Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited.Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions.Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252).
Conclusion:Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.
The purpose of this feasibility study is to develop a fully automated procedure capable of generating treatment plans with multiple fractionation schemes to improve speed, robustness, and standardization of plan quality. A fully automated script was implemented for spinal stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) plan generation using Eclipse v15.6 API. The script interface allows multiple dose/fractionation plan requests, planning target volume (PTV) expansions, as well as information regarding distance/overlap between spinal cord and targets to drive decision‐making. For each requested plan, the script creates the course, plans, field arrangements, and automatically optimizes and calculates dose. The script was retrospectively applied to ten computed tomography (CT) scans of previous cervical, thoracic, and lumbar spine SBRT patients. Three plans were generated for each patient — simultaneous integrated boost (SIB) 1800/1600 cGy to gross tumor volume (GTV)/PTV in one fraction; SIB 2700/2100 cGy to GTV/PTV in three fractions; and 3000 cGy to PTV in five fractions. Plan complexity and deliverability patient‐specific quality assurance (QA) was performed using ArcCHECK with an Exradin A16 chamber inserted. Dose objectives were met for all organs at risk (OARs) for each treatment plan. Median target coverage was GTV V100% = 87.3%, clinical target volume (CTV) V100% = 95.7% and PTV V100% = 88.0% for single fraction plans; GTV V100% = 95.6, CTV V100% = 99.6% and PTV V100% = 97.2% for three fraction plans; and GTV V100% = 99.6%, CTV V100% = 99.1% and PTV V100% = 97.2% for five fraction plans. All plans (n = 30) passed patient‐specific QA (>90%) at 2%/2 mm global gamma. A16 chamber dose measured at isocenter agreed with planned dose within 3% for all cases. Automatic planning for spine SRS/SBRT through scripting increases efficiency, standardizes plan quality and approach, and provides a tool for target coverage comparison of different fractionation schemes without the need for additional resources.
Background
Hyperglycemia has been associated with worse survival in glioblastoma. Attempts to lower glucose yielded mixed responses which could be due to molecularly distinct GBM subclasses.
Methods
Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were subclassified into RTK I (Proneural), RTK II (Classical) and Mesenchymal subtypes using whole genome DNA methylation. Average glucose was calculated by time-weighting glucose measurements between diagnosis and last follow-up.
Results
Patients were stratified into three groups using average glucose: tertile one (<100mg/dL), tertile two (100-115 mg/dL), and tertile three (>115 mg/dL). Comparison across glucose tertiles revealed no differences in performance status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (p=0.9) but decreased with higher glucose (p=0.015). Higher glucose tertiles were associated with poorer OS among RTK I (p=0.08) and mesenchymal tumors (p=0.05), but not RTK II (p=0.99). After controlling for age, KPS, dexamethasone, and MGMT status, glucose remained significantly associated with OS (aHR=5.2, p=0.02). Methylation clustering did not identify unique signatures associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites without differences between molecular subclasses.
Conclusion
Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit to lowering systemic glucose in selected molecular subtypes.
Stereotactic radiation treatment can be used to treat spinal cord neoplasms in patients with either unresectable lesions or residual disease after surgical resection. While treatment guidelines have been suggested for epidural lesions, the utility of stereotactic radiation for intradural and intramedullary malignancies is still debated. Prior reports have suggested that stereotactic radiation approaches can be used for effective tumor control and symptom management. Treatment-related toxicity has been documented in rare subsets of patients, though the incidences of injury are not directly correlated with higher radiation doses. Further studies are needed to assess the factors that influence the risk of radiation-induced myelopathy when treating spinal cord neoplasms with stereotactic radiation, which can include, but may not be limited to, maximum dose, dose-fractionation, irradiated volume, tumor location, histology and treatment history. This review will discuss evidence for current treatment approaches.
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