Lai‐Fung Li

// Peter Y.M. Woo 1 , Tai-Chung Lam 2 , Jenny K.S. Pu 3 , Lai-Fung Li 3 , Roland C.Y. Leung 4 , Jason M.K. Ho 1 , James T.F. Zhung 5 , Belinda Wong 6 , Timonthy S.K. Chan 7 , Herbert H.F. Loong 8 and Ho-Keung Ng 9 1 Department of Neurosurgery, Kwong Wah Hospital, Hong Kong 2 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 3 Department of Neurosurgery, Queen Mary Hospital, Hong Kong 4 Department of Medicine, Queen Mary Hospital, Hong Kong 5 Department of Neurosurgery, Kwong Wah Hospital, Hong Kong 6 Pharmacy and Medical Therapeutics, Kwong Wah Hospital, Hong Kong 7 Department of Pathology, Kwong Wah Hospital, Hong Kong 8 Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong 9 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Correspondence to: Tai-Chung Lam, email: lamtc03@hku.hk Keywords: glioblastoma; BRAF V600E mutation; targeted therapies; BRAF-MEK inhibitors Received: August 20, 2018     Accepted: April 03, 2019     Published: June 04, 2019 ABSTRACT Background Up to 15% of young adults with glioblastoma have the activating oncogenic BRAF V600E mutation, an actionable target of the MAPK signal transduction pathway governing tumor cell proliferation. Small molecule inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to confer a survival advantage for patients with BRAF V600E mutant advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAF V600E mutant glioblastoma (GBM) as primary treatment due to extenuating clinical circumstances that prohibited the prescription of standard treatment. Case Presentation The two patients were both 22 years old on presentation. After the initial tumor resection, they both developed rapid deterioration in performance status within a few weeks due to leptomeningeal metastases. In view of the critical condition, BRAF and MEK inhibitors were prescribed as first line treatment. The two patients both achieved dramatic clinical response, which was parallel to the impressive radiological regression of the disease. Unfortunately, the duration of disease control was short as drug resistance developed rapidly. The two patients died 7 and 7.5 month after initial diagnosis of GBM. Conclusions Primary treatment with inhibitors of BRAF and MEK can lead to tumor regression for patients with BRAF V600E mutant glioblastoma. We therefore recommend that all young GBM patients should undergo BRAF V600E mutation testing, especially for those with unusual aggressive clinical course.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( β =5.041, 3.324-6.758 and β =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( β =3.596, 0.353-6.839; P =0.031 and β =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( β =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.