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Journal of Global Oncology Oct 2019The histology of brain tumors determines treatment and predicts outcome. Population-based survival reflects the effectiveness of a health care system in managing cancer....
PURPOSE
The histology of brain tumors determines treatment and predicts outcome. Population-based survival reflects the effectiveness of a health care system in managing cancer. No systematic review of worldwide variation and time trends in survival from brain tumors in children is currently available.
PATIENTS AND METHODS
We considered longitudinal, observational studies comprising children diagnosed with intracranial astrocytic or embryonal tumors. We searched six electronic databases from database inception to September 30, 2018, using complex search strategies. The outcome measure was 5-year survival, estimated through a time-to-event analysis. This study is registered with PROSPERO, number CRD42018111981.
RESULTS
Among 5,244 studies, we identified 47 eligible articles that provided 228 survival estimates. Only five studies were entirely or partially conducted in low-income or middle-income countries. Five-year survival from embryonal tumors increased from 37% in 1980 to approximately 60% in 2009. Although survival for medulloblastoma improved substantially (from 29% to 73% during 1959-2009), survival for primitive neuroectodermal tumors wavered over time (1973-2009) and between countries. Five-year survival from astrocytoma changed very little over the 27 years between 1982 and 2009 (from 78% to 89%). Interpretation of the literature was made difficult by the heterogeneity of study designs.
CONCLUSION
Survival has improved for embryonal tumors, but little change has been observed for astrocytic tumors. We found a striking gap in knowledge about survival from childhood brain tumor subtypes in middle-income and low-income countries, where half of these tumors are diagnosed. Larger studies are needed, including in under-represented countries and based on standardized data collection, to provide up-to-date survival estimates.
Topics: Brain Neoplasms; Cancer Survivors; Child; Databases, Factual; Global Burden of Disease; Humans; Longitudinal Studies; Observational Studies as Topic; Prognosis; Survival Rate
PubMed: 31682549
DOI: 10.1200/JGO.19.00140 -
Acta Neuropathologica Communications Jul 2019Medulloblastoma (MB) is the most common malignant brain tumour in children but also rarely occur in adults. Sonic Hedgehog (SHH) driven MB is associated with aberrant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medulloblastoma (MB) is the most common malignant brain tumour in children but also rarely occur in adults. Sonic Hedgehog (SHH) driven MB is associated with aberrant activation of the SHH signalling pathway. SMO inhibitors, sonidegib and vismodegib, have been used as selective antagonist of the hedgehog pathway that acts by binding to SMO, and inhibits activation of the downstream hedgehog target genes. Several clinical trials investigating SMO inhibitors for the treatment of relapsed MB patients have been published.
METHODS
We conducted a systemic review and meta-analysis among these Phase I and II clinical trials. The pooled effect of SMO inhibitors in relapsed MB were analysed using Reviewer Manager 5.3 software. The clinical efficacy of SMO inhibitors on SHH subtype of MB were measured by the objective response rate. The risk difference was obtained by comparing the ORR between SHH and non-SHH subtypes of MB.
RESULTS
The five studies all had clear criteria for patient recruitment, adequate follow-up time for endpoint assessment and clear definition of tumour responses. MB patients had good compliance in the trials. The pooled objective response rate (ORR) of SMO inhibitor was 37% and 0 against SHH-driven and other MBs. The pooled ORR of sonidegib was 55% among MB and 0 among MB subgroup. Vismodegib also had no efficacy on non-SHH subtype of MB. The sonidegib against SHH-driven MB produced the ORR 1.87-fold higher than that of vismodegib (95%CI 1.23, 6.69). Among paediatric patients, the efficacy of sonidegib was 3.67-fold higher than vismodegib (p < 0.05). A total of 320 cases received SMO inhibitor therapy and 36 cases reported grade 3/4 dose-limiting toxicity (DLT). The rate of grade 3/4 DLT was similar between patients receiving vismodegib and sonidegib (11.6% vs. 11.2%).
CONCLUSION
Sonidegib and vismodegib were well tolerated and demonstrated anti-tumour activity in SHH-driven paediatric and adult MB by effectively inhibiting Hh signalling. These results support the ongoing clinical trials using SMO inhibitors in combination with conventional chemotherapies for the treatment of relapsed MB.
Topics: Anilides; Antineoplastic Agents; Biphenyl Compounds; Cerebellar Neoplasms; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Hedgehog Proteins; Humans; Medulloblastoma; Pyridines; Signal Transduction; Smoothened Receptor; Treatment Outcome
PubMed: 31362788
DOI: 10.1186/s40478-019-0773-8