| Part I:Outcome of concurrent chemoradiotherapy in patients with locally advanced non-small-cell lung cancerPurpose:To analyze the efficacy and toxicity of concurrent chemoradiotherapy(CCRT)for patients with locally advanced non-small-cell lung cancer(NSCLC).Methods:Between Jan 2001 and Dec 2010,251 patients with stage ?(76 ?a and 175?b)NSCLC who received CCRT as initial treatment were reviewed.A median total radiotherapy dose of 60 Gy(range,50-74 Gy)were delivered.174 patients were treated with intensity modulated radiation therapy(IMRT),51 with three dimensional-conformal radiotherapy(3D-CRT)and 26 with 2D-radiotherapy plan.Etoposide/cisplatin(EP)chemotherapy regimen was administered in 112 patients,paclitaxel/carboplatin(PC)regimen in 99 patients,topotecan regimen in 18 patients and other regimens in the remaining 22 patients.The efficacy and toxicity of CCRT were retrospectively analyzed.Results:244 patients were assessable for response,including 6(2.5%)patients with complete resposne(CR),183(75.0%)with partial response(PR),42(17.2%)with stable disease(SD)and 13(5.3%)with progressive disease(PD).At a median follow-up period of 62 months,the 1-,3-,5-year overall survival(OS)and the median OS were 69.2%,31.2%,23.2%and 21 months,respectively.The 1-,3-,5-year progression free survival(PFS)and the median PFS were 40.9%,22.1%,17.7%and 10 months,respectively.Patients with ?a achieved better 5-year OS than that with ?b(29.2%vs.20.7%,x2=2.254,p=0.133).Failure pattern was assessable in 244 patients,including 61(25.0%)local-regional progression alone,55(22.5%)distant metastasis alone and 77(31.6%)with both.The rate of grade ?3 radiation pneumonitis,esophagitis and hematologic toxicity were 4.4%,11.2%and 26.4%,respectively.Conclusions:CCRT provided stage ? NSCLC patients favorable outcome with acceptable toxicities.CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC.Part II:Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapyPurpose:For patients with locally advanced non-small-cell lung cancer(NSCLC),the role of consolidation chemotherapy(CCT)following concurrent chemoradiotherapy(CCRT)is partially defined.The aim of this study was to evaluate the efficacy and toxicity of CCT.Methods:The characteristics of locally advanced NSCLC patients treated with curative CCRT from 2001 to 2010 were retrospectively reviewed.Results:Among 203 patients,113(55.7%)patients received CCT.The median number of delivered CCT was 3 and 89.4%patients completed ?2 cycles.The overall survival(OS)was significantly better for patients in the CCT group compared with that in the non-CCT group(median OS,27 months vs.16 months;5-year OS,30.4%vs.22.5%;p=0.012).The median progression free survival(PFS)were 12 months in the CCT group and 9 months in the non-CCT group(p=0.291).The survival advantages of CCT were significant for males(HR:0.63;95%Cl,0.44-0.90),patients with age<60 years(HR:0.63;95%Cl,0.42-0.95),non-squamous histology(HR:0.44;95%Cl,0.25-0.76),pretreatment KPS?80(HR:0.67;95%CI,0.48-0.93),stage ?b(HR:0.64;95%Cl,0.43-0.95),stable disease(SD)(HR:0.31;95%CI,0.14-0.65)and radiotherapy dose?60 Gy(HR:0.69;95%CI,0.48-1.00).The risk of grade ?3 hematological toxicities was higher in the CCT group than in the non-CCT group,though not significant(45.1%vs.34.4%;p=0.123).Conclusions:CCT might further prolong survival compared with CCRT alone for locally advanced NSCLC without increasing treatment-related toxicities,especially for males,patients with age<60 years,non-squamous histology,pretreatment KPS ?80,stage ?b,SD and radiotherapy dose?60 Gy.Large size prospective investigations that incorporate patient characteristics and treatment response are warranted to validate our findings.Part ?:MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinomaPurpose:Lung adenocarcinoma(LAD)is considered to be a highly aggressive disease with heterogeneous prognosis and the molecular mechanisms underlying tumor progression remain elusive.Growing evidence demonstrates that the dysregulation of microRNAs(miRNAs)plays an important role in various tumor processes.The aim of this study is to discover prognostic miRNA and investigate its role involved in progression of LAD.Methods:Prognosis related miRNA was detected by miRNA microarray using formalin-fixed paraffin-embedded(FFPE)specimens from 87 patients with IIIa-N2 LAD.The cell proliferation was evaluated by Cell Titer 96 AQueous One Solution Cell Proliferation Assay(MTS),and the migration/invasion was evaluated by transwell assay.The bioinformatics methods and luciferase reporter assay were applied to detect the relationship between miRNA and its target.The mRNA and protein levels of miRNA target were determined by quantitative real time polymerase chain reaction(qRT-PCR)analysis,western blot and enzyme-linked immunosorbent assay(ELISA).Changes of angiogenesis induced by miRNA was evaluated by human umbilical vein endothelial cell(HUVEC)tube formation assay.Immunohistochemistry(IHC)analysis was performed in FFPE specimens of patients to evaluate the correlation between miR-29c with microvessel density(MVD)and vascular endothelial growth factor A(VEGFA)expression.Results:miR-29c expression downregulation was significantly associated with unfavorable prognosis in ?a-N2 LAD.miR-29c inhibited cell proliferation,migration and invasion in cell lines.Integrated analysis revealed that VEGFA was a direct target of miR-29c.miR-29c reduced the capability of tumor cells to promote HUVEC tube formation.The compromised cell proliferation,migration/invasion and angiogenesis induced by miR-29c mimic transfection were reversed by transfection of VEGFA expression plasmid.Furthermore,the correlation of miR-29c with MVD and VEGFA was confirmed in patients' samples.Conclusions:miR-29c acts as a tumor suppressor by targeting VEGFA and may represent a promising prognostic biomarker as well as a potential therapeutic target for LAD. |
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