Malignant glioma in Hong Kong Chinese

An analysis of a registry of brain and central nervous system (CNS) tumor patients in Hong Kong comprising of data from both public and private neurosurgical practices (with approximately 98% patients of Chinese origin), suggested geographical or racial variations in disease incidence. The annual incidence of malignant gliomas was 1 case per 100,000 per year for patients of Chinese origin living in Hong Kong; considerably lower than the US incidence of 5.97 cases per 100,000 per year. The most frequently observed glioma subtype was glioblastoma multiforme (GBM, WHO Grade IV), constituting 42% of all glioma cases and 5% of all brain tumor cases in Hong Kong. High--‐‑grade malignant glioma (HGG) was most prevalent in patients aged between 45 and 64 years. 5-ALA-based fluorescence-guided surgery was found to be feasible and safe to adopt in the treatment of 9 local WHO Grade III & IV gliomas patients with positive O’ methylguanine-DNA methyltransferase (MGMT) methylation status. This surgical adjunct helped to achieve a satisfactory extent of removal, and was useful in preserving neurological functions during surgery in eloquent areas when used together with intraoperative functional mapping techniques. Recent advances in glioma molecular biology have played an important role not only in pathological diagnoses and classification, but also in the development of more effective targeted molecular therapies. Bevacizumab has been documented to be well tolerated in Asian patients. It was approved for use as a single-agent in patients with relapsed GBM by the Department of Health of Hong Kong in September 2009. However, known complications such as cerebral hemorrhage and wound dehiscence are of particular concern to neurosurgeons treating patients who have received bevacizumab either before or after surgery. Salvage therapies with either single agent bevacizumab or bevacizumab plus irinotecan appeared to be effective treatment options in Hong Kong patients with recurrent high-grade malignant glioma (HGG), with a good associated 6-month progression-free survival (PFS) rate which was comparable to previously published overseas data in this disease type in the overall population. No difficulty in achieving hemostasis was reported and no cases of post-operative cerebral hemorrhaging occurred; suggesting the potential for more aggressive treatment strategies for HGG.published_or_final_versionSurgeryMasterMaster of Surger

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P &lt; 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.</p

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P &lt; 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.</p

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P &lt; 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses