A small fraction of tumor stem cells exist in glioma and play a key role in the tumorigenesis and propagation of glioma.They have a close relationship with their niche that offers structural and functional support.In glioma niche,vascular endothelial cells can provide Notch ligands for cancer stem cells to activate Notch signaling pathway and contact with other signaling pathways,maintaining the tumor stem cell self-renewal and increasing resistance of brain tumor stem cells to radiotherapy.Therefore,Notch signaling pathway is considered to be a new therapeutic target of glioma.

Objective:To investigate the safety and efficacy of proton beam radiation therapy (PBRT) in patients with World Health Organization (WHO) GradeⅠ/Ⅱ meningioma.Methods:Twenty-six patients with intracranial ( n=8, 30.8%) or skull-base ( n=18, 69.2%) meningioma treated with PBRT from May 2015 to October 2018 were analyzed retrospectively. The median age of the cohort was 42 years (range 15-79 years). Eight patients had WHO Grade Ⅰ meningioma, and 9 had WHO Grade Ⅱ meningioma, respectively. Nine patients had clinical (radiological) diagnosis without histology. Seven patients received post-surgical PBRT (2 patients underwent Simpson Ⅰ-Ⅲ resection, 5 patients underwent Simpson Ⅳ-Ⅴ resection); 10 patients were irradiated for local recurrence after initial surgical resection. Results:All patients completed planned PBRT without break, and the median dose was 54 Gray-Equivalent (GyE) (range 50.4-60 GyE, 1.8-2 GyE/daily fraction). With a median follow-up of 22.2 (range 1.6-36.4) months, the 2-year overall survival and progression-free survival rates were both 100%. Grade Ⅰ skin erythema and alopecia were observed in 22 patients and Grade Ⅰ mucositis was observed in 2 patients. No acute of late toxicities of Grade 2 or above was observed.Conclusions:PBRT appeared to be a favorable treatment option for intracranial and skull base meningioma. Treatment-induced adverse effects and early response to PBRT were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.