Dosimetric Factors For Risk Of Craniocerebral Toxicity Following IMRT For T4 Nasopharyngeal Carcinoma

ObjectiveThis study aims to identify the dosimetric factors for risk of craniocerebral toxicity after intensity-modulated radiation therapy（IMRT）for T4 nasopharyngeal carcinoma（NPC）.To provide a practical reference for optimizing dose distribution.Materials and methodsFrom 2005 to 2010,patientsstagednon-metastatic T4 NPC treated with IMRT were included in the study.Dose-volume histograms for brainstem,spinal cord,optic nerves（ON）,chiasm（Chi）,temporal lobes（TLs）,age,gender,chemotherapy,cavernous sinus and meningeal invasion were retrospectively analyzed.Survival curves were depicted by using the Kaplan-Meier method,theχ2 test and the Mann-Whitney U test were used for univariate analysis.Multivariable analysis of significant factors was conducted using the Logistic regression.Receiver operating characteristic（ROC）curve and logistic dose-response model were used to determine volume-dose parameters and the radiation dose-tolerance model for predict temporal lobe necrosis（TLN）.ResultsA total of 175 patients were identified.The 5-year OS,PFS,LRFS and DMFS were 63.1%,54.3%,80.1%and 73.9%respectively.No one developed damage to the brainstem,spinal cord,ON or Chi.Overall,97.7%,89.1%and 80.5%patients had exceeded D_max≥54 Gy to stem,Chi,left ON,and right ON,respectively.Besides,87.4%patients had an excess D_max≥45 Gy to cord.A total of 28patientsdeveloped Temporal lobe necrosis（TLN）,which 6 patients developed TLN after the re-course radiotherapy,and 22 patients（13%）developed TLN after the first course.The latency of the primary radiotherapy patients ranges from 17.6-59.3months,with a median of 37.3 months.Only 5 patients（2.9%）had clinical symptom in the.Six patients with TLN after secondary radiotherapy were not included in the temporal lobe dose analysis.Total of 195 temporal lobes were included in the analysis.Maximum dose(D_max)to TLs in the TLN VS.non-TLN patients were 82.4 VS.76.9,p<0.001.The results showed that D_2%was the most statistically significant dose indicator.Cox regression analysis showed that dose to 2%of TLs(D_2%)（Odds ratio[OR]:1.865）,and cavernous sinus invasion（OR:3.107）were predictive for TLN.ROC curve analysis showed that D_2%>74.5 Gy was the tolerated dose cut-off point,and the sensitivity and specificity were 0.93 and 0.56,respectively.ConclusionThe 5-year overall survival rate for T4 patients was 63.1%,with local recurrence and distant metastasis as the main modes of failure.TLN wasone of the major late complication.D_2%of the TLs exceeding 74.5 Gy is associated with high risk of TLN after IMRT of NPC.Overall,97%,87.4%,89.1%,76.0%and 80.0%of the doses of brainstem,optic chiasm,left optic nerve and right optic nerve exceeded the D_maxlimit in RTOG0225 standard,radiation-induced injury wasnot found in this study.The dose constrains of the craniocerebral organs at risk need more flexible definitive criteria.