| Part I Drug-Eluting Bead Bronchial Arterial Chemoembolization With and Without Microwave Ablation for the Treatment of Advanced and Standard TreatmentRefractory/Intolerant Non-Small Cell Lung Cancer:A Comparative StudyPurpose:To compare the outcomes of drug-eluting beads bronchial arterial chemoembolization(DEB-BACE)with and without microwave ablation(MWA)for the treatment of advanced and standard treatment-refractory/intolerant non-small cell lung cancer(ASTRI-NSCLC)without oncogene mutants,and to explore the efficacy and safety of combination regimens for these patients.Materials and Methods:A total of 92 ASTRI-NSCLC patients without oncogene mutants were included,and were allocated to DEB-BACE combined with MWA(group A;n=31)or DEB-BACE alone(group B;n=61).Adverse events(AEs)and outcomes were compared between the two groups.Kaplan-Meier methods were used to compare the median progression-free survival(PFS)or overall survival(OS)between the two groups.Univariate and multivariate Cox proportional hazards analyses were used to investigate the prognostic predictors of DEB-BACE for ASTRI-NSCLC without oncogene mutants.Results:A significant difference was found in the incidence of hypertension(P=0.029),whereas other variables revealed no differences.Pneumothorax was the predominant MWArelated AEs in group A,with an incidence rate of 32.3%(10/31).No significant difference was found in overall AEs between groups A and B(P=0.202).Meanwhile,no severe AEs(SAEs)were found in both groups.The median PFS in groups A and B was 9.0 and 4.0 months,respectively,and the median OS in groups A and B was 15.0 and 9.0 months,respectively.Kaplan-Meier methods revealed a higher median PFS(P=0.006)and OS(P=0.021)in group A,and a higher disease control rate(DCR;83.9%vs 57.4%,P=0.011)was also found in group A.Regarding the efficacy of DEB-BACE in ASTRI-NSCLC patients without oncogenes mutant,univariate and multivariate analyses revealed that tumor diameter≥6cm([hazard ratio],HR:1.755;95%[confidence interval,CI]:1.083-2.844;P=0.022)and tumor number≥2(HR:2.240;95%CI:1.165-4.308;P=0.016)were the negative predictors for PFS,and combination therapy of MWA(HR:0.433;95%CI:0.2550.735;P=0.002),cycles of DEB-BACE/bronchial artery infusion(BAI)≥2(HR:0.607;95%CI:0.375-0.984;P=0.043)and postoperative immunotherapy(HR:0.425;95%CI:0.247-0.730;P=0.002)was the positive predictor of PFS,while tumor diameter≥6cm(HR:1.789;95%CI:1.086-2.949;P=0.022)was the negative predictors for OS,and combination therapy of MWA(HR:0.559;95%CI:0.317-0.984;P=0.044),cycles of DEB-BACE/(BAI≥2(HR:0.500;95%CI:0.303-0.826:P=0.007)and postoperative immunotherapy(HR:0.391;95%CI:0.213-0.715;P=0.002)were the positive predictors for OS.Conclusion:Compared to DEB-BACE alone,combination therapy of DEB-BACE and MWA could improve the PFS and OS of ASTRI-NSCLC without oncogene mutants.MWA sequentially combined with DEB-BACE are effective and safe approaches for these patients,and postoperative immunotherapy may predict a better prognosis.Part II Tyrosine kinase inhibitors With and Without MWA for the Treatment of Advanced and Treatment-naive Non-Small Cell Lung Cancer harboring Epidermal Growth Factor Receptor Mutants:The Intermediate ResultsPurpose:To compare the intermediate outcomes of MWA plus epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)versus EGFR-TKIs alone for advanced and treatment-naive NSCLC harboring EGFR mutants,and to explore the efficacy and safety of combination therapy for these patients.Materials and Methods:A total of 117 advanced and treatment-naive NSCLC patients harboring EGFR mutants were included,and were allocated to MWA combined with EGFR-TKIs(group A;n=43)or EGFR-TKIs alone(group B;n=74).AEs and outcomes were compared between the two groups.Kaplan-Meier methods were used to compare the median PFS or OS between the two groups.Univariate and multivariate Cox proportional hazards analyses were used to investigate the predictors of PFS and OS for advanced and treatment-naive NSCLC patients harboring EGFR mutants treated with EGFR-TKIs.Results:No significant differences were found in baseline characteristics and TKIs details.Pneumothorax was the predominant MWA-related AEs in group A,with an incidence rate of 20.9%(9/43).No significant difference was found in overall AEs between the two groups(P=0.776),and the incidence rate of SAEs was 10.3%(12/117).In a mean follow-up of 37.6±17.9 months,the median PFS in groups A and B was 18.0 and 10.0 months,respectively,and the median OS in groups A and B was 24.0 and 25.0 months,respectively.Kaplan-Meier methods revealed a higher median PFS(P<0.001)in group A but a similar median OS(P=0.083)in the two groups.When compared to group B,group A revealed a lower local progression rate(25.6%vs 52.7%,P=0.004),and higher one-year and two-year PFS rates(72.1%vs 32.4%,P<0.001;27.9%vs 9.5%,P=0.009)and a higher survival rate(44.2%vs 17.6%,P=0.002).Regarding the efficacy for advanced and treatment-naive NSCLC patients harboring EGFR mutants treated with EGFR-TKIs,univariate and multivariate analyses revealed that higher tumor stage(HR:2.181;95%CI:1.177-4.044;P=0.013)was the negative predictor of PFS and combination therapy with MWA(HR:2.133;95%CI:1.395-3.262;P<0.001)were the positive predictors of PFS,while higher tumor stage(HR:3.483;95%CI:1.588-7.639;P=0.002)was the negative predictor of OS,and third-generation EGFR-TKIs(HR:0.482;95%CI:0.312-0.747;P=0.001)was the positive predictor of OS.Conclusion:MWA sequentially combined with EGFR-TKIs are effective and safe approaches for advanced and treatment-naive NSCLC harboring EGFR mutants.Intermediate results reveal that the combination regimens are superior to EGFR-TKIs alone in the local control.Although combination therapy reveals a trend of prolonging the OS,the advantage was not significant due to limited follow-up time,and whether combination therapy could benefit patients with longer OS needed further investigation.Part Ⅲ Multi-model Comprehensive Interventional Therapies for Advanced Nonsmall Cell Lung Cancer Based on Drug Tests of Patient-derived Tumor-like Cell Cluster:A Pilot Study of 17 CasesPurpose:To explore the feasibility of patient-derived tumor-like cell cluster(PTC)culture and drug-sensitive tests based on specimens from percutaneous lung biopsy,and to investigate the efficacy and safety of multi-model comprehensive interventional therapies for advanced NSCLC based on drug-sensitive tests of PTC.Materials and Methods:All the patients received percutaneous lung biopsy to undergo pathology,genetic tests,and PTC drug tests,and concomitant MWA was performed to inactivate the tumor as much as possible,followed by sensitive TKIs for oncogene-mutant patients or sensitive DEB-BACE/BAI combined with programmed cell death protein 1(PD1)blockade for oncogene-wild patients based on the results of PTC drug tests.AEs were analyzed and Kaplan-Meier methods were used to analyze the PFS and OS for these patients.Results:A total of 27 patients performed PTC culture and drug-sensitive tests,with positive culture rates of 77.8%(21/27).The number of drug regimens that can be tested was 6.0 ±2.5.PTC drug-sensitive tests showed that the percentage of anti-tumor cells for the most effective drug regimens was 34.0 ± 20.2%.Finally,17 unresectable or chemo-radiotherapy refractory/intolerant advanced NSCLC patients were included.The age of these patients was 66.4 ± 11.6 years,and 76.5%(13/17)of the patients were stage Ⅲ.Adenocarcinoma was the predominant tumor subtype(70.6%,12/17).Sequential treatments were conducted according to the genetic analyses and PTC drug tests.There were six patients(35.3%)who underwent sensitive TKIs,including four patients(23.5%)who administered Osimertinib and two patients(11.8%)who administered Crizotinib;there were 11 patients(64.7%)who underwent sensitive DEB-BACE/BAI plus PD-1 blockade,of these,six patients(35.3%)were administered by platinum and gemcitabine.The incidence rate of SAEs was 11.8%(2/17),consisting of 5.9%for bronchopleural fistula and 5.9%for immune enteritis.In a mean follow-up of 10.8±4.4 months,the DCR was 94.1%,and the median PFS and OS were not reached.PTC drug tests revealed an overall accuracy of 94.1%in predicting efficacy.Conclusion:The specimens based on percutaneous lung biopsy were effective for PTC culture and drug tests.Multi-model comprehensive interventional therapies based on drug tests of PTC may be effective and safe for advanced NSCLC,and revealed an overall accuracy of 94.1%in predicting efficacy. |
PDF Full Text Request