treatment of lung tumors. Previous oncologists have traditionally classified thermal ablation as a last resort, but in fact thermal ablation for lung tumors, both primary and metastatic lung cancer, can be divided into three main purposes: radical, neoadjuvant, and palliative reduction. The effectiveness and safety of this tool have been clinically proven at present, and further work is needed to change oncologists’ perception of thermal ablation so that this treatment can be applied correctly and in a timely manner. As for the advantages and disadvantages of the various thermal modalities of thermal ablation and their ability to replace surgery in certain patient groups, the efficacy of thermal ablation in combination with other therapeutic modalities remains to be confirmed in larger multicenter clinical trials. Regarding the treatment of lung tumors, minimally invasive treatment is one of the future development directions, which is characterized by small trauma, fast recovery, safety, effectiveness, and convenient operation and wide range of adaptable population. It is believed that this technology will be increasingly used in the comprehensive treatment of lung tumors in the future.