Low, Justin T

Abstract Purpose: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan. Experimental Design: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy. Results: Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice. Conclusions: This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.

Abstract Background Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a key player in tumor angiogenesis. The drug can halt tumor progression, treat radiation necrosis, and reduce peritumoral edema. Although it does not increase overall survival, bevacizumab can improve progression-free survival and quality of life. In many countries, bevacizumab use in the inpatient setting is restricted due to its significant cost. Here, we explore attitudes towards the use of bevacizumab amidst practitioners treating brain tumors and assess ease of accessing the drug in the inpatient setting. Design/Methods A 10-question survey querying practitioners’ opinions of inpatient bevacizumab utility and its availability was distributed to the membership of the Society of Neuro-Oncology in July 2016. Results Eighty-seven percent felt that there was a role for bevacizumab in the inpatient setting, and 69% reported favorable experiences with bevacizumab use. However, 40% encountered difficulty in obtaining approval for inpatient use. We present two contrasting clinical cases that highlight favorable and unfavorable outcomes when bevacizumab use was and was not permitted, respectively. Conclusions In this sample of neuro-oncology practitioners, there is general consensus that bevacizumab plays an important role in the inpatient treatment of brain tumors. In light of ongoing barriers to inpatient bevacizumab use due to cost concerns, these data motivate the creation of standardized policies for inpatient bevacizumab use that balances its important role in improving quality of life with financial considerations.