1. Correlation of therapeutic efficacy. It has been reported in the literature that the efficacy of radiofrequency thermal coagulation with cluster electrodes in the treatment of lung cancer is not related to the tissue type of lung cancer, but more closely related to the size and location of the lesion. The treatment range should preferably exceed the tumor margin
0.5~1cm to kill the peripheral part where the tumor growth is most active. ①For 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. ②For lesions larger than 5cm in diameter, multiple needle punctures and multi-level treatments are needed to make the heat-damaged areas superimposed on each other in order to make it possible to treat the whole lesion more thoroughly. The main reason is that the mass is often wrapped around or adhered to the bronchus and large blood vessels, so it is difficult to ensure that these important organs are not damaged and that the treatment is complete at the same time. Since metastatic lung cancer is often multiple and the lesions vary in size, only the more suitable lesions can be selected for treatment, and radiofrequency treatment can only be used as a kind of tumor reduction surgery.
2. Judgment of therapeutic effect. It mainly relies on CT, MRI and other imaging changes, especially CT can accurately guide the insertion of RF needle and show the pathological changes after lung cancer treatment.
CT can determine the changes of lesion size and density before and after RFA treatment for lung cancer, which provides important parameters for the prognosis of RF treatment for lung cancer and provides the basis for repeated treatment. Chen Shilin, Department of Thoracic Surgery, Jiangsu Cancer Hospital
①CT Observation of tumor enlargement during treatment and reduction of CT value is considered effective. If the lesion does not shrink significantly but the enhancement contrast does not show up, it also suggests that the treatment is effective.
②For the tumor near the chest wall, color ultrasound to observe the blood supply of the tumor, and the abnormal blood flow decreases or disappears is considered effective.
(3) PET examination before and after surgery to detect metabolic changes in tumor tissue to distinguish necrotic from surviving tumor tissue.
The metabolism of necrotic tumor tissue is significantly lower than that of surviving tumor tissue, and the morphological changes of tumor after treatment are often later than the metabolic changes. Therefore, PET examination can be used as an indicator of the early efficacy of radiofrequency treatment for lung cancer. However, the high cost of the examination has limited its clinical application.
④ Necrotic lesions show high signal in T1 and low signal in T2 on MRI.
For patients with surgical resection after radiofrequency or postoperative local biopsy to obtain pathological diagnosis, direct evidence for efficacy determination can be obtained. The literature reports that the clinicopathological characteristics of lung cancer after RF ablation are: large areas of coagulative necrosis are seen in lung cancer tissues, some of which show multifocal punctate necrosis with liquefied cavities, scattered cancer cell nuclear consolidation and nuclear fragmentation in the center and edges of necrotic lesions, vacuolar degeneration and eosinophilia in some of the cancer cells remaining at the edges of necrotic foci, and vasodilatation and congestion in adjacent normal lung tissues without obvious inflammatory reactions. Pathologically, it was confirmed that radiofrequency ablation has obvious killing effect on lung cancer cells and can inhibit angiogenesis of tumor tissues. The present results indicate that the recent efficacy of this method is still satisfactory, and some lesions become larger during the postoperative period of 1 month-3 months and become stable thereafter. the size of lesions and cavities is relatively unchanged after 6 months, and the increase of lesions after 6 months represents local recurrence. The change in lesion size is a key indicator to evaluate the efficacy, but it has been pointed out that RFA can lead to inflammation of the tissue in the area around the lesion, and the extent of the lesion increases in the early postoperative period and decreases thereafter, so the use of size as a criterion to evaluate the efficacy early after surgery may be inaccurate. Some authors have noted that the inflammatory and hemorrhagic layers around the ablated area usually return to the initial lesion size by 30 d postoperatively. Another central issue affecting the evaluation is how to determine whether there is residual surviving tumor in the ablated lesion area, Jin suggested that CT images should not have any enhancement in the ablated area when enhanced CT is performed at the end of ablation, Lee et al. suggested that the increase in 10HU CT values before and after enhancement represents surviving unablated tumor. In contrast, Sharma et al. observed by CT follow-up that localized lymph node enlargement in the hilum and mediastinum could be accompanied by enlargement in the first month after RFA, but could gradually decrease in the first 6 months after RFA. In addition, enlarged lymph nodes in a few cases may have increased FDG uptake or have enhancement in enhanced CT. Although CT plays a pivotal role in the postoperative follow-up of RFA, it is not sufficient to evaluate the efficacy of CT alone. belfiore found that CT evaluation is prone to false negatives, and that some biopsy specimens of ablated areas were found to have pathologically confirmed tumor cells, even in cases where the area of the lesion was reduced. the WHO also recommends the following criteria to determine disease recurrence or progression after RFA: ① Ablated foci (ii) Contrast enhancement of the ablated foci: >50% baseline enhancement after 180s; nodular enhancement >15 mm; any central enhancement >15 HU; (iii) Local or distant lymph node enlargement and new intra-pulmonary or extra-thoracic lesions also represent progression.
Radiofrequency ablation treatment: CT scan confirms that the exit of the sub-electrode needle is located at the center of the tumor, opens the sub-electrode needle 1 cm to fix the puncture needle and starts treatment. The radiofrequency pulse power is treated from small to large in sequence, the sub-electrode is gradually released from 1cm and 2cm, and according to the magnitude of temperature rise, it is opened to the corresponding tumor size and hooked back to a spherical shape. With the increase of energy and the extension of treatment time, the tissue temperature gradually rises and reaches the set value, the radiofrequency treatment machine with computer-controlled energy automatically controls the size of output power to keep the treatment temperature to maintain a certain treatment time and complete a treatment. If the tumor is larger, the treatment point will be adjusted for conformal treatment with the principle of near first and then far. The number of treatments and the length of treatment time for each tumor are related to the tumor size, location and blood supply. For tumor diameter less than 3cm do 1 target point, temperature up to 95℃ maintain 10 minutes treatment. Those larger than 3 cm in diameter take multiple targets at 2 cm intervals, with each target treated for 10 minutes of treatment until the targets are stacked to encompass the entire tumor volume. In our case, the maximum diameter of 10 cm tumor reached 8 targets for 80 min. the complete necrosis rate was 69-100% for tumor diameter ≤3 cm, and 23-39% for tumor diameter more than 3 cm. the ablation was more complete for tumor diameter ≤3.5 cm by PET/CT, and tumor diameter ≥3.5 cm often had residual. The tumor necrosis, fibrotic scar formation, inflammatory cell infiltration in surgically resected specimens after ablation of primary lung cancer, 65~87% of tumor cells died, especially when the tumor was ≤2cm, the cancer cells were more likely to reach complete death. One to three months after treatment, fine needle aspiration biopsy was performed on the treated area, and pathological and cytological examinations were performed on necrotic tissue, and no tumor cells were detected in the original tumor site. After 6 months, glassy and fibrotic scars were formed in the treated area. Most of the surrounding normal tissues showed no damage except for a small number of cells showing degenerative changes with inflammatory cell infiltration. Survival benefit: RF ablation combined with radiotherapy can significantly prolong the survival of patients, effectively reduce the local recurrence rate of lung cancer and improve the functional status of patients. As long as the lesions do not invade important organs such as lung hilum and trachea, most of them can achieve complete inactivation of tumor tissues after multiple treatments. The local recurrence rate after radiofrequency treatment is significantly lower than that of other therapies, which is only about 15%. Follow-up of patients after radiofrequency ablation showed that the one-year survival rate of stage I non-small cell lung cancer was 78%, the two-year survival rate was 57%, and the three-year survival rate was 36%, which was better than the one-year survival rate of radiation therapy of 57%, the two-year survival rate of 36%, and the three-year survival rate of 21%. The main cause of death after radiofrequency ablation treatment was distant metastasis, and metastatic recurrence cases tended to have larger tumors and more advanced disease.
Quality of life: Most patients in the RF treatment group showed pain reduction, weight gain, improved KPS scores, and significant improvement in quality of survival after treatment.
The quality of survival was significantly improved at 3 and 6 months after treatment. The rate of complications, nausea, vomiting, weight loss, bone marrow suppression, and decreased immunity, which affected the quality of survival, was greatly reduced with radiofrequency treatment compared with systemic chemotherapy. Physiological condition, social family, emotion, and functional status were significantly improved, confidence in treatment increased, and treatment compliance increased; meanwhile, tumor-related symptoms such as cough, pain, shortness of breath, and fatigue were reduced in patients, and the quality of survival was significantly improved.
Immune function: Radiofrequency ablation has the secondary (or distal) effect of immune activation, which can improve the immune function of the body to a certain extent. After treatment, immunosuppression is reduced, the percentage of CD3+, CD4+ and NK cells and the ratio of CD4+/CD8+ cells are significantly increased, and the killing activity of NK cells is also increased. Radiofrequency ablation can effectively destroy the microvasculature of tumor tissues, inhibit the formation of blood vessels and reduce the blood supply to the tumor.
Studies on radiofrequency ablation followed by surgical resection: radiofrequency ablation of small hepatocellular carcinoma can achieve similar long-term survival outcomes as surgical resection treatment. The advantages of surgical resection over the two are accumulated experience, high prevalence and low recurrence rate, while percutaneous local ablation has low complication rate,
Thirty-eight percent of patients with stage I or II non-small cell lung cancer have complete ablation of their tumors, and 87% have massive tumor inactivation. CT-guided ablation of lung cancer with surgical resection pathology at two weeks showed a 67% complete ablation rate. An average of 8 mm beyond the complete ablation margin still showed ablation without histological changes in the surrounding lung parenchyma, confirming the safety and controllability of radiofrequency ablation.
Efficacy of radiofrequency ablation for lung cancer
The results of a prospective clinical observation of RFA for lung cancer in 106 patients with seven medical centers in the United States, Europe, and Australia published in Lancet Lancet-Oncology in July 2008, chaired by Professor Riccardo Lencioni of the Department of Interventional Oncology, University of Pisa, Italy, showed that 106 patients were not suitable for surgical resection, radiotherapy, and chemotherapy treatment, including 33 cases of NSCLC, 53 with lung metastases from intestinal cancer, and 20 with other primary lung cancers. This 106 patients had 183 lung cancer tumors less than 3.5 cm in diameter (mean 1.7 cm). Patients underwent preoperative CT-guided lung tissue biopsy and were followed up for at least two years after surgery. Among them: 99% of patients could correctly place the RF ablation electrode needle according to the surgical protocol; 75 of the 85 patients observed within one year achieved complete remission, with a complete remission rate (CR) of 88%, with no difference between NSCLC and lung metastases. 1-year and 2-year cancer-related survival rates for NSCLC were 92% and 73%; 1-year and 2-year cancer-related survival rates for lung metastases from intestinal cancer were 91% and 68 The 1-year and 2-year cancer-related survival rates for other metastases were 93% and 67%; the 1-year and 2-year survival rates for NSCLC were 70% and 48%; the 1-year and 2-year survival rates for lung metastases from intestinal cancer were 89% and 66%; the 1-year and 2-year survival rates for other metastases were 92% and 64%; the 2-year overall survival rate for stage I NSCLC (n=13) was 75% and the cancer-related survival rate was 92%; postoperative complications were 27 cases of pneumothorax and 4 cases of pleural effusion requiring drainage. No significant pulmonary impairment was reported; no deaths were reported within 30 days after the 137 RFA procedures in this study.
Combined radiofrequency ablation with radiotherapy and targeted therapy for lung cancer
Central type lung cancer masses are close to large blood vessels and large airways in the hilum, and blood flow or air takes away a lot of heat energy, so it is not easy to accumulate heat in the tumor, and it is difficult to form coagulative necrosis, so the efficacy is poor. It is generally believed that oxygen is indispensable in radiation damaging DNA and killing tumor cells when tumor radiotherapy is given, so radiotherapy is very effective on oxygen-rich cells at the tumor margin, but radiotherapy is less effective on oxygen-depleted cells in the central area of the tumor, which can be killed by heating (radiofrequency ablation), so the two have complementary effects and RFA combined with radiotherapy can increase the therapeutic effect.
Patients with intermediate to advanced lung cancer also need systemic therapy, including chemotherapy and targeted therapy, which can improve the efficacy of treatment. An analysis of the two treatment regimens revealed that for patients with the indicated disease, the treatment efficiency of patients receiving the combination of RFA and Gefitinib was significantly higher than that of patients receiving RFA alone, and their quality of life was also significantly better after the combination treatment group received treatment than the RFA treatment group alone. The combination of RFA and Gefitinib for NSCLC resulted in better treatment outcomes than the RFA alone regimen. This provides a better combination of treatment for patients with advanced NSCLC who cannot tolerate conventional radiotherapy.
For patients who cannot receive or tolerate surgery, radiotherapy or chemotherapy, the preferred treatment is radiofrequency ablation, which has the characteristics of short treatment time, no general anesthesia, short hospitalization period and low cost, overcoming the shortcomings of traditional treatment methods and has become a reliable minimally invasive treatment tool. As a new treatment method for peripheral lung cancer, it has great potential for development. With the aging of the population, the proportion of lung cancer in middle-aged and elderly patients is increasing year by year, these patients often have comorbidities and are not suitable for conventional open-heart surgery, so many new treatment methods come into being, those who are not suitable for surgery should choose radiofrequency ablation, foreign literature reports that the indications for radiofrequency ablation for lung tumors are locked in early stage NSCLC and lung metastases, but in view of the actual situation and ethics in China more lung cancer patients willing to receive radiofrequency ablation treatment belong to the intermediate and advanced stages (inoperable). The reduction of tumor in patients with locally advanced and metastatic lung cancer provides the conditions for comprehensive treatment. Radiofrequency ablation therapy should be combined with chemotherapy, targeted therapy or/and radiotherapy before and after.