Epidemiology of Meningiomas in England

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Epidemiology of Meningiomas in England Tina Karabatsou 1, David Greenberg 2, Sarah Miller 2, Andy Brodbelt 4, Matt Williams 3 & Peter Collins 5 1 Salford Royal Hospital NHS Foundation Trust, Manchester 4 The Walton Centre NHS Foundation trust, Liverpool 2 NCIN, Public Health England 3 Imperial Hospitals NHS Foundation Trust, London 5 Cambridge University On behalf of NCRAS

Background Meningiomas are considered to be mostly benign CNS tumours, however not infrequently they can manifest more aggressive features and the morbidity associated with them can lead to serious consequences for the quality of life and life-expectancy of the individuals affected by them.

What did we know so far? Meningiomas represent approximately 2 of all symptomatic intracranial tumors (DeMonte and Al-Mefty 1995). Meningiomas occur at a rate of 7.8 in 100,000 per year, and only 25% of these (2 in 100,000 per year) are symptomatic on presentation (Radhakrishnan et al 1995).

Design To review the incidence and survival rates of meningiomas in England A population-based study linking data from the National Cancer Registration Service with Hospital Episode Statistics for England, to identify patients diagnosed with a meningioma Subjects: All patients diagnosed with a meningioma in England between 1999-2013

Methods Demographic data, tumour behaviour, initial treatment patterns, and survival rates were evaluated using surveillance epidemiology statistical methods

Results 24284 cranial (70,8% Females) and 1390 spinal (77.1% Females) meningiomas of all grades were diagnosed. Median age at diagnosis 65 years 64% were diagnosed histologically, 22% on imaging and 14% other 88% are WHO grade I, 7% grade II and 5% grade III

Meningiomas in England 1999-2013 1. Tumours diagnosed in residents of England 1999-2013 SUBSITE BEHAVIOUR_ICD10_O2 Total Male Female Cranial_meninges 0: ~ WHO Grade 1 21490 5954 15536 Cranial_meninges 1: ~ WHO Grade 2 1656 699 957 Cranial_meninges 3: ~ WHO Grade 3 1138 434 704 Spinal_meninges 0: ~ WHO Grade 1 1244 263 981 Spinal_meninges 1: ~ WHO Grade 2 61 25 36 Spinal_meninges 3: ~ WHO Grade 3 85 30 55 Cranial_meninges all grades 24284 7087 17197 Spinal_meninges all grades 1390 318 1072 All_meninges all grades 25674 7405 18269

Number of cases Meningiomas (all sites and WHO grades) diagnosed in England residents 1999-2013 by tumour location and basis of diagnosis 12000 10597 10000 8000 6000 4000 4105 4668 Male Female 2000 0 541 208 Death Cert 613 1647 1471 6 12 Clinical Imaging Hist of Mets Cranial meninges HistologyUnknown 127 308 3 7 1631 1759 Death Cert Clinical Tumour location and basis of diagnosis 275 971 Imaging HistologyUnknown Spinal meninges 8 5

Results (Cranial meningiomas) For all cranial meningiomas 5 and 10-year survival are 73% and 68.1% in grade I, 78.4% and 68.5% in grade II 45, 4% and 39% in grade III. Postoperative 5 and 10 year survivals for cranial meningiomas were improved at 90.7% and 86.9% in grade I, 84, % and 75.1% in grade II and 62.2% and 54. 1% in grade III respectively The age -standardized annual incidence has increased from 1,5 in 1999 to 3 per 100.000 population in 2013

Directly age-standardised rate per 100,000 population WHO grade 1 cranial meningioma age stanardised incidence rates in England, by period of diagnosis and gender, 1999-2013 4 3.5 3 2.5 2 Males Females Persons 1.5 1 0.5 0 1999-2003 2004-2008 2009-2013 Period of diagnosis

Relative survival Meningiomas are a moderately long survival tumour so we cannot use survival metrics such as median survival because >5 of cases are still alive and we should not use Kaplan Meier survival because a high proportion of patients are quite elderly at diagnosis and would have reduced life expectancy in the absence of disease So Relative survival is generally used in epidemiological studies. Relative survival is defined as the ratio of the proportion of observed survivors in a cohort of cancer patients to the proportion of expected survivors in a comparable set of cancer free individuals. This is generally the overall population matched by age, sex, region of residence, deprivation.

Percent relative survival Relative survival for meningiomas (all sites and WHO grades) diagnosed in England residents 1999-2013 12 10 Brain _pilocytic_astrocytoma (GI) Cranial_meninges GI 8 Cranial_meninges GII 6 Cranial_meninges GIII Spinal_meninges GI 4 Spinal_meninges GII 2 Spinal_meninges GIII 0 1 2 3 4 5 6 7 8 9 10 Survival in years

Percent relative survival Relative survival for WHO Grade I cranial meningiomas diagnosed in England residents 1999-2013 by gender 10 9 8 7 6 5 Male Female 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 Survival in years

Relative survival for histologically diagnosed WHO Grade I cranial meningiomas diagnosed in England residents 1999-2013 by gender M F 0 1 2 3 4 5 6 7 8 9 10 Survival in years

Relative survival for cranial meningiomas diagnosed in residents of England 1999-2009 (5 year survival) or 1999-2004 (10 year survival) Survival years Basis of diagnosis Cranial meninges GI Cranial meninges GII Cranial meninges GIII Histologically 5 confirmed only 90.7% 84.6% 62.2% 5 All cases 73. 78.4% 45.4% Histologically 10 confirmed only 86.9% 75.1% 54.1% 10 All cases 68.1% 68.5% 39.

Percent relative survival Relative survival for WHO Grade I cranial meningiomas diagnosed in England residents 1999-2013 by gender and basis of diagnosis 10 9 8 7 6 5 4 Male- Histological Female- Histological Male-All combined Female-All combined 3 2 1 0 1 2 3 4 5 6 7 8 9 10 Survival in years

Age standardised incidence rates per 100,000 population for Grade 1 cranial meningiomas Year of diagnosis Males Females Persons 1999-2003 1.11 1.72 1.51 2004-2008 1.99 3.19 2.78 2009-2013 2.11 3.45 3.00

The american data: Epidemiology of meningiomas post-public Law 107-206: The Benign Brain Tumor Cancer Registries Amendment Act. The average annual age-adjusted incidence rate per 100,000 population was 7.62 for all meningiomas, 7.18 for benign meningiomas, 0.32 for borderline malignant meningiomas, and 0.12 for malignant meningiomas Diagnostic confirmation through pathology occurred for approximately 5 of benign tumors, 9 of borderline malignant tumors, and 8 of malignant tumors. No initial treatment was reported for greater than 6 of benign tumors, 29% of borderline malignant tumors, or 31% of malignant tumors.

The american data: The 5-year relative survival estimates for benign tumors, borderline malignant tumors, and malignant tumors were 85.6%,82.3%, and 66% respectively. Predictors of poorer survival were advanced age, being male gender, black race, no initial treatment, and malignant tumor behavior Cancer. 2015 Apr 14. Dolecek TA1, Dressler EV, Thakkar JP, Liu M, Al-Qaisi A, Villano JL.

Conclusion Even in 'benign' (WHO grade 1) cranial meningioma patients, 5 year survival is 73% Our analysis demonstrates an increasing incidence of meningiomas, maybe due to increased reporting and ageing population. Patient survival has improved over time, and is it remains better for surgically treated meningiomas, and poorer for older people.

Limitations Limitations of the present study include the lack of detailed data re: tumour site (i.e. skull base) Comorbidities Radiotherapy, SRS, chemotherapy Data on recurrences. Morbidity Further data sub-analysis on the way.