Pretreatment inflammatory indices predict Bevacizumab response in recurrent Glioma

Aim:It remains unclear what the best therapeutic option for recurrent glioma patients after Stupp treatment is.Bevacizumab(BVZ)is commonly administered in progression,but it appears that only some patients benefit.It would be useful to find biomarkers that determine beforehand who these patients are.Methods:The protocol included 31 high-risk progressing glioma patients after Stupp treatment who received BVZ 5-10 mg/kg every 14 days and temozolomide(3-19 cycles,150-200 mg five days each 28-day cycle)during a mean of eight cycles of BVZ or until tumor progression or unacceptable toxicity.We analyzed the clinical outcome values of inflammatory indices measured before BVZ administration.Results:Lymphocyte level before BVZ administration was the best independent predictor of overall survival(HR=0.34;95%CI:0.145-0.81;P=0.015).The area under the receiver operating characteristic(ROC)curve was 0.823,with 1.645 being the optimal cut-off value,and 0.80 and 0.85 the sensitivity and specificity values,respectively.Responder and non-responder survival curves were also significantly different,considering the first and second tertiles as cut-off points.The number of BVZ cycles was not related to lymphopenia.Pretreatment neutrophil platelet levels,platelet-to-lymphocyte ratio(PLR),and neutrophil-to-lymphocyte ratio(NLR)did not have independent predictive value.Inflammatory variables were not correlated with each other.However,patients with high NLR and PLR simultaneously(double positive PLR-NLR)showed a worse clinical outcome than the rest(P=0.043).Conclusion:Pretreatment lymphocyte levels and double positive PLR-NLR could be used as non-invasive hematological prognostic markers for recurrent gliomas treated with bevacizumab.A close relationship emerged between inflammation and angiogenesis.

Bevacizumab rescue therapy extends the survival in patients with recurrent malignant glioma

Objective： We retrospectively studied the efficacy of bevacizumab as salvage therapy for recurrent malignant glioma with a focus on the overall survival （OS）. Methods： Patients who received a therapy other than surgery for recurrent malignant glioma were included. Efficacy was evaluated using MRI. Neurological function was evaluated using the Response Assessment in Neuro-Oncology （RANO）. The survival rate was calculated using the Kaplan-Meier method. Results： Fifty-one patients with recurrent glioma （31 grade Ⅲ, 20 grade Ⅳ） were included. Among them, 22 subjects （43.1%） received bevacizumab. The median OS was 10.2 months （range, 1 to 27 months）. Patients receiving bevacizumab had comparable OS （a median of 9.9 vs. 10.0 months） and similar 6-month survival rate （43% vs. 34%） to those who did not receive bevacizumab. A subgroup analysis failed to notice any significant difference in grade Ⅲ glioma patients receiving bevacizumab vs. those who did not. The median survival was significantly longer at 8.9 months （range, 4 to 13 months） in grade Ⅳ glioma patients receiving bevacizumab than in those who did not （5.6 months, range, 2 to 7 months, P=0.042）. The 6-month survival rate was higher （83 %） in those who received bevacizumab than in those who did not （47 %, P=0.046）. No grade 3/4 adverse events were observed in any patient. Conclusions： Bevacizumab, as a rescue therapy, provides a survival benefit for recurrent grade IV glioma.

Re-irradiation for high-grade gliomas:Has anything changed?

Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,published experience,and a better radiobiological knowledge of brain tissue have positioned re-irradiation(re-RT)as an option for many of these patients.Decisions must be individualized,taking into account the pattern of relapse,previous treatment,and functional status,as well as the patient’s preferences and expected quality of life.Many questions remain unanswered with respect to re-RT:Who is the most appropriate candidate,which dose and fractionation are most effective,how to define the target volume,which imaging technique is best for planning,and what is the optimal timing?This review will focus on describing the most relevant studies that include re-RT as salvage therapy,with the aim of simplifying decision-making and designing the best available therapeutic strategy.

Photodynamic Therapy Mediated by 5-Aminolevulinic Acid Suppresses Gliomas Growth by Decreasing the Microvessels

Although 5-aminolevulinic acid（5-ALA）-mediated photodynamic therapy（PDT） has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups： receiving 5-ALA-PDT（group A）, laser irradiation（group B）, and mock procedures but without any treatment（group C）, respectively. The growth, histology, microvessel density（MVD）, and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced（P〈0.05）, MVD was significantly decreased（P〈0.001）, and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

Subject Code:H30With the support by the National Natural Science Foundation of China,the research group led by Prof.Zhang Can(张灿)from China Pharmaceutical University made important progress in the chemotherapy of post-operative malignant glioma,which was published in Nature Nanotechnology(2017,12(7):692—700).