A Multicenter Prospective Randomized Controlled Phase Ⅱ Clinical Study Of Sequential Or Concurrent Whole Brain Radiotherapy For Limited Number Of Brain Metastases From Non-small Cell Lung Cancer

Objective:To compare and analyze the effect of sequential push and synchronous push on neurocognitive function of whole brain radiotherapy by mini mental state examination(MMSE),and to evaluate the difference between the two methods.Methods:In this study,prospective,multi center,competitive randomized grouping method was used to collect patients with brain metastases from non-small cell lung cancer diagnosed by pathology in Affiliated Hospital of North Sichuan Medical College,Mianyang Central Hospital,Guangyuan Central Hospital,Suining Central Hospital,Dazhou Central Hospital and Nanchong Central Hospital from October 2017 to December 2020 Imaging examination confirmed that the number of lesions was 1-10.The patients who met the inclusion criteria were randomly divided into whole brain radiotherapy sequential boost group(group A:WBRT+SEB)and whole brain radiotherapy Synchronous Boost group(group B:WBRT+SIB):group A,30 cases,whole brain irradiation 30Gy/10fx,after irradiation,relocation and delineation of metastatic target area,boost irradiation:12Gy/3fx;group B,39 cases,whole brain irradiation 30Gy/10fx,concurrent brain metastasis irradiation:40Gy/10fx.All patients were assessed with MMSE score before treatment,at the end of treatment,1 month,3 months and 6 months after treatment,and the differences of neurocognitive function between the two radiotherapy methods were analyzed.All patients were examined with enhanced MRI at 1 and 6 months after radiotherapy to evaluate the efficacy of intracranial lesions.The objective remission rate(ORR),local control rate(DCR)and PFS rate of intracranial lesions at 6 months were compared between the two groups.Results:1.A total of 72 cases were included in this study,3 cases in group a withdrew from the study,and 69 cases were effective.There was no significant difference in the general clinical baseline characteristics between the two groups(P>0.05);2.The MMSE score of group A at the end of radiotherapy was 24.33±2.99,which had no significant difference compared with the MMSE score of 24.33±2.96 before radiotherapy(P>0.05);the MMSE scores of group A at 1,3 and 6 months after radiotherapy were 23.21±3.1,22.65±3.77 and 22.41±3.43 respectively,which showed a progressive downward trend compared with the MMSE score of 24.33±2.96 before radiotherapy(P<0.05).The MMSE score of group B at the end of radiotherapy was 23.67±3.73,which had no significant difference compared with that before radiotherapy(23.74±3.67,P>0.05);the MMSE scores of group B at 1,3 and 6 months after radiotherapy were 22.38±4.62,21.28±4.35 and 21.19±4.13,which showed a progressive downward trend compared with that before radiotherapy(23.74±3.67,P<0.05).3.The MMSE scores of group A were 23.21±3.1 and 22.65±3.77 at 1 and 3 months after radiotherapy,respectively,with statistical significance(P<0.05);the MMSE scores of group A were 22.65±3.77 and 22.41±3.43 at 3 and 6 months after radiotherapy,respectively,with no statistical significance(P>0.05).The MMSE scores of group B were 22.38±4.62 and 21.28±4.35 at 1 and 3 months after radiotherapy,respectively,with statistical significance(P<0.05);the MMSE scores of group B were 21.28±4.35 and 21.19±4.13 at 3 and 6 months after radiotherapy,respectively,with no statistical significance(P>0.05).4.There was no significant difference in MMSE scores between group A and group B before radiotherapy,at the end of radiotherapy,1,3 and 6 months after radiotherapy(P>0.05).5.The MMSE scores of group A were 25.270±2.219,25.400±2.414,24.00±2.449,23.170±3.186 before radiotherapy,at the end of radiotherapy,1 month and 6 months after radiotherapy,respectively.The MMSE scores of group B were 23.530±3.674,23.470±3.730,22.250±4.703,20.810±3.945,and there was no significant difference between the two groups(P>0.05).A.The MMSE scores of group B were 23.710±2.998 and 20.890±4.263 at 3 months after radiotherapy,and the difference was statistically significant(P<0.05).6.One month after radiotherapy,the effect of enhanced MRI was evaluated.In group A,CR:2 cases,PR:19 cases,SD:3 cases,PD:1 case,DCR was 96.00%,ORR was 84.00%;in group B,CR:1 case,PR:27 cases,SD:5 cases,PD:2 cases,DCR was 94.30%,ORR was 80.00%;there was no significant difference in DCR and ORR between the two groups(P>0.05).7.Six months after radiotherapy,the effect of enhanced MRI was evaluated.The 6-month intracranial PFS rates of group A and group B were 50.0%and 58.0%,respectively.There was no significant difference in the 6-month intracranial PFS rate between the two groups(P>0.05).Conclusion:1.Neurocognitive impairment occurred in both groups at each stage after radiotherapy,and reached the peak at 3 months after radiotherapy;2.The neurocognitive impairment of whole brain radiotherapy combined with sequential bolus was milder than that of synchronous bolus in the subgroups with the number of lesions≤3;3.There was no significant difference in local control rate,objective remission rate and 6-month intracranial PFS rate between the two groups.