Analysis For Radiation Induced Toxicities In Locally Advanced Non-small Cell Lung Cancer Treated With Intensity Modulated Radiotherapy

PartⅠPredictors and NTCP model for radiation induced lung injury in locally advanced non-small cell lung cancer treated with Intensity Modulated RadiotherapyObjective To investigate the incidence and related predictors for radiation induced lung injury (RILI) in patients with locally advanced non-small cell lung cancer receiving involved-field Intensity Modulated Radiotherapy and build Normal Tissue Complication Probability (NTCP) model.Methods Data were retrospectively collected from inoperable or unresectable 256 patients with stage III NSCLC treated with involved-field IMRT between January 2007 and December 2011. The median total RT dose was 60Gy(50-70Gy) in 30 fractions. Of all patients,109 patients(42.6%) received concurrent chemotherapy. National cancer institute common terminology criteria for adverse events version 3.0 (NCI-CTCAE3.0) was used to evaluate the classification of RILI. Grade≥2 RILI (symptomatic RILI, SRILI) in less than 6 months after radiotherapy served as the end event. Using chi square test and logistic regression model analyzed the related factors of RILI. Using Lyman-Kutcher-Burman(LKB) model to predict SRILI.Results Of all patients, male 215 cases(84%), female 41 cases (16%). The mean age at diagnosis was 59.2 years old.43 cases (16.7%) patients had Grade≥2 RILI. The occurrence of RILI from the beginning of RT was 64 days (20-169 days). Univariate analysis showed that smoking, tumor located in the peripheral or central, double mean lung dose (MLD), double lung V5-V20 were related with the development of SRILI(P=0.108,0.106,0.03,0.049). Multivariate analysis showed the double lung MLD and V5-V20 were significantly related with the development of SRILI (P=0.048). V20 combined with MLD to predict SRILI can make the incidence of SRILI from 21.1% decreased to 5.6%. LKB-NTCP model parameters:TD50=23.57Gy, m=0.47, n=1.42. When NTCP<12.87%, the incidence of SRILI can be controlled at less than 5.6%. The prediction value of LKB-NTCP model for SRILI is larger than that of any single dose parameter.Conclusions Compared with 3DCRT, the incidence rate of SRILI with locally advanced NSCLC treated with involved-field IMRT was acceptable. Double mean lung dose and the volume of lower dose region in DVH of double lung were the significant predictors. The predictive value of LKB-NTCP model for SRILI is better than the single dose parameters, it can be applied to predict the occurrence of SRILI, evaluate the radiotherapy treatment plan and decide the prescription dose.Part ⅡPredictors for radiation induced acute symptomatic esophagitis in locally advanced non-small cell lung cancer treated with Intensity Modulated RadiotherapyObjective To investigate the incidence and related predictors of acute symptomatic esophagitis in patients with locally advanced non-small cell lung cancer (NSCLC) with intensity-modulated radiotherapy (IMRT).Methods Data were retrospectively collected from inoperable or unresectable 256 patients with stage Ⅲ NSCLC treated with involved-field IMRT between January 2007 and December 2011. The median total RT dose was 60Gy(50-70Gy) in 30 fractions. Of all patients,109 patients(42.6%) received concurrent chemotherapy. Grade≥2 AE (symptomatic esophagitis) in during and less than 3 months after radiotherapy served as the end event. National cancer institute common terminology criteria for adverse events version 3.0 (NCI-CTCAE3.0) was used to evaluate the classification of acute esophagitis (AE). The predictive factors for AE were analyzed using logistic regression model.Results 174 patients (68%) had treatment-related Grade≥2 AE:154 cases (60.2%) of grade 2,20 cases (7.8%) of grade 3, the median dose Grade≥2 AE occurred was 30Gy (11-68Gy). For grade≥2 AE, multivariate analysis showed esophageal V5-V60, mean dose and age were independent predictors(P=0.021,0,0.010). For grade>3 AE, multivariate analysis showed esophageal V50-V60, concurrent chemotherapy and BMI were independent predictors(P=0.010,0.003,0.019). Old age to grade≥2 AE and larger BMI to grade≥3 AE were protective factors.Conclusions For patients with locally advanced NSCLC treated with IMRT, esophageal V50-V60 and concurrent chemotherapy were identified as the most accurate predictors of grade≥3AE, and V50 was shown to be the better predictor for grade≥2 and ≥3AE.