Incidence of glioblastoma
Gliomas are the most common type of malignant brain tumor in adults. Of the gliomas, glioblastoma (astrocytoma grade IV) is the most common, and represents approximately 27% of all primary brain tumors, and 80% of malignant primary brain tumors in the United States. Incidence of glioblastoma in the United States varies significantly by sex, race, ethnicity, and age ( Fig. 2.1 ). From 2006 to 2012, glioblastoma occurred at an overall average annual age-adjusted incidence rate (AAAIR) of 3.20 (95% confidence interval [95% CI], 3.17–3.22) per 100,000 population. Glioblastoma is 1.6 times more common in men than in women, with an AAAIR of 3.99 (95% CI, 3.94–4.03) per 100,000 in men, and 2.53 (95% CI, 2.50–2.56) per 100,000 in women. Incidence of glioblastoma is significantly higher in non-Hispanic people (AAAIR, 3.28, 95% CI, 3.25–3.31) compared with Hispanic people (AAAIR, 2.41; 95% CI, 2.33–2.50). Glioblastoma is most common in white people (AAAIR, 3.45; 95% CI, 3.42–3.48), compared with black people (AAAIR, 1.76; 95% CI, 1.69–1.82), American Indian/Alaska natives (AIAN) (AAAIR, 1.47; 95% CI, 1.25–1.70), and Asian/Pacific Islanders (API) (AAAIR, 1.60; 95% CI, 1.51–1.70). Incidence of glioblastoma increases with increasing age. Incidence is lowest among people 0 to 19 years old (AAAIR, 0.15; 95% CI, 0.13–0.16) and highest among those 75 years and older (AAAIR, 13.66; 95% CI, 13.42–13.91).
Incidence time trends
There was no significant increase in incidence of glioblastoma in the United States between 2000 and 2010. This trend is similar to patterns of incidence in other countries, including Australia and the United Kingdom. Previous analyses showed an increasing incidence of malignant brain tumors during the 1980s and the 1990s, but this is thought to be the result of screening bias caused by increasing access to and use of medical imaging technologies such as computed tomography (CT) and MRI.
Survival after diagnosis with glioblastoma
Glioblastoma has one of the poorest survival rates of any malignant brain tumor, and contributes disproportionately to cancer mortality and morbidity. Median survival after diagnosis with glioblastoma is approximately 12 months, and this survival period increases to approximately 14 months when patients are treated with current standard therapy, which consists of maximal safe surgical resection followed by concurrent radiation and temozolomide. Between 2000 and 2012 in the United States, glioblastoma had a 1-year relative survival rate of 37.8% (95% CI, 37.3%–38.4%), with 5.1% (95% CI, 4.8%–5.7%) of persons surviving 5 years after diagnosis ( Fig. 2.2 ). One-year survival rates have improved since 2000, likely because of the current standard therapy being widely adopted. Survival rates over time vary significantly by age at diagnosis, with persons aged 20 to 34 years having the best overall survival. There are some small differences in 1-year survival by sex and ethnicity, but there are no significant differences by sex, ethnicity, and race in long-term survival with glioblastoma.
Survival time trends
There have been significant increases in both 1-year and 5-year survival after diagnosis with glioblastoma since 1973 ( Fig. 2.3 ). From 1997 to 2012, 1-year survival increased with an annual percentage change (APC) of 3.7% (95% CI, 3.1%–4.3%) from 24.3% (95% CI, 21.4%–27.2%) at the beginning of the time period, to 43.0% (95% CI, 37.6%–48.3%) at the end of the time period. Five-year survival also increased from 1997 to 2012, with an APC of 8.0% (95% CI, 5.1%–11.0%) from 2.1% (95% 1.3%–3.3%) at the beginning of the time period to 5.6% (95% CI, 4.7%–6.7%) at the end of the time period. This trend may be caused by a wide variety of factors including increased screening and earlier detection caused by improvements in medical imaging technologies, as well as the introduction of new treatment modalities, such as the current standard therapy in the early to mid-2000s.
Long-term survival in glioblastoma
The National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) has been collecting data on cancer diagnoses in population-based registries since 1973. This program initially started with 9 registries, but has since increased to 18 (comprising ∼26% of the United States population). From 1973 to 2012, there were 51,152 persons diagnosed with a glioblastoma in the SEER data set; 1611 of these persons (3.1%) survived at least 5 years after diagnosis, and approximately 733 (54% of 1611) were still alive as of 2012. Compared with the population of persons who lived 18 months or less after their diagnoses, this population is significantly younger, with mean age at diagnosis of 48.3 years compared with 63.4 years ( P <.001). Slightly more long-term (> 5 years) and median-term (< 18 months) survivors were male, with no significant differences in gender distribution between the two groups. In addition, fewer in this population were white (88.4% compared with 91.4%; P <.001), with 5.9% and 4.9% of these long-term survivors being black and API, respectively. A larger proportion of these long-term survivors are Hispanic compared with those who lived 18 months or less (10.6% compared with 7.2%; P <.001).
Risk factors for glioma
Environmental Risk Factors
Many environmental and behavioral risk factors have been investigated as causative for glioma. The only well-validated factors are an increased risk associated with exposure to ionizing radiation (the type of radiation generated by atomic bombs, therapeutic radiation treatment, CT scans, MRI scans, and x-rays) and a decreased risk in persons with history of allergy or other atopic disease (including eczema, psoriasis, and asthma). Recent review articles have further elaborated on the current state of risk factor research in malignant brain tumors.
Heritable Genetic Risk Factors
Several inherited, monogenic mendelian cancer syndromes are associated with increased incidence of glioblastoma, including Lynch syndrome (glioblastoma and other gliomas), Li-Fraumeni syndrome (glioblastoma and other gliomas), melanoma–neural system tumor syndrome (all gliomas), and Ollier disease/Maffucci syndrome (all gliomas). However, these monogenic disorders account for only a small proportion of glioma cases (<5% overall). A small proportion (about 5%–10%) of gliomas occur in familial clusters, in which multiple members of a family have been diagnosed with a glioma. First-degree relatives of patients with glioma have a 2-fold increased risk of developing a brain tumor, and this effect is stronger with family members who are young at the time of diagnosis. Linkage studies within families with multiple patients with glioma have not definitively identified risk variants that are strongly associated with diagnosis of glioma (highly penetrant). In the absence of a clear pattern of risk variants identifiable across many families, segregation analyses suggest that genetic risk factors for glioma are best explained with a multigene (polygenic) model.
Five genome-wide association studies of patients with glioma have been conducted. Together, these studies identified 7 genomic variants that correlated with increased risk of developing a glioma. The variants and their respective genes are telomerase reverse transcriptase ( TERT , rs2736100) ; epidermal growth factor receptor ( EGFR , rs2252586 and rs11979158) ; coiled-coil domain containing 26 ( CCDC26 , rs55705857) ; cyclin-dependent kinase inhibitor 2B ( CDKN2B , rs1412829) ; pleckstrin homologylike domain, family B, member 1 ( PHLDB1 , rs498872) ; tumor protein p53 ( TP53 , rs78378222) ; and regulator of telomere elongation helicase ( RTEL1 , rs6010620). Four of these variants ( TERT , RTEL1 , EGFR , and TP53 ) increase risk of all types of glioma, whereas 3 of these only increase risk for specific grades and histologies of glioma ( CDKN2B , PHLDB1 , and CCDC26 ). Both CCDC26 and PHLDB1 are associated with tumors that have mutations in IDH1 / IDH2 (most often World Health Organization [WHO] grade II and III gliomas), whereas CDKN2B is associated with astrocytic tumors in general (WHO grades II–IV). Two variants in telomere-related genes increase risk for all glioma types (rs2736100 [ TERT ] and rs6010620 [ RTEL1 ]). Telomere length has been associated with other types of cancer, but a recent case-control study did not find a significant overall association between this variant and risk of glioma. A recent review article further elaborated on the current state of heritable genetic risk for glioma.
Glioblastoma subtypes and survival
Primary and Secondary Glioblastoma
Clinical presentation of glioblastoma follows 2 main paradigms: primary glioblastoma, which develops predominantly in elderly adults without previous evidence of a precursor malignancy, and secondary glioblastoma, which occurs mainly in younger patients as a progression from lower-grade glioma. Secondary glioblastomas are rare; a population-based study showed that only 5% of all glioblastomas were secondary. Although indistinguishable histologically, primary and secondary glioblastomas show key molecular differences. EGFR overexpression is observed in many primary glioblastomas, whereas TP53 mutations occur at high incidence in secondary glioblastomas; the mutual exclusivity of these features has suggested distinct pathways for primary and secondary glioblastoma development. More recently, in 2008, mutations in IDH1 / IDH2 mutations as a marker of secondary glioblastoma were reported and have subsequently been shown to be very frequent in secondary glioblastomas and rare in primary glioblastomas (>80% and <5%, respectively). A population-based study showed that only 3.4% of primary glioblastomas carried an IDH1 mutation, and that these patients were younger than their counterparts with secondary glioblastoma, had frequent mutation of TP53 , and lacked amplification of EGFR , suggesting that glioblastomas with isocitrate dehydrogenase 1/2 ( IDH1 / IDH2 ) mutations diagnosed as primary glioblastomas may be misclassified secondary gliomas ( Table 2.1 ). It has been proposed that IDH1 / IDH2 mutation status rather than clinical history can be used as a more reliable marker of primary and secondary glioblastoma for the purposes of prognosis and treatment. IDH1 / IDH2 mutations in glioblastoma are prognostically significant; patients with IDH1 / IDH2 mutations had a median overall survival of 94 weeks versus 31 weeks for those patients without mutations in IDH1 / IDH2 . In addition, lower-grade gliomas that lack mutations in IDH1 / IDH2 have significantly shorter survival times, and seem to be more glioblastomalike.
Related posts:
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Radiographic Detection and Advanced Imaging of Glioblastoma
Awake Craniotomy for Glioblastoma
Brain Plasticity and Reorganization Before, During, and After Glioma Resection
Lessons Learned: Clinical Trials and Other Interventions for Glioblastoma
Recurrent Glioblastoma
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