Clinical Efficacy Of Gamma Knife Radiosurgery In Staged Treatment Of Large Brain Metastases

Objective This study aims to retrospectively analyze and explore the efficacy,safety and prognostic factors of gamma knife radiosurgery in the treatment of patients with large brain metastases,and to provide reference for the selection of clinical treatment options for large brain metastases.Methods From September 2018 to September 2020,the clinical data of 52 patients with large brain metastases treated by Gamma Knife radiosurgery were treated in the Head Gamma Knife Treatment Center of our hospital.A single large brain metastasis with a maximum diameter of<3cm and≤4.5cm among patients with brain metastases was selected for treatment observation and efficacy evaluation.The patient in this study was installed with a stereotactic head frame under local anesthesia,and 3mm thin-layer enhanced MRI was used to scan and locate the brain.The target area was delineated in the GAMMA-TPS planning system,and 40%-50%isodose wire was used to wrap it.For tumor lesions,the median peripheral dose of the first treatment is12 Gy(10-13).The enhanced MRI of the head was perfected 21-30 days after the end of the first-stage treatment,and the appropriate second-stage treatment time was selected according to the degree of changes in the intracranial lesions and the general state of the patient.The second-stage treatment is the same as the first-stage treatment,and the median peripheral dose of the second-stage treatment is 14Gy(12-15).The median interval of the second-stage treatment for all patients was 28 days(25-47 day).All patients received head-enhanced MRI reexamination 2 to 3 months after the end of the second-stage treatment,and compared with the previous imaging data to evaluate the short-term efficacy,and follow-up to observe the long-term efficacy.Local control rate(LCR),objective response rate(ORR),overall survival(OS),progression-free survival(PFS)and various influencing factors The implementation of key analysis,the recent treatment effect selection of the 2009 RECIST 1.1 version of the solid tumor treatment effect evaluation standard,according to the American Association for Radiotherapy oncology,the implementation of the central nervous system(central nervous system,CNS)radiation injury classification standards.The statistical methods are X~2test,paired t test,and one-way analysis of variance.The Kaplan-Meier method was selected for survival analysis,and P<0.05 indicated statistical difference.Results In this study,three-month ORR was 46.2%,one-year LCR was 88.5%,6-month overall survival rate was 74.8%,overall survival rate within 1 year was62.2%,and median OS was 9.16 Months(4.25～18.3 months),PFS is 11.25 months(3.15～15.3months).Before treatment,45 patients had obvious neurological symptoms.After treatment,42 patients(93.3%)had clinical symptoms significantly improved,and 3 patients(6.7%)had stable clinical symptoms and asymptomatic worsening cases.The median KPS score of patients before treatment:70 points(60-70 points),and the median KPS score of patients after treatment is 80 points(80-90 points).In the evaluation of adverse reactions,9 patients(17.3%)had grade 1-2 acute CNS radiotherapy side effects,including headache in 6 cases(11.53%),nausea and vomiting in 3 cases(5.77%),and the obvious symptoms were manifested in the lesion.Patients with large volume load and obvious perifocal edema were all relieved after symptomatic treatments such as mannitol and hormones.One patient(1.92%)developed grade 3-4 acute CNS radiotherapy side effects,seizures,and went through anti-epileptic and epileptic treatments.The edema was relieved after treatment,and no significant neurological-related adverse events were found in other patients.By the end of the follow-up,38 patients died(73.1%),of which 6 died of intracranial lesions,16 cases of primary lesions,9 cases of other metastatic lesions,and 7 cases of systemic failure,accounting for 15.7%of the deaths respectively,42.1%,23.6%and18.4%.Of the 6 patients who died due to intracranial lesions,2 patients died due to the progress of the treatment lesions,and 4 patients experienced new lesions.According to the statistical analysis of local control rate factors,tumor volume,tumor peripheral dose and tumor location are the influencing factors of one-year LCR(P<0.05).Survival univariate statistical analysis showed that uncontrolled primary lesions,total target volume>40cm~3,GPA score≤2 points,RPA grade≥Grade II,KPS score≤70 points,and all are the influencing factors of the patient’s OS.Primary disease control,and whether targeted drugs are used have a significant impact on PFS.Conclusions 1.For large-volume brain metastases that are clinically difficult to treat,you can choose gamma knife staging treatment.The tumor local control rate is higher.The staging time enables the function of the brain tissue after irradiation to be fully restored,and there are few adverse reactions.With high safety,it is one of the effective methods for local treatment of large-scale brain metastases.2.Gamma knife staging treatment reduces the burden of intracranial tumors in the shortest possible time,significantly improves the adverse symptoms of the nervous system,and rapidly improves the patient’s KPS score in the short term,creating time conditions for subsequent systemic treatment.3.Tumor volume,tumor peripheral dose and tumor location are factors that affect the local control rate of patients.Patients with total volume>40cm~3,peripheral dose≤11Gy,and tumor adjacent to functional areas have poor local control.4.Uncontrolled primary lesions,total volume>40cm~3,GPA score≤2 points,RPA grade≥Grade II,KPS score≤70 points,are all influencing factors of the patient’s survival status.