Lung cancer mainly develops in middle-aged and elderly patients, and middle-aged and elderly lung cancer patients, especially senior lung cancer patients, are often combined with other systemic chronic diseases and cannot tolerate traditional open-heart surgery. Thus many new treatment methods have emerged, including minimally invasive surgery, CT-guided radiofrequency ablation and stereotactic radiation therapy. From the results of current studies, lobectomy with lymph node dissection is still the standard treatment modality for early-stage lung cancer, but limited resection (including anatomical segmental lung resection or wedge resection) can be performed by TV thoracoscopy in some compromisedpatients. CT-guided radiofrequency ablation (RFA) has shown good efficacy and safety as a local minimally invasive treatment for patients who cannot tolerate minimally invasive surgery. safety. Recently, Schneider (2010) performed bipolar or multipolar radiofrequency ablation of lung tumors during open-heart surgery, followed by lobectomy or wedge resection with lymph node dissection, and the results showed no tumor cell necrosis in conventional HE staining, while tumor cell necrosis at the ablation site was confirmed in immunohistochemical staining. The rate of complete tumor cell necrosis was 37.5%, scattered surviving tumor cells accounted for 50%, and incomplete ablation with more than 20% surviving cells was 12.5%, mostly in the internal vascular structure of the tumor or in the marginal area of the tumor, and only in lung adenocarcinoma. If patients can receive radical lung cancer resection surgery, they should not choose radiofrequency ablation.
I. Principle of radiofrequency ablation
Radiofrequency ablation is to apply radiofrequency current with frequency 460-500KHz to the target tumor, so that the polar molecules in the tumor tissue are in a state of excitation, and high speed oscillation friction occurs, and heat is generated. When the local temperature reaches 80-90℃, it can effectively kill the local tumor cells quickly, while the vascular tissue around the tumor coagulates to form a reaction zone, which cannot continue to supply blood to the tumor, which is helpful to prevent tumor metastasis. Since normal tissues of lung can dissipate heat through blood circulation and exhalation of large blood vessels of lung and play the effect of insulation, so that energy can be fully concentrated in the lesion site, coupled with low blood flow of tumor tissues of lung, which makes heat dissipation difficult, heat accumulation and rapid temperature rise, becoming a huge heat storage reservoir, therefore lung tumor is very suitable for RF ablation treatment. Therefore, radiofrequency ablation can treat tumor without damaging normal lung tissues, which provides a new treatment method for non-small cell lung cancer patients with poor cardiopulmonary function and unable to tolerate surgery.
II. Clinical efficacy of radiofrequency ablation in the treatment of lung cancer
In 2000, Dupuy et al. reported three cases of percutaneous radiofrequency ablation for lung malignant tumors, which unveiled the prelude of radiofrequency ablation applied to human body for the treatment of lung cancer.
At present, there are several guidance pathways for radiofrequency ablation of lung tumors, including open-chest, thoracoscopic and CT-guided. Open-chest radiofrequency ablation is generally used for (i) lesions adjacent to fatal structures such as large blood vessels, lung hilum or heart; (ii) generally in cases where the mass is found to be incompletely resected during open-chest. Thoracoscopy is generally used in patients with lung cancer combined with pleural effusion, and RFA of lung tumor and pleural adhesion fixation are performed at the same time. The presence or absence of pleural metastasis or known pleural metastasis needs to be clarified and confirmed by taking biopsy pathology. It is generally believed that CT is the only localization-accurate guidance method for RF ablation treatment of lung tumors, which has the advantages of timely detection of complications, minimally invasive and direct observation of RFA treatment effects. A recent author (Schoellnast, 2011) used PET-CT-guided radiofrequency ablation of lung cancer, but again was not able to determine intraoperatively the presence or absence of residual tumor cells.
Hiraki (2007) showed that the mean 2-year survival time and overall survival rate after radiofrequency ablation of stage I non-small cell lung cancer were 42 months and 74%, respectively. 57% survival rate after radiofrequency ablation of stage I non-small cell lung cancer was reported by Simon (2007). 46 cases of unstaged primary lung cancer treated with radiofrequency ablation were reported by Pennathur et al. Outcome: 2-year survival rate of 50% (95% CI, 33%-65%). lanuti et al. (2008) reported a 2-year survival rate of 78% after 4.5 years of follow-up in 31 cases of inoperable stage I non-small cell lung cancer treated with radiofrequency ablation in 38 cases. lencioni (2008) published in LancetOncology a report on percutaneous lung Results of RAPTURE, a prospective multicenter clinical study of percutaneous radiofrequency ablation for lung cancer: a prospective multicenter clinical trial of 106 lung cancer patients with a total of 183 tumors, 33 of which were non-small cell lung cancer, at seven clinical trial centers from Europe, the United States, and Australia between July 2001 and December 2005, with a 2-year survival rate of 92%. The authors’ unit has started CT-guided radiofrequency ablation for lung malignancies since 2006 and has completed nearly 300 cases so far, summarizing the results of 100 follow-up cases with a median survival time of 28 months for early-stage lung cancer and an overall 2-year survival rate of 57.7%.
In a study by Dupuy (2006) comparing radiotherapy alone with radiotherapy combined with radiofrequency ablation needle for 24 cases of inoperable stage I non-small cell lung cancer: the cumulative survival rates at 2 and 5 years were 50% and 39%. The investigators concluded that when tumor radiotherapy is given, oxygen is essential in radiologically damaging DNA and killing tumor cells, so radiotherapy is very effective against oxygen-rich cells at the tumor margins, but radiotherapy is less effective against oxygen-depleted cells in the central region of the tumor, which can be killed by heating (radiofrequency ablation), so the two have complementary effects and RFA combined with radiotherapy increases the therapeutic effect.
Zemlyak (2010) retrospectively compared the results of sublobar resection (25 cases) and radiofrequency ablation (22 cases) that were not suitable for lobectomy: there was no statistical difference in overall survival and tumor-specific survival. kim (2011) retrospectively compared the results of surgery (14 cases) and radiofrequency ablation (8 cases): overall survival was higher in the surgery group from the trend, but after statistical treatment differences.
Based on these results, Professors Cackler and Abbas of the Department of Surgery at the University of Pittsburgh Medical Center even wrote a paper entitled “Radiofrequency ablation as an effective alternative to lobectomy” in the first issue of JAAPA in 2009, suggesting that radiofrequency ablation is an effective alternative to lobectomy for early inoperable lung cancer, especially for tumors smaller than 5 cm. It was suggested that radiofrequency ablation is an effective treatment for inoperable lung cancer, especially for tumors smaller than 5 cm.
Evaluation of radiofrequency ablation for lung cancer
1.CT: Generally speaking, if the residual reinforced foci appear in the treated area after 3 months of recent review and the low density is surrounded by irregular reinforced ring, the treatment is considered unsatisfactory; if the tumor necrotic area is significantly reduced and its surrounding is surrounded by clear and sharp reinforced ring in the long term (3-6 months) review, indicating that the tumor is not significantly re-growing, the treatment of RF ablation is considered appropriate. CT images can only show the morphological changes of the lesion, and the lung tumor does not shrink significantly in the early stage after RFA treatment, and even some patients do not have obvious changes in CT image size due to local edema and other factors. Therefore, the efficacy of RFA cannot be judged only by CT images and morphological changes in the early stage of RF ablation.
2. FDG-PET and PET-CT: Morphological changes of tumor after RF ablation treatment are often later than metabolic changes, so FDG-PET is more accurate than enhanced CT scan to determine the efficacy. By comparing the changes of tumor tissue metabolism before and after RFA treatment, the recent therapeutic effect of RFA can be accurately judged, providing more precise therapeutic target areas for further external radiotherapy or another RFA treatment.
It is recommended to evaluate the efficacy using ResponseEvaluationCriteriainSolidTumors (RECIST). CT is the most convenient and practical for efficacy evaluation after 3 months; CT evaluation within 1 month is defective because reactive congestion and fibrous tissue proliferation around necrotic foci generally have not disappeared during this period, and CT is difficult to distinguish from residual or recurrent tumors based on the size and density changes of lesions.
3.Tumor markers: CYFRA21-1, CEA, NSE and other tumor markers are the most valuable molecular tumor markers for diagnosis of lung cancer, and their expression levels have important reference values for diagnosis, monitoring and treatment of lung cancer.
4.Immune function: By detecting T/B lymphocyte subsets and NK cell indicators, the changes of immune function of patients before and after RFA are monitored.
5.Pathology: The pathological results can be obtained by puncture biopsy of the lesions after RFA treatment, and direct evidence for judging the efficacy can be obtained through the pathological changes such as apoptosis and necrosis of tumor tissues.
IV. Factors of imaging radiofrequency ablation for lung cancer treatment
The efficacy of RFA for lung cancer is not related to the histological type, but closely related to the size and location relationship of lesions, etc.
1.Size: for peripheral tumors less than 5 cm in diameter, especially less than 3 cm, one treatment can completely destroy the cancerous tissues and has the best effect. For lesions larger than 5cm in diameter, multi-level treatment (conformal radiofrequency ablation) with multiple needle puncture is needed to make the coagulation and necrosis areas superimposed on each other, so that the whole lesion can be treated more thoroughly.
2.Location: the efficacy of peripheral type (more than 2cm from the lung door) lung cancer is better than that of central type lung cancer, mainly because the central type lung cancer mass is located in the large blood vessels of the lung door, the blood flow is faster and takes away a lot of heat, which also causes the heat in the tumor not to accumulate easily, making it difficult to form coagulative necrosis; secondly, the central type lung cancer mass is larger, so it is difficult to be fully and completely destroyed at one time when radiofrequency is used; again, for tumors with deeper sites, considering For the reason of operation safety, the depth of RF needle piercing is not deep enough to cause incomplete ablation, so it is necessary to cooperate with radiotherapy.
3.RFA treatment range: From the perspective of clinical treatment, the more tumor coagulation necrosis foci, the bigger the better. Therefore, it is better for RF ablation treatment range to exceed 0.5-1cm of tumor edge to kill the most active peripheral part of tumor growth (radical RF ablation), so that a coagulation zone can be formed between normal lung tissue and tumor to ensure tumor-free growth area and prevent tumor recurrence.
4.Comprehensive treatment: The standard treatment for locally advanced non-small cell lung cancer that cannot be surgically removed is synchronized chemoradiotherapy. The combination of RFA and radiotherapy can significantly improve the local control rate because of the presence of radiation-insensitive or radiation-resistant tumor cells, while RFA treatment uses high temperature to destroy local oxygen-depleted tumor cells. beland (2010) recommends that the scope of radiofrequency ablation be as large as possible, and the combination of adjuvant radiotherapy can reduce local recurrence if necessary. Systemic therapy, including chemotherapy and targeted therapy, is required for patients with mediastinal and distant metastases.
V. Complications of lung cancer treated by radiofrequency ablation
Intraoperative complications of radiofrequency ablation for lung cancer mainly include pneumothorax, pleural effusion, fever, chest pain, cough, hemoptysis, etc. Most of them are mild, and only some require special treatment. In a systematic review study, the incidence of operation-related complications ranged from 15.2% to 55.6%, and the mortality rate was 0% to 5.6%. The most common complication was pneumothorax, with an incidence of 4.5% to 61.1%, most of which resolved spontaneously, with only 3.3% to 38.9% (mean 11%) requiring placement of closed chest drains. Pleurisy or a small amount of pleural effusion requires closed chest drainage in less than 10% of patients.
The main common postoperative complications are fever and bloody sputum. Postoperative fever in 70% of patients, mostly low fever, is related to coagulation and necrosis of tumor lesions and absorption by the body. For those with larger tumor lesions, the fever is higher, but generally does not exceed 39℃, and it can be reduced to normal in about 1 week after applying antibiotics. Bloody sputum is related to puncture injury or inflammatory reaction of tissues after treatment, and symptomatic treatment can be given to stop bleeding.
In conclusion, RFA can reduce tumor load, especially for elderly early-stage non-small cell lung cancer patients, and RFA as a local physical targeting therapy can obtain satisfactory local control rate, create favorable conditions for subsequent radiotherapy and targeted therapy, and help improve the efficacy of integrated therapy such as chemoradiotherapy and targeted therapy.