Investigate The Effect Of Combined Therapy And Study Of Tumor Marker Associated With Small-cell Lung Cancer

Small cell lung cancer (SCLC) is one special kind of undifferentiatedcarcinoma of the lung. It is characterized by more malignance, specificbiologic behavior and poor prognosis. The cancer cell originate fromKulchitsky cell of the lung, and belongs to neuroendocrine tumor. Afterdiagnosis, the median survival time is less than3months and the2-yearsurvival rate is not more than1%if there is no treatment policy. BecauseSCLC can relapse rapidly and metastasize widely at early stage,approximately30to40percent of it is limited-stage (LS) at clinical diagnosis.SCLC is sensitive to chemotherapy and radiotherapy, so it is necessary toadopt combined therapy. It is not clear that which modality of combinedtherapy could be chosen to improve the prognosis for LS-SCLC and it becomethe hot issue for oncologist. Consequently, the purpose of this study is toinvestigate the outcome of patients with LS-SCLC after combined therapy andto evaluate the prognostic factors.SCLC belongs to neuroendocrine tumor and has specific biologic behavior,which is probably relevant to some tumor marker. Recently, gastrin-releasingpeptide (GRP) and its receptor (GRPR) are tumor marker studied frequentlyand express highly in SCLC. The combination of GRP and GRPR canaccelarate the growth and metastasis of SCLC. So the purpose of the study isto investigate the relationship between tumor marker and local control,prognosis and metastasis of patients with SCLC and to evaluate the value oftumor marker forecasting the metastasis.Part1:A prognostic analysis for patients with limited-stage small-celllung cancer treated by combined therapyObjective: The aim of this study was to analyze the outcome of patients with limited-stage small-cell lung cancer (LS-SCLC) treated by combinedtherapy and to evaluate the prognostic factors.Methods: Data from158patients with SCLC after combined therapybetween January2006and June2008were retrospectively analyzed. Allpatients had histological or cytological confirmation of SCLC, and wereclassified as limited-stage disease. There were120(75.9%) male and38(24.1%) female. The median age was55years old (range,24⁷8years). Themedian volume of primary tumor before therapy were95.0cubic centimetre(range,3.2³600.0cubic centimetre). One hundred and forty-six patientsreceived chemotherapy, and the median chemotherapy cycle was5(range,1¹7cycles). One hundred and twenty patients received radiotherapy, and themedian radiotherapy dose was54Gy (range,30.0⁷0.0Gy). Forty-ninepatients received surgery. The combined therapy included radiotherapy＋/－chemotherapy, surgery＋/－chemotherapy and surgery＋radiotherapy＋/－chemotherapy. The method of Kaplan-Meier was used for survival ratesanalysis.Results: The overall response rate (CR+PR) was86.7%. The mediansurvival time (MST) was24months, and the1-,2-and3-year survival rateswere76.3%,48.9%and39.1%, respectively. The1-,2-and3-year survivalrates of patients receiving radiotherapy＋/－chemotherapy, surgery＋/－chemotherapy and surgery＋radiotherapy＋/－chemotherapy were73.0%,41.4%,30.3%and79.0%,60.5%,54.4%and90.9%,81.8%,71.6%,respectively. The difference was not statistically significant in the analysisafter stratification by clinical stage. In univariate analyses, the clinical stage,short-term clinical effect, chemotherapy, radiotherapy, radiotherapy dose andsurgery were significantly associated with prognosis. The multivariate analysisshowed that short-term clinical effect, chemotherapy, and radiotherapy dosewere independent factors influencing prognosis.Conclusion: The combined therapy of radiotherapy, surgery andchemotherapy may obtain good outcome without significant difference forpatients with LS-SCLC. We need a further study to choose the best modality of combined therapy.Part2:A study of patients with limited-stage small-cell lung cancer afterthoracic radiotherapy combined with systemic chemotherapyObjective: The aim of this study was to evaluate the effect of patients withlimited-stage small-cell lung cancer (LS-SCLC) treated by thoracicradiotherapy combined with systemic chemotherapy.Methods: Data from107patients with SCLC after radiotherapy combinedwith chemotherapy between January2006and June2008were retrospectivelyanalyzed. All patients had histological or cytological confirmation of SCLC,and were classified as limited-stage disease. There were82(76.6%) male and25(23.4%) female. The median age was54years old (range,24⁷3years).The median volume of primary tumor before therapy were135.0cubiccentimetre (range,3.2⁴89.0cubic centimetre). All patients receivedradiotherapy. There were82patients (76.6%) received radiotherapy ofinvolved field, and the median radiotherapy dose was56.0Gy (range,36.0⁶6.0Gy). In another25patients (23.4%), the involved field receivedradiotherapy of median dose56.0Gy (range,50.0⁷0.0Gy), and the lymphaticdrainage area of ipsilateral hilum and mediastinum received prophylacticradiotherapy of median dose40.0Gy (range,30.0⁵2.0Gy). Ninety-ninepatients received chemotherapy, and the median chemotherapy cycle was5(range,1¹0cycles). There were25patients receiving radiotherapysequentially to chemotherapy,25receiving radiotherapy consolidated withchemotherapy, and49receiving radiotherapy concurrently with chemotherapy.The method of Kaplan-Meier was used for local control rates, survival rates,and metastasis rates analysis.Results:(1) The overall response rate (CR+PR) was87.9%. The1-,2-and3-year local control rates were83.1%,70.0%and64.0%, respectively. Inunivariate analyses, short-term clinical effect and chemotherapy weresignificantly associated with local control. But in multivariate analysis, thevolume of primary tumor, T stage, short-term clinical effect, radiotherapy dose,GTVD_mean, and PTVCI were independent factors for the local control.(2) The median survival time (MST) was19months and the1-,2-and3-year survivalrates were73.8%,38.8%and27.6%, respectively. In univariate analyses, thevolume of primary tumor, chemotherapy, and PTVD₉₅were significantlyassociated with prognosis. The multivariate analysis showed that pleuraleffusion,the volume of primary tumor, T stage, chemotherapy, target range ofradiotherapy, radiotherapy dose, GTVHI, PTVD_mean, and PTVD₉₅wereindependent factors influencing the prognosis.(3) The1-,2-and3-yearmetastasis rates were44.2%,67.4%and70.3%, respectively. In univariateanalyses, the volume of primary tumor, T stage, short-term clinical effect,local control, chemotherapy and target range of radiotherapy weresignificantly associated with metastasis. But in multivariate analysis, age, thevolume of primary tumor, T stage, target range of radiotherapy, and PTVCIwere independent factors influencing metastasis.Conclusion: In LS-SCLC, the modality of radiotherapy combined withsystemic chemotherapy does not affect the local control, prognosis, andmetastasis. The volume of primary tumor and T stage is significantlyassociated with not only local control, but also prognosis and metastasis ofpatients with LS-SCLC.Part3:A study of tumor marker associated with small-cell lung cancerObjective: The aim of this study was to investigate the relationshipbetween tumor marker and local control, prognosis and metastasis of patientswith small-cell lung cancer and to evaluate the value of tumor markerforecasting the metastasis.Methods: Data from73patients with SCLC between January2006andJune2008were retrospectively analyzed. All patients had histologicalconfirmation of SCLC. There were54(74.0%) male and19(26.0%) female.The median age was53years old (range,27⁷3years). The median volume ofprimary tumor before therapy were100.0cubic centimetre (range,6.0⁴89.0cubic centimetre). Thirty-eight (52.1%) patients received surgery, and35(47.9%) patients received radiotherapy. All patients' paraffin-embedded tumortissues were obtained from the Pathology Department, and were cut in4-μm sections. The expression of NSE, GRP, and GRPR were checked byimmunohistochemistry. The method of Kaplan-Meier was used for survivalrates and metastasis rates analysis. The Log-rank test was used for correlationbetween antibody expression and prognosis and metastasis.Results: NSE, GRP, and GRPR were detected in71.2%,79.5%, and75.3%,respectively, of all tumor specimens. The expression of GRP was correlated tothat of GRPR significantly (P=0.000). The expression of GRP and GRPRwere associated with patients' prognosis and metastasis significantly (P＜0.05). The sensitivity of the expression of GRP and GRPR forecasting themetastasis were both71.4%, and the specificity of them were83.9%and90.3,respectively.Conclusion: GRP and GRPR may play an important role in the small-celllung cancer process, and may be an important tumor marker forecasting theinvasion and metastasis of SCLC. The study may provide a molecular basisfor exploiting target of immunotherapeutic purposes in SCLC.