Brainstem Dose Restriction Could Be Over 54Gy-brainstem Dose And Three-year Followup Analysis On 105 Nasopharyngeal Cancer Patients With Clivus Involvement Treated With Intensity Modulated Radiation Therapy

Object: Clivus is the closest bone structure to brainstem.It is also the common site of skull base involvement of the locally advanced nasopharyngeal carcinoma.In patients receiving definitive radiotherapy,clivus involvement may result in a greater dose of brainstem than the maximum dose 54 Gy limit recommended by 2010 Experts Consensus on Nasopharyngeal Cancer Treatment.The current study retrospectively analyzed the dose of brainstem and three-year follow-up results of locally advanced nasopharyngeal carcinoma patients with clivus involvement in Sichuan Cancer Hospital.We also tried to find out tumor and clivus-associated factors that might have impact on brainstem dose,which could be helpful for decision-making when similar patients were encountered.Methods : From January 2011 to December 2012,a total of 105 nasopharyngeal cancer patients with clivus involvement received definitive chemoradiotherapy in Sichuan Cancer hospital.Among them,37 cases were T3,68 cases were T4,according to the seventh edition of UICC/AJCC staging system.The ages are 21-72 years(median,47 years).The brainstem dose was summarized for all patients.Seventy-seven patients had their planningscomputed on Eclipse system,on which new structure adding is permissible.The entire clivus and the involved clivus were contoured for these patients.The volume of involved clivus,the shortest distance between clivus/involved clivus and brainstem were measured.Kaplan-Meier method was used to generate the survival curve.Life table method was used to calculate the survival rate.The log-rank method was used to perform univariate analysis on prognostic factors.The COX risk ratio model was used to perform multivariate analysis.To analyze the factors which have impact on brain stem dose,Chi square test and logistic risk regression model were used for univariate and multivariate analysis,respectively.P<0.05 was recognized as statistically significant.Results: The median follow-up time was 44 months,during the follow-up period,eight cases suffered local recurrence,14 cases developed distant metastasis.There were 16 patients died.Among them,three died of recurrence,four died of metastasis,one died of other malignancy,two died of tumor related complications,six died of unknown causes.The three-year overall survival rate,local recurrence free survival rate,distant metastasis free survival rate,and progression free survival rate were 88.6%;94.9%;86.3%;77%,respectively.The cumulative dose of irradiation of the clivus(D95)were from 20.56 Gy to72.23Gy(median,60.32Gy);involved clivus volume were from 0.5cm3 to18.6cm3(median,4.2cm3),the cumulative dose of the involved clivus(D95)were from 61.67 Gy to 81.68Gy(median,72.77Gy),the maximum dose(Dmax)of real brainstem were from 44.29 Gy to 72.05Gy(median,56.4Gy),72/105(46/77)cases were greater than 54 Gy,26/105(11/77)cases were greater than60Gy;2/77 cases of real brainstem D01(dose of 1% volume)were greater than60 Gy,72/77 cases of the real brainstem received D1cc(dose of 1cc volume)were less than 54Gy;When adding 1mm margin to brainstem(brainstem plus 1mm),D1 cc were from 37.86 Gy to 65.68Gy(median,51.59Gy),3/77 cases were greater than 60 Gy,9/77 cases of brainstem D01 were greater than 60Gy;When adding 2mm margin to brainstem(brainstem plus 2mm),D1 cc were from41.10 Gy to 68.40Gy(median,54.63Gy),12/77 cases were greater than 60 Gy,1/77 cases was greater than 66 Gy,22/77 cases of brainstem D01 were greater than 60 Gy.Because brainstem restriction is not strictly set at Dmax 54 Gy,70/77 cases of involved clivus D95(dose of 95% volume)were greater than66 Gy,whereas all 77 cases have their D90(dose of 90% volume)greater than66 Gy.In the prognostic factor analysis,dose of involved clivus and dose of brainstem had no impact on survival.In the analysis of factors that correlated with high brainstem dose,it is proved that whole part of clivus involvement and higher dose of involved clivus were associated with higher brainstem dose.Conclusion: The results of current study showed that when Dmax of real brainstem were set over 60 Gy and D1 cc not more than 54 Gy,it is safe to deliver over 66 Gy to primary tumor and involved clivus.The local control rate of the current cohort of patients was close to 95%,which was quite satisfied.