Lung cancer has become the leading cause of malignant tumor morbidity and mortality. Only about 20% of non-small cell lung cancers can be treated with radical surgery, and most lung cancers are already in advanced stages when they are diagnosed. Ablative therapy is a minimally invasive treatment technique that destroys local tumor cells by physical or chemical means under the guidance of imaging, and it is a focal targeting therapy compared to molecular targeting therapy. Ablation of liver cancer has been recognized as a curative method, and the advantages of ablation therapy for lung cancer are gradually gaining attention.
I. Ablation therapy in lung cancer clinical guidelines and specifications
1.Ablation therapy in NCCN guidelines for non-small cell lung cancer in the United States The NCCN guidelines for non-small cell lung cancer in the United States have been formulated since 1995, and surgery, radiotherapy and chemotherapy are recommended as the main treatment methods for lung cancer until 2005. Radiofrequency ablation for the treatment of lung cancer was first reported in 2000, and in 2006 the Guidelines first included radiofrequency ablation (RFA) as a treatment option for patients with lymph node-negative lung cancer who refused surgery, had poor physical strength, and/or could not tolerate surgery due to comorbidities. 2009 Guidelines first included RFA as a stand-alone treatment option for stage I lung cancer with isolated peripheral lesions <3 cm. It can also be used for previously irradiated tissue and as a palliative treatment option. 2010 Guidelines first included tumor ablation in the category of surgical treatment, including RFA, cryoablation, and stereotactic radiotherapy began to be called radioablation. 2013 to present, the Guidelines emphasize that surgical resection is the preferred local treatment for lung cancer patients, and other local treatment modalities include RFA, cryotherapy, stereotactic RFA can be used as lymph node negative patients who refuse surgery due to poor physical status, high cardiovascular risk, poor lung function and/or cannot tolerate surgery due to comorbidities, and is most suitable for treating stage I lung cancer with isolated peripheral lesions <3 cm, as well as for previously irradiated tissues and inclusion in palliative care programs, and also for heterochronic isolated lung metastases in metastatic lung cancer that can receive local treatment.
2. Radiofrequency ablation treatment in the Chinese “Primary Lung Cancer Treatment Specification” The 2011 and 2015 editions of the Specification both propose that lung cancer treatment in China follows the principle of staged multidisciplinary comprehensive treatment. Comprehensive analysis of the patient’s organism condition, pathological type, clinical stage and disease progression trend, rational application of surgery, radiotherapy, chemotherapy and biological targeted therapy, and the combination of standardized treatment and individualized treatment, in order to achieve clinical cure or maximum tumor control, improve the patient’s survival quality and prolong survival. In surgical treatment, for stage I and stage II non-small cell lung cancer that cannot undergo surgery after assessment of cardiopulmonary function, radical radiation therapy, radiofrequency ablation therapy and drug therapy can be chosen.
Indications and contraindications of lung cancer ablation therapy
The Expert Consensus on Thermal Ablation for Primary and Metastatic Lung Tumors (2014 version) classifies ablative treatment for lung cancer into two categories: complete and palliative. Complete ablation refers to ablative treatment that results in complete necrosis of local tumor lesion tissue and has the potential to achieve a curative effect. The purpose of palliative ablation therapy is to minimize the tumor load, relieve the symptoms caused by tumor and improve the quality of life of patients.
The indications for complete ablation are pathologically confirmed early peripheral lung cancer with maximum tumor diameter ≤ 3 cm (author’s note: individual can be ≤ 5 cm), including adenocarcinoma, squamous carcinoma, small cell carcinoma or metastatic lung cancer, where patients cannot tolerate surgery or refuse to undergo surgical resection or other local treatment such as single lesion after recurrence of moderate radiotherapy due to poor cardiopulmonary function or advanced age.
2. Indications for palliative ablation For those who cannot achieve complete ablation, such as tumor maximum diameter >5 cm, or multiple lesions, multiple stitches, multiple points or multiple treatments can be performed, or combined with other treatments. For example, local ablation treatment for refractory pain caused by bone metastasis can achieve pain relief effect.
3. Contraindications of lung cancer ablation therapy: tumor located in the hilar part of lung, invading bronchus above the lobe of lung or tumor is infiltrating; serious functional failure of main organs; active infection; uncorrectable coagulation dysfunction, blood test shows serious hematological disease; poor lung function, large amount of pleural fluid, impaired consciousness or advanced cachexia, expected survival <3 months.
III. Technical operation specification of radiofrequency ablation treatment for lung cancer
1.Principle Radiofrequency ablation (RFA) is the most widely used tumor ablation technique. Under the guidance of image, RF electrode is inserted into the tumor interior, end-cooled single electrode or bipolar single needle or recommended multi-sub-needle electrode can be released conformally according to the shape of the tumor and distributed in the tumor tissue, RF current forms a circuit in the patient’s body, the polar molecules concentrated in the tissue around the electrode vibrate at high speed, molecular friction generates heat energy, heating the tumor tissue to 60~100℃ (average 95℃), causing It can heat up the tumor tissue to 60~100℃ (95℃ on average) and make the cancer cell protein denaturation, lipid layer dissolution, cell membrane destruction and coagulation necrosis. At the same time, it can stop the blood supply to the tumor from the vascular tissues around the tumor and prevent the tumor from metastasis. The antigenicity of the inactivated tumor protein can stimulate the body to produce specific immune effect and exert systemic anti-tumor effect.
2.Treatment process Before treatment, treatment plan should be made according to patient’s imaging data, simulating puncture route, target area needle placement, predicting efficacy and risk; during treatment, percutaneous puncture, calibration, hitting and needle placement should be guided by CT imaging; during treatment, vital signs need to be detected, image monitoring ablation range and possible endangered organ situation and complications; after treatment, evaluation and follow up. If complete ablation is achieved, the treatment can be ended; if there is still residual, additional ablation treatment will be given; if it is ineffective or there is metastasis, other comprehensive treatment methods will be combined.
3.Image-guided puncture
Radiofrequency ablation is performed aseptically under local anesthesia, mainly under CT guidance. Firstly, a metal raster localization ruler is placed at the needle entry position on the body surface, and 9 layers are scanned with 10mm tomography to find the largest level of the tumor and clarify the relationship between the tumor and surrounding larger vessels, bronchi, mediastinum and nerves. In the second step, the largest lesion tomography was used as the center, and then 9 layers were scanned with 5-mm tomography to select the puncture point, puncture access, needle direction, depth and tumor target point in the largest lesion tomography, and to determine the angle between the needle point and the line connecting the target point (Figure ①). In the third step, the puncture needle was placed on the CT laser localization line out of the largest tomography of the lesion using a guide to calibrate the direction of the puncture needle (Figure ②). In the fourth step, the scan is repeated to determine the tail shadow (or extension line) of the puncture needle through the target point (Figure ③). In the fifth step, puncture to the corresponding depth, that is, the center of the tumor can be hit (Figure ④).
4.Treatment target area
In order to obtain the “safe edge” and completely destroy the tumor, the ablation area should reach the surrounding tissues next to the cancer. For infiltrating type or metastatic cancer with unclear boundary and irregular shape, the treatment target area for complete ablation is PTV=5mm outside the clinical target area CTV=10mm outside the naked eye target area GTV. 10mm.
5.Radiofrequency ablation treatment prescription
For regular tumor ≤3cm, single-target RF ablation is used, and the treatment time is 20 min; for tumor diameter 3~5cm, 2-target RF ablation is used, and the treatment time is 30 min; for tumor diameter >5cm, 3-target RF ablation is used, and the treatment time is 40 min. Conformal ablation electrodes can also be used, which is helpful to improve the energy of target area and reduce the damage of normal tissues. The prescription amount of the treatment plan is based on the sub-electrode completely covering the target area, the temperature measured in the center of the treatment reaching 95℃ and the edge exceeding 60℃, and maintained for more than 10 minutes. When the tumor is large or irregular in shape, the prescription amount should cover at least 95% of the target area. Multi-target target area requires concentric circles to lay needles and avoid cold spot areas within the target area when filling. Try to avoid the sub-electrode and ablation area into the restricted organ area.
Usually puncture to the front of the tumor first, the puncture needle starts to puncture to the inside of the tumor under certain energy (60℃), which can prevent bleeding and needle to metastasis; the principle of adjusting the treatment target is near first and then far, the principle of releasing the sub-needle is gradually released to cover the whole tumor target area, when the sub- electrode is opened the pulse power gradually increases the treatment temperature to 95℃, and gradually releases the sub-needle in 1cm unit. The ablation temperature is monitored by sub-electrode temperature measurement point, and the treatment process is monitored by CT.
Clinical application of lung cancer ablation therapy
1.Immediate curative effect
The ablated lesion shows hypointense change, the CT value is reduced, and the foveal or cavity-like shadow may appear. The ablated tumor is surrounded by concentric circles with different degrees of attenuation, which is called the “cap badge” sign. (Figure C and D).
2.Recent curative effect
After 1 month of lung cancer ablation treatment, intensive CT scan shows that the treated area will be slightly enlarged but without vascular enhancement; a ring of enhancement may appear around the periphery, which is called the “eggshell” sign. PET/CT examination may reveal metabolic disappearance, and puncture biopsy may reveal tissue necrosis and inflammatory cell infiltration.
3.Long-term efficacy
After 6~12 months of radiofrequency ablation treatment, the tumor may gradually shrink until it disappears, or form scar or cavity or hard nodule by CT. There is no significant difference in the overall survival rate of percutaneous ablation of early-stage lung cancer compared with lobectomy, and the survival rates of 1 year, 3 years and 5 years reach 97.7%, 72.9% and 55.7%, respectively. Local recurrence was slightly higher with single treatment of radiofrequency ablation, and multiple additional treatments resulted in a lower recurrence rate and higher long-term efficacy. While ablation inactivates tumors and subclinical lesions, it also destroys the confinement factors and macrophage movement inhibitory factors secreted by tumor cells, which fully exposes and releases antigens in the cytoplasm and nucleus. Thus, it can increase the antigenicity, stimulate the specific lymphocyte immune effect and NK cell killing activity, activate the patient’s immune response, and exert systemic effects.
4.Complications
The most common complication of radiofrequency ablation is pneumothorax, which is mostly caused by puncture, with an incidence of about 30%. A small amount of pneumothorax can be left untreated; a medium to large amount of pneumothorax can be treated with chest puncture and suction or placement of closed chest drainage device, and no more than 20% of patients need to place drainage tubes. If the CT-specific guide is used to guide the puncture and treat the tumor in one step, complications are low and pneumothorax rarely occurs. Other complications associated with ablative therapy include pain, fever absorption, pleural effusion, pleurisy, and, rarely, pneumonia, lung abscess, hematochezia, pulmonary hemorrhage, acute respiratory distress syndrome, and, rarely, serious complications such as infection, hemorrhage, and death. Hematochezia is associated with puncture injury or tissue inflammatory reaction after treatment, and hemostatic treatment may be given.
V. Conclusion
Image-guided radiofrequency ablation therapy for lung cancer is minimally invasive and efficient, simple and safe, precisely controlled, completely destructive, repeatedly used, less expensive, and can even be performed on an outpatient basis. The NCCN guidelines in the United States and the lung cancer treatment protocols in China have clearly stipulated that radiofrequency ablation has become a new treatment alternative to surgery for early-stage peripheral lung cancer that cannot be treated surgically.