Evaluation Of Curative Effect Of Chinese Medicine Combined With Cold Ablation In The Treatment Of Primary Lung Cancer And Study Of Dominant Populations

[Background]Primary lung cancer is a type of malignant tumor with highest incidence and mortality.The molecule-targeted treatment,which plays a significant role in treating advanced non-small cell lung cancer,has become the first-line therapy recommended by NCCN due to the fact that it can prolong the survival of patients with driver mutation.However,those patients with driver mutation merely takes a small portion.Are there other appropriate options for the rest of patients,whose median survival time is estimated to be 8to 10months,apart from standard chemoradiotherapy?Traditional Chinese medicine combined with cryoablation for primary lung cancer is an innovative development model that combines traditional Chinese medicine diagnosis and treatment technology with modern science and technology.During this process,Chinese and Western complement each other and the past is well utilized to serve the present.In the past 15 years,this "mild"and "non-standard"treatment model has been continuously optimized and gradually developed into a green therapeutic model for cancer.Although cryoablation is a common treatment for lung cancer at home and abroad,can the combination of traditional Chinese medicine on this basis benefit us more?Or under what circumstances will it be more appropriate?Where can we find the driver-mutation-positive patients of Chinese Medicine Combined with cryoablation Therapy?What are the characteristics of these dominant groups?Additionally,non-small cell lung cancer(NSCLC)accounts for 85%of all lung cancers,and the vast majority of patients were found when they are already in the advanced stage.Most patients are in stage ?b-?,driver-mutation-negative and advanced non-small cell lung cancer which is unsuitable for surgery.The NCCN guidelines recommend chemotherapy as its standard treatment,but the response rate of chemotherapy is only 20-30%.Therefore,for the remaining nearly 70%of patients,can some not be treated by chemotherapy?What characteristics of patients can not be treated with chemotherapy?If not,what are the other options they might have?[Objectives]1.By reviewing the data of lung cancer patients treated with TCM combined with cryoablation in our hospital in the past 15 years(from September 2003 to March 31,2018),we evaluated the clinical efficacy and established a preliminary prognostic prediction model,which was used to screen the dominant population and extract the characteristics of the dominant population,so as to provide reference for doctors and patients in choosing treatment.2.To compare the survival differences of patients with stage IIIB-IV non-small cell lung cancer treated with traditional Chinese medicine combined with cryoablation(simple treatment group)and traditional Chinese medicine combined with cryoablation combined with chemotherapy(combined treatment group),and to analyze the characteristics of dominant groups in simple treatment group.[Methods]1·The first study is a retrospective clinical study.The ultimate goal is to select the dominant population via screening the patients with primary lung cancer who are treated with Chinese herbal medicine combined with cryoablation and to evaluate the efficacy of such therapeutic pattern on patients' survival.The survival differences of patients with different pathology,stages and treatment groups are compared.The survival scores of patients with different groups are regression by single factor method and COX.Preliminary prognostic prediction model was established by screening out independent risk factors.The accuracy of the model was verified by various methods to analyze the clinical characteristics of the dominant population.2.The second study,on the basis of the previous one,included the patients in study one who met the criteria of "non-small cell lung cancer,stage ?B-IV,cryoablation alone with traditional Chinese medicine or combined cryoablation with chemotherapy with traditional Chinese medicine".They were divided into two groups:simple treatment group and combined treatment group.The differences in survival between the two groups were compared,and the characteristics of dominant groups in the simple treatment group were analyzed.[Results]1.The cryoablation in this study is a traditional Chinese medicine surgical technology under the guidance of TCM surgical thoughts.The ablation needle used is a new"nine needles"with TCM cold and heat attributes.It follows the TCM surgical principles of "direct access to the sick place","cut first and then pull out".It also conforms to the TCM principles of "to treat heat with cold","to go against the scarcity,and to abide by what is too much ","when severe toxicity is used as a treatment of the disease,six out of ten will be healed...If not enough,follow the law again".It is of great significance to explore the cryoablation under the guidance of TCM theory.2.Case Screening:Through multi-system case screening and follow-up investigations,1359 cases of cold ablation in our hospital in the past 15 years were screened,including 521 cases of primary lung cancer(481 cases of lung cryoablation,40 cases of non-lung cryoablation),641 cases of cryoablation(599 cases of lung cryoablation,42 times non-lung);112 patients(119 times)who met the exclusion criteria were excluded and 116 patients were lost to follow-up.Eventually 293 patients(371 times of cold ablation)were involved,including 29cases of small cell lung cancer,264 cases of non-small cell lung cancer.Up to now the number of survivors is35.3.Overall study results of all patients:The subjects in this study were mainly middle-aged and elderly,male,with more basic diseases,advanced stage,non-small cell lung cancer and lung cryoablation;the median total survival time was 14.33 months,OR 0.86,95%CI(12.64-16.02);the median total survival time after operation was8.37 months,OR 0.7,95%CI(7.00-9.74);in terms of safety evaluation,the parameters of cold ablation were relatively mild.And the four most common complications were hemoptysis(48.6%),fever(42.3%),cough(36.7%),pain(32.6%).The duration was short,the symptomatic treatment was quickly relieved,and the overall clinical tolerance was good.4.Research results on non-small cell lung cancer4.1A total of 264 cases(332 times)of non-small cell lung cancer were involved in this study.The majority of the population included shared such features:middle-aged or old,male,suffering from more basic diseases,advanced stage,poorly differentiated,adenocarcinoma and deficiency syndrome.The median overall survival time was 13.87 months,OR 1.04,95%CI(11.83-15.91),median postoperative survival time was 8.3 months,OR 0.65,95%CI(7.03-9.56).The survival rates after 6months,1,2,3 and 5years were 84.10%,55.20%,32.60%,17.80%and 5.5%respectively.4.2 Preliminary prognostic prediction model and dominant population:According to the model score,the model was divided into three groups:low-risk group(especially recommended),medium-risk group(recommended)and high-risk group(cautiously decided).Three methods were used to validate the model,and the accuracy rate was around 80%.The median survival time after operation of low-risk group(108 cases)was 16.53 months,which was the dominant group in this study.Characteristic analysis showed that whether the model was consistent with Mlc.target lesion size,neutrophil to lymph ratio and fibrinogen content can better reflect the characteristics of the dominant population.Among them,whose"preoperative diagnosis does not conform to Mlc,preoperative neutrophil to lymph ratio is less than 2.34,preoperative fibrinogen content is less than 3.22,and target lesion size is less than 35 mm" is the best prognostic group.5·Research results on small cell lung cancer5.1In total,29 cases of small cell lung cancer(39 times)were involved in this study.The majority of the population included shared such features:middle-aged or old,male,suffering from more basic diseases,extensive period,high smoking index and deficiency syndrome.The median overall survival time was 20.27 months,OR 1.94,95%CI(16.46-24.08),median post-operative survival time was 9.13 months,OR 2,16,95%CI(4.90-13.36).The survival rates after 6 months,1,2,3,5 years were 89.7%,68.5%,39.7%,21.6%and 9.0%respectively.5.2 Preliminary model of prognosis prediction and predominant population:According to the model score,the patients were divided into three groups:low-risk group(especially recommended),medium-risk group(recommended),high-risk group(cautiously decided).Because the sample size is rather small,the validation of extra-sample model could not be completed for the time being whereas the methodological exploration was the main method.The median survival time after operation of low-risk group(13 cases)was 14.27 months,which was the predominant group in this study.Characteristic analysis showed that "preoperative diagnosis of M stage and neutrophil-lymphocyte ratio"could reflect the characteristics of the dominant population,and "patients with preoperative M stage of MO and neutrophil-lymphocyte ratio<1.68" was the best prognostic group in this study.6.Controlled study of stage III b-IV non-small cell lung cancer6.1A total of 130 eligible patients were involved in the treatment group:104 in the single treatment group and 26 in the combined treatment group.The baseline of the two groups was comparable.The groups mainly included middle-aged or elderly,male,with more basic diseases,stage IV,poorly differentiated,adenocarcinoma,high smoking index and deficiency syndrome.The median overall survival time of the treatment group was 11.13 months,95%CI(8.91-13.35),and that of the combined treatment group was 8.57 months(P=0.7).6)There was no statistical difference between them.6.2 Predominant population:The patients whose total survival time>10months in the simple treatment group were selected as the dominant group(55cases/52.88%).Characteristic analysis showed that the earlier the initial M stage was,the better the prognosis was.The best prognostic population of the dominant group was"also indicate a good prognosis trend,which can be further studied after enlarging the sample size.Characteristic analysis showed that"patients with early initial M stage?early preoperative M stage and preoperative non-Mlc,neutrophil lymphocyte ratio<3.30,lymphocyte percentage>20.00,KPS score>80.Mononuclear lymph ratio<0.48"could reflect the characteristics of the dominant population.[Conclusion]1.The cryoablation in this study is the product of the continuous optimization and development of "Nine Needles"through modern material civilization.It has its clear guiding ideology and technical origin of traditional Chinese medicine surgery.2.Traditional Chinese medicine combined with cryoablation is safe and effective in treating primary lung cancer.Screening the dominant population is helpful to prolong the survival time of patients after operation significantly.3.The accuracy of the preliminary prognostic prediction model for non-small cell lung cancer is relatively high,which can be further validated and perfected in high-level clinical trials in the future.Some parameters can better reflect the characteristics of the predominant population of non-small cell lung cancer in this study:"whether it conforms to Mlc,target lesion size,neutrophil-lymphocyte ratio,and fibrinogen content".4.The treatment mode of Chinese medicine combined with argon-helium knife for limited-stage small cell lung cancer patients deserves further study;"Preoperative diagnosis of M stage,neutrophil-lymph ratio" can preliminarily summarize the characteristics of the dominant population of small cell lung cancer in this study.5.There is no statistical difference between the simple treatment group and the combined treatment group,which fails to reflect the superiority of the combined treatment group.For stage ?B-?,driver gene negative,deficiency syndrome advanced non-small cell lung cancer patients,the simple use of Chinese medicine combined with cryoablation therapy requires further study." initial M stage,preoperative M stage,preoperative non-M1c,neutrophil lymphocyte ratio,lymphocyte percentage,KPS score,Mononuclear lymph ratio" can summarize the characteristics of the dominant group in the simple treatment group in this study.