Journal of Neuro-Oncology

The differences in the clinical course and histopathology of sporadic and neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) were investigated retrospectively. The collective comprised 38 NF1 patients and 14 sporadic patients. NF1 patients were significantly younger at diagnosis (p < 0.001) and had a significantly shorter survival time than sporadic patients (median survival 17 months vs. 42 months, Breslow p < 0.05). The time interval to local recurrence and metastatic spread was also significantly shorter in NF1 patients (9.4 months vs. 30.0 months, p < 0.01; 9.1 months vs. 33.2 months, p < 0.001, respectively). In patients with the original histopathological data available (22 NF1 patients, 14 sporadic cases), NF1-associated MPNST showed a significantly higher cellularity compared to sporadic tumors (p < 0.001) whereas sporadic MPNST featured a significantly higher pleomorphism (p< 0.01). Most importantly, while histopathological variables correlated with French Fédération Nationale des Centres de Lutte Contre le Cancer grading in sporadic MPNST, this was not the case for NF1-associated tumors. The differences between NF1-associated and sporadic MPNST in regard to the clinical course and histopathology may reflect some fundamental differences in biology and pathomechanism of the two tumor groups. Our findings indicate the necessity for a separate grading scheme which takes into account the genetic background in NF1 patients.

To report the occurrence of neurolymphomatosis in a patient with previously treated systemic diffuse B-cell lymphoma (DLBCL). A case report. University medical center. A 54-year old woman with previously treated DLBCL developed sequential mono-, di- and triparesis 3-months after completion of systemic therapy. MR of lumbar and brachial plexus revealed diffuse involvement of nerve roots and plexus. High-dose methotrexate and involved-field radiotherapy. Neurolymphomatosis, although rare, is increasingly recognized with peripheral and central nervous system MRI. Treatment remains unsatisfactory as treatment with methotrexate-based chemotherapy and irradiation is only partially effective.

Multidisciplinary studies for glial tumors has produced an enormous amount of information including imaging, histology, and a large cohort of molecular data (i.e. genomics, epigenomics, metabolomics, proteomics, etc.). The big data resources are made possible through open access that offers great potential for new biomarker or therapeutic intervention via deep-learning and/or machine learning for integrated multi-omics analysis. An equally important effort to define the hallmarks of glial tumors will also advance precision neuro-oncology and inform patient-specific therapeutics. This review summarizes past studies regarding tumor classification, hallmarks of cancer, and hypothetical mechanisms. Leveraging on advanced big data approaches and ongoing cross-disciplinary endeavors, this review also discusses how to integrate multiple layers of big data toward the goal of precision medicine. In addition to basic research of cancer biology, the results from integrated multi-omics analysis will highlight biological processes and potential candidates as biomarkers or therapeutic targets. Ultimately, these collective resources built upon an armamentarium of accessible data can re-form clinical and molecular data to stratify patient-tailored therapy. We envision that a comprehensive understanding of the link between molecular signatures, tumor locations, and patients’ history will identify a molecular taxonomy of glial tumors to advance the improvements in early diagnosis, prevention, and treatment.

Objective Facial nerve preservation is a critical measure of clinical outcome after vestibular schwannoma treatment. Gamma Knife radiosurgery has evolved into a practical treatment modality for vestibular schwannoma patients, with several reported series from a variety of centers. In this study, we report the results of an objective analysis of reported facial nerve outcomes after the treatment of vestibular schwannomas with Gamma Knife radiosurgery. Materials and methods A Boolean Pub Med search of the English language literature revealed a total of 23 published studies reporting assessable and quantifiable outcome data regarding facial nerve function in 2,204 patients who were treated with Gamma Knife radiosurgery for vestibular schwannoma. Inclusion criteria for articles were: (1) Facial nerve preservation rates were reported specifically for vestibular schwannoma, (2) Facial nerve functional outcome was reported using the House–Brackmann classification (HBC) for facial nerve function, (3) Tumor size was documented, and (4) Gamma Knife radiosurgery was the only radiosurgical modality used in the report. The data were then aggregated and analyzed based on radiation doses delivered, tumor volume, and patient age. Results An overall facial nerve preservation rate of 96.2% was found after Gamma Knife radiosurgery for vestibular schwannoma in our analysis. Patients receiving less than or equal to 13 Gy of radiation at the marginal dose had a better facial nerve preservation rate than those who received higher doses (≤13 Gy = 98.5% vs. >13 Gy = 94.7%, P < 0.0001). Patients with a tumor volume less than or equal to 1.5 cm3 also had a greater facial nerve preservation rate than patients with tumors greater than 1.5 cm3 (≤1.5 cm3 99.5% vs. >1.5 cm3 95.5%, P < 0.0001). Superior facial nerve preservation was also noted in patients younger than or equal to 60 years of age (96.8 vs. 89.4%, P < 0.0001). The average reported follow up duration in this systematic review was 54.1 ± 31.3 months. Conclusion Our analysis of case series data aggregated from multiple centers suggests that a facial nerve preservation rate of 96.2% can be expected after Gamma knife radiosurgery for vestibular schwannoma. Younger patients with smaller tumors less than 1.5 cm3 and treated with lower doses of radiation less than 13 Gy will likely have better facial nerve preservation rates after Gamma Knife radiosurgery for vestibular schwannoma.

Avoidance of facial nerve palsy is one of the major goals of vestibular schwannoma (VS) microsurgery. In this study, we examined the significance of previously implicated prognostic factors (age, tumor size, the extent of resection and the surgical approach) on post-operative facial nerve function. We selected all VS patients from prospectively collected database (1984–2009) who underwent microsurgical resection as their initial treatment for histopathologically confirmed VS. The effect of variables such as surgical approach, tumor size, patient age and extent of resection on rates facial nerve dysfunction after surgery, were analyzed using multivariate logistic regression. Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3 or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was defined as “facial nerve preservation.” A total of 624 VS patients were included in this study. Multivariate logistic regression analysis found that only pre-operative tumor size significantly predicted poorer facial nerve outcome for patients followed-up for ≥6 and ≥12 months (OR 1.27, 95% CI 1.09–1.49, p < 0.01; OR 1.35, 95% CI 1.10–1.67, P < 0.01, respectively). We found no significant relationship between facial nerve function and age, extent of resection, surgical approach, or tumor size (when extent of resection and surgical approach were included in the regression analysis). Because facial nerve palsy is a debilitating and psychologically devastating condition for the patient, we suggest altering surgical aggressiveness in patients with unfavorable tumor anatomy, particularly in cases with large tumors where overaggressive resection might subject the patient to unwarranted risk. Residual disease can be followed and controlled with radiosurgery if interval growth is noted.

There is little known regarding the immune infiltrate present in pediatric brain tumors and how this compares to what is known about histologically similar adult tumors and its correlation with survival. Here, we provide a descriptive analysis of the immune infiltrate of 22 fresh pediatric brain tumor tissue samples of mixed diagnoses and 40 peripheral blood samples. Samples were analyzed using a flow cytometry panel containing markers for immune cell subtypes, costimulatory markers, inhibitory signals, and markers of activation. This was compared to the standard method of immunohistochemistry (IHC) for immune markers for 89 primary pediatric brain tumors. Both flow cytometry and IHC data did not correlate with the grade of tumor or mutational load and IHC data was not significantly associated with survival for either low grade or high grade gliomas. There is a trend towards a more immunosuppressive phenotype in higher grade tumors with more regulatory T cells present in these tumor types. Both PD1 and PDL1 were present in only a small percentage of the tumor infiltrate. T cell receptor sequencing revealed up to 10% clonality of T cells in tumor infiltrates and no significant difference in clonality between low and high grade gliomas. We have shown the immune infiltrate of pediatric brain tumors does not appear to correlate with grade or survival for a small sample of patients. Further research and larger studies are needed to fully understand the interaction of pediatric brain tumors and the immune system.

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2 P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.

Radiation therapy is often used to treat meningioma with adverse features or when unresectable. Proton therapy has advantages over photon therapy in reducing integral dose to the brain. This study compared the incidence of radiological and clinical adverse events after photon versus proton therapy in the treatment of meningioma. A retrospective review was conducted on patients with meningioma treated with proton or photon therapy at two high-volume tertiary cancer centers. Patients with a history of prior radiation therapy (RT) or less than 3 months of follow-up were excluded. Post-RT imaging changes were categorized into abnormal T2 signal intensities (T2 changes) or abnormal T1 post-contrast and T2 signal intensities (T1c+T2 changes) on magnetic resonance imaging (MRI). Clinical outcomes of adverse events and survival were compared between the proton and photon therapies. Among the total of 77 patients, 38 patients received proton therapy and 39 patients received photon therapy. The median age at diagnosis was 55 years and median follow-up was 2.2 years. No significant differences in symptomatic adverse events were observed between the two groups: grade ≥ 2 adverse events were seen in 4 (10.5%) patients in the proton group and 3 (7.7%) patients in the photon group (p = 0.67). The 2-year cumulative incidences of T2 changes were 38.3% after proton therapy and 47.7% after photon therapy (p = 0.53) and the 2-year cumulative incidences of T1c+T2 changes were 26.8% after proton therapy and 5.3% after photon therapy (p = 0.02). One patient experienced grade ≥ 4 adverse event in each group (p = 0.99). Estimated 2-year progression-free survival was 79.5% (proton therapy 76.0% vs. photon therapy 81.3%, p = 0.66) and 2-year overall survival was 89.7% (proton therapy 86.6% vs. photon therapy 89.3%, p = 0.65). Following RT, high rates of T2 changes were seen in meningioma patients regardless of treatment modality. Proton therapy was associated with significantly higher rates of T1c+T2 changes compared with photon therapy, but severe adverse events were uncommon in both groups and survival outcomes were comparable between the two groups. Future studies will aim at correlating the MRI changes with models that can be incorporated into RT planning to avoid toxicity.