Global consequences of malignant CNS tumours: a call to action
Authors: Lisa M DeAngelis
Journal: The Lancet Neurology (2019)

Tumours of the CNS are among the most feared cancers because they affect the very organ that defines personality and assures physical and cognitive independence. CNS tumours can cause severe disability, including seizures, poor memory or speech problems, and physical dysfunction. These effects can make caring for someone diagnosed with a CNS tumour challenging and often necessitate full-time assistance once the disease has progressed into its later stages.1Schubart JR Kinzie MB Farace E Caring for the brain tumor patient: family caregiver burden and unmet needs.Neuro Oncol. 2008; 10: 61-72Crossref PubMed Scopus (181) Google Scholar CNS tumours can affect the brain or spinal cord and occasionally can disseminate within the CSF. They might occur in individuals at any age and from any background. No environmental exposure, other than previous ionising radiation, or behavioural or lifestyle choices are known to increase the risk of developing these tumours.2Braganza MZ Kitahara CM Berrington de Gonzalez A Inskip PD Johnson KJ Rajaraman P Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review.Neuro Oncol. 2012; 14: 1316-1324Crossref PubMed Scopus (163) Google Scholar Atopic conditions might protect against the development of a malignant brain tumour, but the biological basis for this association in unknown.3Amirian ES Zhou R Wrensch MR et al.Approaching a scientific consensus on the association between allergies and glioma risk: a report from the glioma international case-control study.Cancer Epidemiol Biomarkers Prev. 2016; 25: 282-290Crossref PubMed Scopus (71) Google Scholar In The Lancet Neurology, the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 20164GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; published online Feb 20. http://dx.doi.org/10.1016/S1474-4422(18)30468-X.Google Scholar reports a 4·63 per 100 000 person-years global incidence of malignant CNS tumours, which represents a 17·3% increase from 1990 to 2016. Despite this increase over time, the GBD incidence is lower than the 5·57 per 100 000 person-years incidence reported5Leece R Xu J Ostrom QT Chen Y Kruchko C Barnholtz-Sloan JS Global incidence of malignant and other central nervous system tumors by histology, 2003–2007.Neuro Oncol. 2017; 19: 1553-1564Crossref PubMed Scopus (117) Google Scholar for 2003–07, which uses data from international cancer registries. The difference is likely due to variations in recording information in different cancer registries, but the relative distribution of cases throughout the world was similar to the GBD report. Additionally, the GBD study4GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; published online Feb 20. http://dx.doi.org/10.1016/S1474-4422(18)30468-X.Google Scholar notes an accompanying stable mortality rate, suggesting improvements in treatments over time. The global incidence encompasses wide variation in estimates around the world, possibly attributed to different environmental exposures or variable genetic influences within a population. Incidence is also dependent upon ascertainment, and accurate diagnosis of a CNS tumour requires access to modern neuroimaging and neurosurgery. Thus, it is unsurprising that incidence is lowest in resource-limited environments, such as sub-Saharan Africa and Central America, and the highest incidence is observed in the highest quintile of the Socio-demographic Index (SDI). However, these differences cannot be attributed to health-care access alone, and there might well be important causal indicators within this regional and racial or ethnic variability. For example, the highest incidences are seen in the Nordic countries, with a substantially lower incidence evident in their surrounding countries. In the USA, the incidence of most malignant CNS tumours among the African American population is much lower than in the white population, which reflects what is seen gloablly.6Ostrom QT Gittleman H Truitt G Boscia A Krunchko C Barnholtz-Sloan JS CBTRUS statistical report: primary brain and other nervous system tumors diagnosed in the United States in 2011–2015.Neuro Oncol. 2018; 20: iv1-iv86Crossref PubMed Scopus (1201) Google Scholar Genetic susceptibility loci have been identified for gliomas, but they have been examined only in populations of European ancestry;7Melin BS Barnholtz-Sloan JS Wrensch MR et al.Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.Nat Genet. 2017; 49: 789-794Crossref PubMed Scopus (171) Google Scholar studies of populations from different genetic backgrounds might provide important insights into cause or protection against CNS tumours. The high mortality of CNS tumours is reflected in the much larger rates of years of life lost (YLLs) than of years lived with disability (YLDs); even though disability can be severe from these diseases, early mortality overwhelms the effect of short-term disability. The overall assessment of the effect of these metrics is captured in disability-adjusted life-years (DALYs), which comprises YLLs plus YLDs. The GBD 2016 Brain and Other CNS Cancer Collaborators4GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; published online Feb 20. http://dx.doi.org/10.1016/S1474-4422(18)30468-X.Google Scholar show the effect of SDI on DALYs; increasing SDI until an inflection point around 0·80 is associated with increasing DALYs regardless of incidence. The GBD report4GBD 2016 Brain and Other CNS Cancer Collaborators. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; published online Feb 20. http://dx.doi.org/10.1016/S1474-4422(18)30468-X.Google Scholar provides data on the incidence and consequences of malignant CNS tumours on the world's population. However, low grade and benign tumours can cause severe disability and early death as well. Unlike benign tumours in other areas of the body, benign CNS tumours can cause the same disabling symptoms as seen with malignant tumours. However, their slower growth often means that the patient has these disabilities for many years, if not decades. These tumours often cause early death because they can transform into a malignancy or cause such disability that the patient succumbs to a benign CNS tumour. The GBD report does not clarify which of the malignant tumours included in this study might have started as a lower grade tumour, and it might never capture the transformation if a repeat histology is not obtained. More importantly, it does not measure the considerable burden of these lower grade lesions, which tend to occur in young adults. These patients, even if they remain independent in their own activities of daily living, are often unable to work or be employed in accordance with their level of education, causing substantial financial hardship for a family. Such patients might be erroneously classified as cured according to the definition of 10-year survival of the GBD study even though they usually succumb to their CNS tumour. Those patients who present with a seizure, but are otherwise well, might have a delayed diagnosis in resource-poor regions of the world, leading to underestimation of YLDs. Therefore, the GBD Study gives us the most up-to-date assessment of the minimum burden of malignant CNS tumours over time. Ascertainment bias, poor consensus on histological diagnoses, and access to therapy all affect the incidence and DALYs chronicled here. Furthermore, understanding the effect of lower grade and benign CNS tumours remains a challenge that can no longer be ignored while understanding is sought of the cause of these illnesses and their full effect on the global population. LMD reports personal fees from BTG International, Juno Therapeutics (now Celgene), Sapience Therapeutics, Roche (formerly Genentech), and Tocagen, Inc, outside of the submitted work. Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016CNS cancer is responsible for substantial morbidity and mortality worldwide, and incidence increased between 1990 and 2016. Significant geographical and regional variation in the incidence of CNS cancer might be reflective of differences in diagnoses and reporting practices or unknown environmental and genetic risk factors. Future efforts are needed to analyse CNS cancer burden by subtype. Full-Text PDF Open Access