Clinical And Experimental Research On Cold Ablation Combined With Traditional Chinese Medicine In The Treatment Of Elderly Patients With Advanced Non-small Cell Lung Cancer

[Research background]Elderly advanced nonsmall-cell lung cancer(NSCLC,nonsmall-cell lung cancer)has extremely high morbidity and mortality.For patients with negative driver genes,chemotherapy is the first choice recommended by the guidelines,but many elderly patients with advanced NSCLC The body reserves are poor and cannot be chemotherapy,or cannot tolerate the side effects of chemotherapy and the treatment is interrupted.In some patients,the effect of chemotherapy is average,and progress is soon after chemotherapy,so the treatment methods are relatively limited.The "cold ablation combined with traditional Chinese medicine" treatment mode is guided by TCM theory,with TCM syndrome differentiation as the main line,and cold ablation minimally invasive treatment as the key node.It has the characteristics of low damage and sustainability.Many previous research conclusions show that the clinical effect of cold ablation combined with traditional Chinese medicine is better.However,there are few studies on the specific population of elderly patients.Whether the therapeutic effect of cold ablation combined with traditional Chinese medicine can reach the level of conventional chemotherapy and whether it can be advanced in the elderly New treatment options for NSCLC patients,especially those who are unable to undergo chemotherapy or whose chemotherapy effects are not effective,require further evaluation.At the same time,by summarizing the characteristics of the "superior population" of this model,the postoperative treatment and treatment of patients with cold ablation combined with traditional Chinese medicine are studied The prescription and the mechanism of action are expected to further optimize the treatment model and increase patient benefits.[Research objective]Clinical part:1.To evaluate whether the efficacy of cold ablation combined with traditional Chinese medicine in the treatment of elderly patients with advanced NSCLC can reach the level of conventional chemotherapy.Treatment options for injuries;2.Summarize the characteristics of the "superior population" of the cold ablation combined with traditional Chinese medicine treatment model to provide reference for clinical decision-making;3.Study the changes in TCM syndrome elements and the rule of treatment methods before and after the operation of the cold ablation combined with traditional Chinese medicine cohort,Explore the characteristics of TCM syndrome changes and applicable prescriptions after cold ablation,with a view to optimizing the model to improve the treatment effect.Experimental part:1.To evaluate the efficacy of cold ablation combined with traditional Chinese medicine compared with chemotherapy,simple cold ablation and traditional Chinese medicine intervention in elderly lung cancer mice;2.Based on immune regulation and angiogenesis to study the mechanism of cold ablation combined with traditional Chinese medicine intervention in elderly lung cancer mice.[Research content]Clinical part1.Propensity score matching baseline information:Based on multicenter real-world treatment data for lung cancer,316 samples were included and divided into cold ablation combined with traditional Chinese medicine cohort and chemotherapy cohort,using propensity score matching method to reduce confounding factor matching 87 pairs;2.Survival Analysis:Comparing the median OS,median PFS and survival rate of the two cohorts,and COX regression to screen independent prognostic factors;3.Screening the"dominant population":using Logistic regression to analyze the characteristics of the dominant population of the two treatment methods;4.Evaluate the efficacy and safety Properties:To evaluate the efficacy of solid tumors in the two cohorts,objective remssion rate,disease control rate,KPS score,and adverse reactions.5.Research on the distribution of TCM syndrome elements and the rule of prescription:study the distribution of syndrome factors before and after cryosurgery in the cold ablation combined with TCM cohort and the rule of prescription medication;Experimental partthe experimental part The experiment is divided into two parts:experiment one and experiment two.1.Grouping:40 and 45 old Lewis lung cancer model mice were divided into ? model group,?combined cold ablation combined with Chinese medicine group,?cold ablation group,?chemotherapy group,?Chinese medicine group.2.Intervention:?Only modeling in the model group,?Cryoablation surgery×1 time and Xing xiao pill solution gavage 1 time/day×14 days,?Cryoablation surgery×1 time,?Intraperitoneal injection of cisplatin 3mg/kg×1 time/weekx2 weeks,?Xing xiao pill solution was intra gastrically administered once/day×14 days;the body weight of mice was recorded the next day and the tumor diameter was measured.In addition,the non-Chinese medicine intervention group was given normal saline intragastric administration without chemotherapy intervention The group was given intraperitoneal injection of normal saline,and the non-cold ablation intervention group was given an incision and suture.3.Indicators:Experiment 1 observes the survival period;Experiment 2 calculates the organ index of mouse spleen and thymus,tumor growth/metastasis inhibition rate,flow cytometric detection of mouse spleen tissue CD4+,CD8+,CD4+/CD8+ratio;ELISA detection is small The expression of IFN-y,IL-2 and IL-10 in mouse serum;WB was used to detect the expression of HIF-1?,VEGF,MMP-2 and MMP-9 in mouse lung and tumor tissues.[Research results]Clinical part1.The cold ablation combined with Chinese medicine cohort(hereinafter referred to as the"combined cohort")and the chemotherapy cohort were enrolled in 96 and 220 cases,respectively.The propensity score matched 87 pairs.The median OS of the two groups was 13 months and 10.3 months,respectively(P>0.05).There was no significant difference in survival rates of 6 months,1 year,2 years,and 3 years between the two groups(P>0.05).2.After matching,the median PFS of the combined cohort and chemotherapy cohort were 4.7 months and 4 months(P<0.05),and the 6-month progression-free survival rate was 34.2%and 18.4%(P<0.05),respectively.Patients in the combined cohort the chance of PFS>6 months is three times that of the chemotherapy cohort.3.Analysis of independent influencing factors of survival:?Combined cohort,LY%is an independent protective factor,CCI and clinical stage are independent risk factors.?In the chemotherapy cohort,LY%and KPS are independent protective factors,and NEUT%,KPS,CCI,NLR and clinical stage are independent risk factors.4.Advantage population characteristics:?Advantage population characteristics of the cold ablation combined with traditional Chinese medicine cohort in this study:age ?80 Age and the advantage is negatively correlated with age;CCI score ?9;LY%>20%for stage ?b,?c,and ?a.?The characteristics of the superior population in the chemotherapy cohort:the earlier clinical stage,the most obvious advantage in stage ?b;NLR?3.3;KPS?80 points.5.KPS score:KPS of cold ablation combined with traditional Chinese medicine cohort after treatment>KPS of chemotherapy cohort(P<0.05).6.Evaluation of the efficacy of solid tumors:the disease control rate of the combined cohort was 26.83%>the chemotherapy cohort 13.79%(P<0.05).7.The disease location syndrome factors are mainly lung,spleen and kidney;disease syndrome factors are mainly qi deficiency,yang deficiency,and yin deficiency,and the evidence is mainly blood stasis,phlegm dampness,and postoperative blood stasis and yang deficiency syndrome factors are significantly increased(P<0.05);Astragalus,Schisandra,etc.for nourishing qi;Ophiopogon japonicus and rehmannia for nourishing yin;Poria and Atractylodes atractylodes for invigorating the spleen and kidney;Asarum,dried ginger,etc.to warm Yang and dispel cold;Frankincense,Myrrh,Panax notoginseng It promotes blood circulation and removes blood stasis;Pinellia,dried tangerine peel and other dampness;Chuan Fritillaria,Zhejiang Fritillaria,etc.clear heat.8.New recipe combinations:?Frankincense,Myrrh,Dried Ginger,Asarum;? Red Peony,Safflower,Asarum,Dried Ginger,Schisandra;? Peach Kernel,Red Peony,Safflower,Asarum,Dried Ginger,which reflects warmth To promote blood circulation and remove blood stasis treatment.Experimental partExperiment 1 The average survival time of mice in the cold ablation combined Chinese medicine group(hereinafter referred to as the "combination group")was 28 days,which was significantly higher than 19 days in the model group and 22.5 days in the chemotherapy group(P<0.05).Experiment 21.Body weight:The body weight of the mice in the chemotherapy group was significantly lower than that of the model group(P<0.05);the body weight of the mice in the combination group,cold ablation group and traditional Chinese medicine group was significantly higher than that of the chemotherapy group(P<0.05)2.Tumor mass:The tumor mass of mice in the combined group,cold ablation group,and chemotherapy group was smaller than that of the traditional Chinese medicine group and the model group(P<0.05).3.Lung metastasis inhibition rate:the number of lung metastasis nodules in the combined group,cold ablation group and chemotherapy group was less than that of the model group(P<0.05),and the number of lung metastasis nodules in the cold ablation group,chemotherapy group and traditional Chinese medicine group was more than that in the combined group Group(P<0.05).4.Organ index:The spleen index and thymus index of mice in each group were higher than the model group(P<0.05);the spleen index and thymus index of the cold ablation group,chemotherapy group and traditional Chinese medicine group were lower than the combination group(P<0.05).5.Flow cytometry detection:the expression of CD4+in the combination group and the cold ablation group was higher than that of the model group(P<0.05);the expression of CD4+in the spleen tissue of mice in each group was lower than the combination group(P<0.05);The expression of CD8+in the group was lower than that in the model group(P<0.05);the CD4+/CD8+in the spleen tissue of mice in each group was lower than the combination group(P<0.05);the combination group and the cold ablation group had CD4+/CD8+>1.6.ELISA detection6.1 IL-2:combination group,cold ablation group,chemotherapy group>model group(P<0.05);combination group>cold ablation group,chemotherapy group and traditional Chinese medicine group(P<0.05).6.2 IL-10:the expression of IL-10 in each group<model group(P<0.05);combination group<cold ablation group,chemotherapy group and traditional Chinese medicine group(P<0.05).6.3 IFN-?:the expression of IFN-? in each group>model group(P<0.05);chemot herapy group and traditional Chinese medicine group<combination group(P<0.05);col d ablation group>chemotherapy group,traditional Chinese medicine group(P<0.05);7.Western Blot detection7.1 VEGF and HIF-1? ?Lung tissue:VEGF and HIF-1? expression in each gro up<model group(P<0.05);mouse VEGF expression in each group>combination grou p(P<0.05);cold ablation HIF-1? expression in lung group and traditional Chinese me dicine group>combined group(P<0.05),HIF-la expression in traditional Chinese medic ine group>cold ablation group(P<0.05).?Tumor tissue:the expression of VEGF and HIF-1? in each group<model group(P<0.05);the expression of VEGF in each group>combined group(P<0.05).The expression of HIF-la in each group>the combined group(P<0.05).7.2 MMP-2 and MMP-9?Lung tissue:MMP-2:MMP-2 expression of mice in each group<model group(P<0.05);combination group<other groups(P<0.05).MMP-9:combination group,cold ablation group and chemotherapy group<model group(P<0.05);traditional Chinese medicine group>combination group(P<0.05).?Tumor tissue:MMP-2:combination group,cold ablation group and chemotherapy group<model group(P<0.05).MMP-9:combination group,cold ablation group and chemotherapy group<model group(P<0.05);traditional Chinese medicine group>combination group(P<0.05).[Conclusions]1.For elderly patients with advanced non-small cell lung cancer without gene mutations,cold ablation combined with traditional Chinese medicine therapy is superior to conventional chemotherapy in terms of delaying disease progression,enhancing short-term efficacy,and improving the quality of life of patients,and in terms of overall survival benefits It is equivalent,so it can be used as a treatment option for elderly patients with advanced NSCLC,especially those who cannot be treated with chemotherapy or whose chemotherapy is not effective.2.Age<80 years old,CCI score ?9,tumor clinical stage is ?b,?c,?a,LY%>20%of elderly patients with advanced NSCLC are more suitable for cold ablation combined with traditional Chinese medicine treatment.3.Cold ablation combined with traditional Chinese medicine model for the treatment of advanced NSCLC in the elderly.The main line of treatment is to replenish qi,nourish yin,warm yang,nourish the lung,invigorate the spleen,and reinforce the kidney,and take into account the different stages of promoting blood circulation and removing blood stasis,removing dampness and removing phlegm,etc.Evil treatment,meanwhile,yang deficiency and blood stasis syndrome are common in elderly patients with advanced NSCLC,especially patients after cold ablation.The treatment should pay attention to the treatment of warming,promoting blood circulation and removing blood stasis.4.The combination of cold ablation combined with Wentong Huoxue Huayu therapy has a better effect in prolonging survival time and inhibiting metastasis.Its mechanism is related to promoting anti-tumor immunity and inhibiting tumor angiogenesis.