Application Of Microwave Ablation In Lung Ground Glass Nodules And Small Cell Lung Cancer

Research Background and Purpose:Small-cell Lung Cancer(SCLC)accounts for 10%-15%of all lung cancer types,and the 5-year survival rate is less than 7%.Etoposide or irinotecan combined with platinum-based chemotherapy is the standard treatment for any stage.Patients with limited stage need thoracic radiotherapy when necessary.Prophylactic brain irradiation is recommended to prevent the progression of intracerebral small-cell lung cancer in patients who have achieved complete response after first-line therapy.Although the first-line treatment of small-cell lung cancer is highly sensitive,most patients relapse within 6 months and the second-line treatment is not effective.Microwave Ablation(MWA)is a kind of minimally invasive treatment and causes high temperature in a short period of time under the action of microwave electromagnetic field,resulting in coagulated cell necrosis.The maximum temperature in tumor center is 100℃ to 120℃,and the maximum temperature in the periphery is 60℃ to achieve the purpose of killing tumor cells.MWA can also coagulate blood vessels around the tumor,form a reaction band between normal and cancer tissues to wrap the tumor and prevent tumor metastasis,reduce tumor load and enhance cellular immune function.CT-guided MWA has been carried out in many centers around the world and has proven to be cost-effective and a good patient experience.The first indication is for patients with early clinical primary lung cancer who have no indication for surgery,for whom radical surgery is the best option.However,for patients with serious underlying conditions,poor physical status,limited cardiopulmonary function,and unwilling to operate,local treatment and local control of tumor proliferation need to be solved through other means,and treatment can be achieved through MWA.Local recurrence is the main risk for MWA,and if a patient has a local recurrence after ablation,up to 3 times of ablation can be repeated.Second indication is multiple primary lung cancer treatment,for such patients,due to poor preoperative pulmonary function or expected loss of lung parenchyma,surgical resection is not possible,MWA can save more normal tissues than surgery,so as to maintain the quality of life of patients with postoperative and lung function.Lung metastasis is another indication of MWA,compared with other organs,the lung cancer metastasis is the most common target organs,in certain types of cancer,such as liver cancer and colorectal adenocarcinoma,if all the metastases were removed or inactivated,MWA will improve the prognosis of patients,as a viable option.Local treatment should also be considered when asymptomatic progression is observed in patients undergoing chemotherapy,radiotherapy,or immunotherapy.For localized lesions that do not respond well to systemic therapy,MWA can be used as the ultimate local therapy to achieve complete eradication of the tumor.Possible risks of microwave ablation include:pain and damage to the chest wall,which is more common in subpleural tumors;heat diffusion to surrounding tissues during MWA,which is mild to moderate and lasts for days to weeks;pain associated with MWA treatment usually responds well to analgesics;MWA to parastinal tumor can damage phrenic nerve and affect lung function.MWA to apical tumor can cause cervical plexus injury and sensory or motor dysfunction.Pneumothorax after MWA,the main reason seems to be associated with the insertion of the antenna,in most cases pneumothorax quantity is little,not require additional treatment,the needs of drainage tube placement of pneumothorax because of the increase of pneumothorax,late-onset or recurrent pneumothorax need also the possibility of additional treatment,suggest CT examination is needed within 24 hours after MWA;The blood vessel between ribs damage can lead to bleeding,pulmonary hemorrhage is starting from the rapidly expanding grand-ground opacity on CT,bleeding is usually self-limited,and don’t need to take any action,if bleeding continues,accompanied by uncontrollable coughing,hemoptysis,it may require endotracheal intubation in order to prevent suffocation,destruction of intercostal vessels may result in rapidly progressive hemothorax,which usually requires endovascular or surgical treatment;Small asymptomatic pleural effusion is common after MWA and usually does not require treatment.If the MWA lesion is subpleural,it is caused by the inflammatory response of the pleura.A large number of symptomatic pleural effusion can be treated by pleural puncture and catheter drainage.Post-operative pneumonia is relatively common,and prophylactic antibiotics are necessary before and after MWA,especially in patients with cavity formation at the MWA site,and in patients with emphysema.who are reported to be at increased risk for abscesses.The effectiveness and safety of MWA for non-small cell lung cancer and lung metastasis have been clinically verified in the past.MWA is characterized by small trauma,non-carbonization,strong hemostasis,quick recovery,safety and effectiveness,convenient operation and wide application.In this study,35 patients with LS-SCLC who received MWA combined with radiotherapy and chemotherapy were analyzed for survival,followed by analysis of major complications,to reveal their clinical benefits and safety,and to provide empirical reference for further treatment of this kind.Methods:Clinical data of 35 patients with LS-SCLC who underwent MWA surgery from April 2011 to July 2019 were collected.All the enrolled patients had co mplete staging data of SCLC,and no patients received surgery and MWA for primary lung cancer.Patients who have undergone at least 2 cycles of first-line etoposide+carboplatin/cisplatin chemotherapy with or without thoracic radiother apy,or whose efficacy was evaluated after ablation without new metastasis of symptoms,can continue to complete chemotherapy about 7 days after MWA.The whole process of MWA was conducted under the guidance of CT.Modifield response evaluation Criteria in solid Tumors(mRECIST)were used to evaluate the efficacy of MWA in lung cancer.One month after ablation,the chest enhanced CT was reviewed to evaluate the ablation effect.Afterwards,the efficacy of radiotherapy and chemotherapy and the ablation effect were comprehensively evaluated according to the time of radiotherapy and chemotherapy review(usually every 2-3 months).Complications refer to standards set by the American Society of Interventional Radiology(SIR)for the analysis of severe complications,that is,major complications.Results:Survival analysis:In this study,35 patients with LS-SCLC underwent 38 times of primary lung cancer ablation combined with radiotherapy and chemotherapy,and the median survival time was 48 months,with an average survival time of 50.9±5.8 months(39.6～62.2 months).The 1-year survival rate was 91.67%,the 2-year survival rate was 72.22%,the 3-year survival rate was 66.67%,and the 4-year and 5-year survival rates were 61.11%.Major side effects:perioperative complications occurred during and within one month after the ablation.Common minor complications include cough,blood in sputum,etc.,which are not included in the analysis of this study.This study mainly analyzes major complications requiring hospitalization,including pneumothorax,empyema,herpes zoster and pulmonary fungal infection requiring chest tube.Pneumothorax requiring thoracic catheter occurred in 8 MWA procedures,accounting for 21.1%of the 38 procedures,75%within 24 hours after ablation(n=6),and 25%more than 24 hours after ablation(n=2).Conclusion:Microwave ablation procedure for patients with limited-stage small cell lung cancer is feasible and has controlled complications.With the wide application of multi-slice spiral CT and low-dose CT in lung cancer screening,more and more ground-glass nodule(GGN)is being detected,and has become a health problem because of its malignant potential.Patients diagnosed with lung GGN are generally recommended for short-term follow-up,and once the nodules are identified as invasive lung cancer,surgery is needed.After shared decision making(SDM),both parties agree that:"Direct ablative without pathology or simultaneous ablation with biopsy",which has been included in the latest expert consensus.It is advisable to separate the biopsy before ablation and microwave ablation into two operations to avoid the cover of the ablation target area by bleeding after biopsy.However,there are also false negative biopsies before ablation,so that some patients with malignant potential or malignancy may be missed.Previous studies have shown that tumor cell necrosis occurs gradually after thermal ablation,and tumor cell morphology can be maintained for at least one month after ablation and still be recognized by pathologists.Therefore,post-ablation biopsy is quietly emerging in lung cancer patients,and has been verified by more and more clinical studies,especially in lung cancer patients with solid components.However,clinical studies of post-ablative biopsy in GGN patients are few.In this study,we choose to use core-needle biopsy and microwave ablation antenna to complete the simultaneous operation of ablation and biopsy.The coaxial needle technology of biopsy needle is used to avoid repeated puncture.percutaneous core-needle biopsy(CNB)after melting point selection is a low power of 20 w beyond the original GGN lesions ablation to melt radius of 0.5 cm or tumor cells after microwave thermal coagulation(MTC).The pathological types before and after biopsy were analyzed,and the malignant potential and the proportion of malignant cases(i.e.,the positive rate)were summarized and analyzed,thus concluding that biopsy after ablation was valuable.Methods:Patients with GGNs treated from December 2016 to April 2019 were collected.In addition,under the guidance of a multidisciplinary consultation team(MDT)of experts from radiology,pathology,thoracic surgery,respiratory medicine and oncology,the diagnosis of GGN lesion was made that surgery or follow-up visit was unsuitable,and CNB+MWA surgery was feasible.All patients were operated under awake sedation and local anesthesia,continuous low-flow oxygen inhalation,connected with electrocardiogram monitoring,including blood pressure,heart rate,pulse oxygen,respiratory rate and other indicators.Skin CNB and MWA puncture sites were located by CT.The 16G needle and MWA antenna were respectively punctured into GGN through PTNB and MWA puncture points under the guidance of CT,and the needle core of 16G needle was pulled out.The 18G biopsy needle was punctured into the lesion through 16G trocar,and the pathology was biopsied for staining and immunohistochemistry.The 18G biopsy needle was pulled out and the 16G needle core was reduced.This is a puncture procedure(CNB).The microwave therapeutic instrument was connected to the MWA antenna,the power was adjusted to 20W,and the second CNB could be performed after the ablation radius exceeded 0.5cm of the original GGN lesion radius detected by CT,that is,microwave ablation coagulation(MTC).After the biopsy,the power was adjusted to between 40 and 65W to continue the MWA inactivation of GGN.After the surgery,the 16G puncture needle and MWA antenna were removed,and the puncture site was covered with sterile dressing.All patients were required to be hospitalized for observation for at least 24 hours.In this paper,after pathological examination of the patient’s pathological specimens,the following pathological results were found:AAH,AIS,MIA,IAC,inflammation and lung tissue.After ablation,CNB tissue was deformed with physical damage and burning.Treatment-related complications were defined as those occurring within 30 days of surgery.Severity is graded according to standards set by the American Society of Interventional Radiology(SIR).Statistical analysis was performed using SPSS 17.0(IBM,Chicago,USA).To compare the positive rates of CNB before and after MWA,we applied the Mcnemar Chi-square test.P<0.05 was considered statistically significant.Results:A total of 74 GGN lesions from 74 patients were included in this study.Of the 74 patients.36(48.6%)were male,and 38 were over 60 years old.The upper lobe of the right lung was the most common location(27,36.5%).Pure GGN nodules were dominant(55.74.3%),and the average diameter of GGN was 17.1mm.The mean ablation power was 57.6W and the mean ablation time was 6.9min.The mean postoperative hospital stay was 3.4 days.Pathological results of CNB before MWA included AAH(n=4),AIS(n=16),MIA(n=14),IAC(n=29),chronic inflammation(n=2),and lung tissue(n=9),with a positive rate of 85.1%(63/74).Pathological results of CNB after MTC included:AAH(n=5),AIS(n=10),MIA(n=11),AC(n=29),chronic inflammation(n=1),and lung tissue(n=18),the positive rate was 74.3%(55/74).In two patients,the pathological results of CNB before ablation were MIA(n=1)and IAC(n=1),but the pathological results of CNB after MTC were AAH.Based on the definition of positive group,the pathological results of CNB after MTC were also defined as positive group.According to McNemar’s Chi-square test,there was no statistical difference in the positive rate of CNB pathological results before MWA and after MTC(P=0.077),and the positive rate of biopsy after ablation was not inferior to that of biopsy before ablation.The final pathological results were the comprehensive pathology of CNB before and after ablation,including AAH(n=4),AIS(n=16),MIA(n=16),AC(n=31),chronic inflammation(n=2),and lung tissue(n=5),with a positive rate of 90.5%(67/74).Mcnemar Chi-square test showed that the positive rate of final pathological diagnosis was higher than that of post-MTC biopsy(P<0.001),and there was no difference between the positive rate of final pathology and pre-MWA CNB biopsy(P=0.125).Therefore,the significance of pre-MWA biopsy should not be ignored.In 4 patients,the pathological result of CNB before MWA was lung tissue,but the pathological result of CNB after MTC was MIA(n=2)or IAC(n=2).The positive group was the sum of AAH,AIS,MIA and IAC.Due to the limited biopsy tissue,the pathology before ablation was adenocarcinoma,and the pathology after ablation was atypical adenomatoid hyperplasia.Therefore,the positive rate was defined as(AAH+AIS+MIA+IAC)/67,while the diagnosis rate was defined as:The diagnosis consistent with the final pathological result/67,so the diagnostic rate of biopsy before ablation was 94.0%,which was higher than that of biopsy after ablation(79.1%).The diagnostic rate of biopsy before ablation was higher than that of biopsy after MTC(P<0.001).Biopsy before ablation still plays an important role in the pathological diagnosis of patients.In this study,the mortality rate within 30 days after surgery was 0%.The main adverse reactions were pneumothorax.Patients requiring thoracic puncture and catheter drainage accounted for 14.9%of all patients(n=11),and 34 patients(45.9%)had a small amount of pneumothorax,which did not require thoracic puncture and catheter.Conclusion:The positive rate of biopsy after ablation is not inferior to that of biopsy before ablation,which is of great significance for the diagnosis of GGN pathology.