Xenografting for disease modeling of intramedullary spinal cord tumors: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: The overall incidence of intramedullary spinal cord tumors (IMSCT) remains low and clinical trials or standardized treatment strategies are missing. Therefore, multiple animal-based xenograft models (AXM) have been developed to foster preclinical research efforts on IMSCT. We constructed a systematic literature review to summarize and compare all AXM for IMSCT, published until April 16, 2018. METHODS: The review was conducted using 4 independent research databases following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included, if they reported on surgical transplantation of tumor cells or tumor tissue to the spinal cord. Methodological study quality was assessed according to the SYRCLE (systematic review center for laboratory animal experimentation) risk of Bias tool. RESULTS: Systematic search yielded 20 publications dealing with AXM for IMSCT. In summary, 4 tumor entities were analyzed in 23 experiments using ~337 animals, mainly investigating glioblastoma or gliosarcoma biology. Studies varied regarding the use of engrafted animals, surgical techniques and tumor burden. Most commonly authors used heterotopic, transdural injection of immortalized brain tumor cell lines (1 × 105 in 5 µl) into the thoracic spinal cord of immunocompromised rats. Quality assessment demonstrated an unclear risk of bias in most cases. CONCLUSION: Although different AXM for IMSCT have been described so far, one rat model is technically feasible, enables robust experiments and demonstrates reproducible results. However, there is a need for new AXM using orthotopic engraftment of patient-derived tumor cells and for genetically engineered animal models.

Does the expression of glial fibrillary acid protein (GFAP) stain in glioblastoma tissue have a prognostic impact on survival?

OBJECTIVE: Several parameters are known to predict the survival of glioblastoma (GB), including extent of resection and MGMT promotor methylation. Staining for glial fibrillary acidic protein (GFAP) is a common component of routine histological work-up, but its clinical utility in GB is unclear. The aim of the present study was to analyze the predictive value of quantitative GFAP measurements for survival of patients with GB. METHODS: All subjects in our institutional database of patients with primary GB who underwent surgery between 2011 and 2014 with examination of immunohistochemical staining of GFAP were included. Percentage GFAP staining was measured in 5% increments (5-100%). Univariate and multivariate analyses were performed between GFAP values and survival data. Clinically relevant cut-offs for GFAP staining were identified by receiver operating characteristic (ROC) curves. RESULTS: The final cohort consisted of 272GB patients with available quantitative GFAP measurements (mean age, 62 (±11.1) years, 117 females [43%]). Overall survival was 11.4 months (±8.6). Median GFAP value was 70% (range, 5-100%). The ROC curve showed the clinically relevant cut-off for GFAP at 75% (area under the curve: 0.691). Accordingly, GB patients with GFAP≥75% presented poorer survival on Kaplan-Meier survival estimation (P=0.021). Multivariate analysis adjusted for age, extent of resection, preoperative Karnofsky performance status scale, IDH1 mutation and MGMT methylation status confirmed the independent predictive value of GFAP≥75% for overall survival (P=0.032). Finally, patients with GFAP≥75% showed significantly poorer long-term survival than those with GFAP<75%: 5.8% vs. 15.2% (P=0.0183) and 0.8% vs. 8% (P=0.0076) for 2- and 3-year survival, respectively. CONCLUSION: Quantitative immunohistochemical assessment of GFAP staining could provide a novel biomarker for overall and especially long-term survival of patients with GB. Prospective multi-center validation of the prognostic value of GFAP for GB survival is needed.