Prognosis And It Related Factors For Locally Advanced Non-small Cell Lung Cancer After Three-dimensional Conformal Radiotherapy (3D-CRT)

Objective: To evaluate immediate and long-time efficacy, side effect andits related prognostic factors in locally advanced non-small cell lung cancer(NSCLC) after three-dimensional conformal radiotherapy(3D-CRT).Method: From August2000to December2010, a retrospective analysiswas carried out,474patients who suffered from locally advanced NSCLCreceived three-dimensional conformal radiotherapy and eligible for theanalysis. Among them, males in382and female in92cases; median age was63years old; stage IIIA in211and stage IIIB in263.There were165casestreated with radiotherapy alone,175cases with concurrent chemoradiotherapy,and134cases with sequential chemoradiotherapy. There were21cases withhypofractionated3D-CRT, and453cases with conventional fractionatedradiation therapy. There were55cases received conventional radiotherapy(CRT) before later-course3D-CRT, other419cases were treated with3D-CRT(Among them,79cases accepted intensity modulated radiationtherapy).The median equivalent dose was60Gy(44~77Gy).Patients were fixedwith thermoplastic film while quiet respiration and supine position．When theCT scan was performed, the CT images were transferred and restructured inthree dimension by the treatment planning system(TPS)． Then doctordelineated the gross target volume(GTV). GTV included primary tumor andmetastatic lymph node. GTV was enlarged6-8mm in three-dimensionalorientation as the clinical target volume(CTV)．CTV was enlarged5mm inleft, right, anterior and posterior direction, and10mm in superior or inferiordirection as the planning target volume(PTV)．CRT scheme was constituted bytwo-dimensional simulator, and from anterior and posterior direction giventwo fields with SSD100centimeters．The irradiated fields included primary tumor and corresponding mediastinum．The center of irradiated field wasdesigned as the unitary point to calculate dose of tumor, then adding dose by3D-CRT．At last, plan of CRT was matched with late course plan of3D-CRTin TPS. Treatment plan was available in270patients. The related physicalparameters were evaluated by dose-volume histogram(DVH) inTPS．Immediate effect was evaluated by solid tumor’s effect evaluationcriterion of World Health Organization (WHO) after radiotherapy and tocalculation the overall survival rate of1-year,3-years,5-years, the mediansurvival time and the mean survival time. The acute radiation relatedside-effects(such as radiation pneumonitis, irradiation esophagitis and thehematologic toxicity)were evaluated by criterion of RTOG’s acute injurygrade standard．The possible of related prognostic factors on the survival, suchas gender, age, smoking history, histopathology, clinical stage, treatmentmodality, style of radiotherapy, style of fractionation, physical parameterswere evaluated by univariate and multivariate analysis. Statistics analysis wasused with SPSS13.0software, χ2test for analysis of variance for multiplesamples, survival was analyzed by the Kaplan-Meier method, Univariatesurvival analysis was performed with the method of Log-rank test todetermine associations between overall survival rate and related prognosticfactors, and COX proportional hazard model was used for multivariatesurvival analysis. p <0.05was defined as significant difference in statistic.Result: The deadline of the follow-up was30August2013, and thefollow-up rate was96.6%. After radiotherapy, CR in41cases, PR in392cases,SD in31cases, PD in10cases, and the total efficiency rate is91.4％(433/474). By χ2test, stay T was the only factor related with short-time effect,and short-time effect was better in patients with T1-2than T3-4(p <0.05).Forall patients, the median and mean survival time was18months and33.3months, respectively, and1-year,3-years and5-years overall survival was63.0%,24.9%,17.8%, respectively. With univariate analysis, gender, age,histopathology, primary tumor volmle, short-time response, style ofradiotherapy, style of fractionation, chemotherapy, radiation-related pneumonitis, GTV, GTVD100, GTVD95, GTVV60, CTV, CTVD100,CTVD90, CTVV60, CTVV55, PTV were significantly associated with overallsurvival rate（p<0.05）. However, other factors, such as smoking history,tumor location, clinical stage, dose of radiotherapy, irradiation esophagitis, thehematologic toxicity, were not related with overall survival rate（p>0.05）.Withmultivariate analysis, the independent prognostic factors were gender, age,histopathology, short-time response, GTVD100, PTV. There were53.8%(255/474) patients with acute radiation-related pneumonitis after radiotherapy,grade1in62cases, grade2in74cases, grade3in114cases, grade4in5cases, respectively; there were41.1%(195/474) patients with acute radiationesophagitis,95cases in grade1,93cases in grade2,7cases in grade3; therewere23.9%(89/372) patients with leukopenia,60cases in grade1,27casesin grade2,1cases in grade3,1cases in grade4; there were22.0%(82/372)patients with hemoglobin toxicity,69cases in grade1,11cases in grade2,1cases in grade3,1cases in grade4.Conclusions: Curative effect was affirmed and side-effect was toleratedin local advanced NSCLC after3D-CRT. Gender, age, histopathology,short-time response were the independent risk prognostic factors. Patients inmale, of the older ages, with squamous or adenocarcinoma cell carcinoma orwith bad short time response after3D-CRT might have shorter overall survivalrate. There was better prognosis in female, of the younger ages, with otherhistopathologic classifiction or with good short-time response after3D-CRT.3D-CRT combined with chemotherapy might improve survival furtherly,however, hypofractionated radiation therapy or escalated radiation dosecould not potentially improve overall survival. Tumor volume was a reliableindicator of the overall survival of locally advanced NSCLC after3D-CRT,both the total tumor volume(GTV) and the primary tumor volume were thesignificant prognostic factors. Several available target volume parameterscould impact the overall survival.