| Part1:Clinic Research of Simultaneous Integrated Boost Intensity Modulated Radiotherapy in Locally Advanced Non-small Cell Lung CancerObjective:Simultaneous integrated boost intensity modulated radiotherapy could simultaneously confer a radical dose to the gross tumor while a relatively lower dose to the subclinical disease.Currently,the efficacy and toxicity of SIB-IMRT remains unclear in locally advanced non-small-cell lung cancer(LA-NSCLC).Therefore,we conducted a retrospective analysis to explore the efficacy and tolerance of SIB-IMRT for patients,as well as the dosmetric advantages in terms of organ at risks protection.Methods:Patients who had histologically confirmed NSCLC,stage Ⅲ disease and received thoracic IMRT between 2014 and 2016 were retrospectively reviewed.The OS,PFS,LRFS and DMFS was analyzed using Kaplan-Meier method.Chi-square test was used for toxicity data comparison between groups.Dose to OARs were compared by using the Mann-Whitney U test.Forty patients were randomly selected for automated planning.Both SIB-VAMT and conventional VMAT plans were generated for each patient using the script of autoplan 2.0 and the OARs doses were compared between two groups.The prescribed dose was 50.4Gy in 28 fractions to PTV and 59.92Gy in 28 fractions to PGTV in SIB plans,with 60Gy in 30 fractions to PTV in conventional plans.Results:A total of 426 patients with stage Ⅲ NSCLC were eligible for analysis,including 128 with SIB-IMRT and 298 with conventio nal IMRT.with median follow-up time of 26.35 months.SIB-IMRT group had more stage ⅢB disease(69.5%vs.53%,P=0.002).larger planning treatment volumes(median:504 ml vs.402 ml,P<0.001).and a larger planning treatment volume/volume of lung ratio(median,0.18 vs.0.12,P<0.001).The median OS of the SIB-IMRT and conventional IMRT groups were 28.9 and 29.6 months,with the 3-year rate of 44%and 42%,respectively(P=0.998).No difference in PFS.LRFS,DMFS or treatment-related toxicity was observed between the two techniques.The local-regional recurrence rates were 37.5%and 39.6%,respectively(P=0.684).The multi-variables analysis indicated that KPS(HR0.51,95%CI[0.302-0.859].P<0.004)、PTV vomlue(HR 1.515.95%CI|1.151-1.994],P<0.001)and concurrent chemoradiotherapy(HR 0.532,95%CI[0.408-0.692],P<0.001)were independent factors affecting OS.The automated SIB-VMAT conventional VMAT plans were compared.and the results indicated that SIB plan got lower lung MLD,V30.V40 and V50 than conventional plan.with median decreased proportion of 6.5%、8.7%、9.6%and 32.1%.The SIB plans also got lower heart V30 and V40 than conventional plans,with median decreased proportion of 26.1%and 38.8%.Besides,the sharp reductions in heart were observed in cord maximal dose and esophageal maximal dose.with median decreased proportion of I 4.7%and 7.2%.Conclusions:SIB-IMRT might be an effective and safe option for patients with locally advanced NSCLC and It offered patients with large tumor volume or wide lymph node metastasis the chance to receive a more intense treatment.The dose-reducing for subclinical disease did not result in increased recurrence risk.SIB-VMAT plan yielded full protection for normal tissues,with significant reduction in the doses to organ at risks.Future prospective evidence is warranted to confirm the efficacy of SIB-IMRT in NSCLC patients.Part2:Translational Research of Prognostic Biomarkers Based Screening on Metabolomic Profiling in Locally Advanced Non-small Cell Lung CancerObjective:The role of metabolomic profiling in the diagnosis and efficacy prediction for NSCLC remains unclear.This study aimed to explore potential biomarker that could predict the long-term overall survival for locally advanced non-small cell lung cancer based on serums Metabolites detection.Methods:145 patients with NSCLC and 155 healthy persons were enrolled in the study.Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC-MS/MS.The chromatographic and mass spectral data were converted into a two-dimensional matrix using the software of XCMS.Independent samples t test was used to identify the significantly changed metabolites between groups.Tbe type and structure of biomarkers were identitied with the methods of high resolution mass spectrometry.library searching and standard comparision.The patients receiving curative radiotherapy were selected form the 145 patients,and the data collection and follow-up were finished.X-title was used to identify metabolites that had association with overall survival and its cutoff points.Graphpad Prism 7.0 was applied for imaging and SPSS 20.0、R 3.6.2 for statistical analysis.SurvivalROC was performed to evaluate the predictive model.P<0.05 was considered statistically significant.Results:105 metabolites were identified after serum test for lung cancer patients and healthy people.including lysophosphatidycholine.sphingomyelin,steroids hormone,carnitine and so on.58 metabolites were up-regulated and 47 were down-regulated in lung cancer patients compared to healthy group.There are 17 patients diagnosed as stage Ⅱ-Ⅲ receiving definitive radiotherapy.The 1,2 and 3-year overall survival were 72%,58%and 50%,respectively.Seven metabolites were significantly correlated with OS based on X-title analysis,including DM 10(fatty acyl).DM14(sterol lipids),DM79(steroids hormone),DM82(steroids hormone)DM92(lysophosphatidycholine),DM103(styrenes)and DM125(unknown).DM10.DM14,DM79,DM82.DM92,DM103 and DM 125 are independent factors affecting OS after multi-variables analysis.The predictive model was built based on the β index of the above seven metabolities.The cutoff value of risk score(RS)was as-1.472 after survivalROC analysis,with AUC equal to 0.837.Patients were devided into high risk group(RS>-1.472)and low risk group(RS≤-1.472).The low risk group achieved significantly high OS and PFS than the high risk group(P<0.001,P=0.003).Conclusion:Metabolomic protiling could be applied in early diagnosis and prediction for the efficacy of radiotherapy in NSCLC.The model based on seven metabolites were identified to predict the OS and PFS for patients.The validation group with larger example are needed to confirm the role of the model. |
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