Clinical Study On Postoperative Radiotherapy Combined With TMZ+MTX Rendezvous Chemotherapy And CSF-ctDNA Monitoring Of Recurrence For Glioblastoma

Objective1.To explore the clinical efficacy and safety of postoperative radiotherapy combined with methotrexate and temozolomide for early treatment of glioblastoma;2.To explore the clinical application value of cerebrospinal fluid circulating tumor DNA(CSF-ctDNA)in early monitoring of tumor recurrence.Methods1.From September 2016 to December 2017,56 patients with glioblastoma admitted to the Department of Neurosurgery,People's Hospital of Zhengzhou University were randomly divided into temozolomide chemotherapy group(control group,26 cases)and temozolomide combined with methotrexate rendezvous chemotherapy group(observation group,30 cases).All patients underwent precise surgical treatment,and tumors were safely removed to the maximum extent.Ommaya reservoir implantation was performed in the observation group.The control group received early temozolomide chemotherapy combined with standard radiotherapy and chemotherapy,while the observation group received interstitial rendezvous chemotherapy of temozolomide and methotrexate on the basis of the control group.The progression-free survival time,overall survival time,adverse drug reactions and the safety of administration methods of the two groups of patients were recorded and analyzed.2.Six patients who completed DNA detection of cerebrospinal fluid circulating tumor within 2 weeks and 6.5 months after operation were selected.Combined with the imaging data of patients,the difference of gene mutation detected twice was analyzed to screen tumor markers for effective monitoring of tumor progression.Results1.The median overall survival time of the rendezvous chemotherapy group was 17.8 months higher than that of the TMZ chemotherapy group 15.1 months(logarithmic rank test,P=0.037);2.The median progression-free survival time in the rendezvous chemotherapy group was 8.4 months higher than 6.8 months in the TMZ chemotherapy group(logarithmic rank test,P=0.034);3.The 12-month and 24-month survival rates of the rendezvous chemotherapy group were 73.3%and 33.3%respectively,which were higher than 61.5%and 23.1%of the TMZ chemotherapy group.4.The most common adverse drug reactions are hematological toxic reactions.Five patients in each group had grade ? or ? blood toxic reactions,which were relieved after symptomatic treatment.There was no significant difference between the two groups(P=0.80).5.In the second CSF-ctDNA test,5 patients with PTEN and TP53 gene mutations were found to have tumor recurrence within 2-4 months after the test in regular imaging examinations.Conclusion1.Methotrexate combined with temozolomide rendezvous chemotherapy can effectively prolong the overall survival and progression-free survival of glioblastoma patients.2.Methotrexate combined with temozolomide rendezvous chemotherapy patients are well tolerated and have no obvious adverse drug reactions.Local administration via Ommaya capsule stroma is safe and effective.3.CSF-ctDNA detection is helpful for dynamic monitoring of tumor marker changes and has certain clinical application value for early monitoring of tumor recurrence.