The Efficacy And Safety Of Intrathecal Chemotherapy Combined With Whole Brain Radiotherapy For Leptomeningeal Metastases From Lung Adenocarcinoma

Purpose:The incidence of leptomeningeal metastasis from lung adenocarcinoma(LM-LUAD)has increased,which seriously affects the survival and quality of life of patients.Intrathecal chemotherapy(ITC)and whole brain radiotherapy(WBRT)have been important methods for the treatment of leptomeningeal metastasis,but there are few studies on their combined treatment.The aim of this study is to evaluate the efficacy and safety of ITC combined with WBRT in the treatment of LM-LUAD,and to analyze the possible prognostic factors.Methods:The clinical data of 63 patients with LM-LUAD admitted to the Department of Radiotherapy,the First Hospital of Jilin University from January 2014 to March 2021 were retrospectively analyzed.All patients received ITC and WBRT.The overall survival(OS),clinical remission rate and adverse reactions of patients after ITC combined with WBRT were analyzed.Results:A total of 63 patients with LM-LUAD were enrolled in this study.The median OS after ITC combined with WBRT was 7.9 months(95% CI 5.122 ～ 10.678).The clinical remission rate was 81.0%(51/63),including 10 cases of complete remission(15.9%),19 cases of obvious remission(30.3%),and 22 cases of partial remission(34.9%).Twelve patients(19%)had no response,including 6 patients(9.5%)with stable disease and 6patients(9.5%)with progressive disease.The main adverse reactions of ITC combined with WBRT were skin injury,alopecia,bone marrow suppression,otitis media,mucosal injury,radiculitis,elevated liver transaminase,and leukoencephalopathy.All patients had different degrees of skin damage and alopecia.In addition,the total incidence of adverse reactions was 44.4%(28/63),and 6 patients(9.5%)had grade 3-4 adverse reactions,including 5 patients(7.9%)with myelosuppression and 1 patient(1.6%)with oral mucositis.In multivariate analysis,age,karnofsky performance status(KPS)score before treatment,clinical remission after treatment,and whether received targeted therapy were independent factors affecting OS.Age < 60 years(HR 2.351,95% CI 1.117 ～ 4.952,P= 0.024),KPS score ≥ 70 before treatment(HR 2.190,95% CI 1.180 ～ 4.067,P = 0.013),remission after treatment(HR 8.658,95% CI 3.001 ～ 24.975,P < 0.01),and received targeted therapy(HR 2.350,95% CI 1.210 ～ 4.565,P = 0.012)had longer OS.Conclusions:1.ITC combined with WBRT can prolong the survival time of LM-LUAD patients and relieve clinical symptoms;2.ITC combined with WBRT has a low incidence of grade 3 and above adverse reactions with acceptable toxicity,which can be relieved after clinical intervention;3.ITC combined with WBRT is an alternative treatment for LM-LUAD.Age,KPS score before treatment,remission after treatment and whether received targeted therapy were independent prognostic factors for OS.