Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination:A retrospective analysis

BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.

Intrathecal dexamethasone and methotrexate treatment of neoplastic meningitis from solid tumors

Aim:Neoplastic meningitis(NM)from solid tumors is an advanced malignancy with poor prognosis.Intrathecal chemotherapy is a reliable treatment,and we have obtained some experiences in the treatment of NM with intrathecal dexamethasone and methotrexate(IT DXM and MTX).Methods:Retrospective study of 23 patients with NM from lung cancer(n=11),breast cancer(n=3),gastric cancer(n=1),malignant melanoma(n=1),unknown cancer(n=7)was conducted.Among these patients,eight received IT DXM and MTX treatment,and 15 patients were placed into a palliative care group.Overall survival(OS)was compared,and the patients’characteristics,symptoms,and some laboratory examinations were analyzed to find the risk factors affecting OS.Results:OS of IT DXM and MTX group was significantly longer than that of the palliative care group(P=0.01).The median survival(MS)of palliative care group was 7.53 weeks(5.50-9.57;n=15),and of the IT DXM and MTX group,28.63 weeks(12.50-44.75;n=8);IT DXM and MTX prolonged the OS of NM patients(regression coefficient=−2.923),with odds ratio(OR)being 0.054(0.09-0.323).Spinal nerves damage decreased the OS(regression coefficient=1.595),with OR being 4.928(1.382-17.579).Conclusion:IT DXM and MTX have prolonged the patients’MS,which could be used as a fundamental treatment of NM.Time of induction treatment should be flexible and individualized,and induction treatment could restart when central nervous system relapse.Patients with spinal nerves damage are apt to live shorter.