Epidemiology of Meningioma: Whats New

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Epidemiology of Meningioma Whats New?

• Elizabeth B. Claus, Ph.D., M.D
• BWH 5/5/2006

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Sponsor Brain Science Foundation
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BACKGROUND Some facts about Meningioma (CBTRUS)

• 13,000 new cases expected per year in the United
  States.
• Almost 150,000 prevalent cases of meningioma
  estimated in 2005.
• Rate in women is twice that in men.
• Rate is similar across race.
• Median age at diagnosis is 64.

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Proportion of Primary Brain Tumors by Histologic
Type (CBTRUS 2002)
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Classification

• Meningioma (gt90)
• Borderline/
• atypical (5)
• Malignant (lt5)

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Age-Specific Incidence Rates of Meningioma by
Age at Diagnosis
Rates are per 100,000 person-years (CBTRUS 2002)
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CBTRUS 2003-03
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CBTRUS 2002-03
White and Black rates 1995-1999, 12 registries
Hispanic rates 1998, 16 registries
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Time Trends (Intl J Cancer 2005)

• U.S. data limited
• Incidence rates have increased in Scandinavia
  (1968-1997)
• Some increase likely due to increased detection
  via CT scans
• Femalemale ratio increased for some age-groups
  (i.e. 40-44 years)-may suggest increasing use of
  hormones affects incidence?

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Data from the state of Massachusetts 1998 (CBTRUS)

• 183 meningiomas reported (based on pathology
  report)
• 148/183 Female
• 166/183 White

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Treatment

• Surgery
• Radiation therapy
• Adjuvant therapy such as anti-estrogens?

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Outcomes Overall Survival Rates for Meningioma.
Connecticut and Utah 1985-94

• 2-year 84
• 5-year 73
• 10-year 55

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Quality of Life Issues

• Many patients have difficulties with
• Speech
• Concentration
• Weakness
• Writing
• Driving

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Risk Factors for Meningioma

• Hormones
• - Women at greater risk
• - Some tumors have hormone receptors
• - Hormone replacement therapy (HRT)
• - Unclear association with oral
  contraceptives

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Risk Factors for Meningioma

• Hormones
• - Some tumors may change in size during
  pregnancy and menstrual cycle
• - Possible association with breast cancer

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Hormone Receptors-Estrogen

• Prevalence 0- 94
• Data by subtype (age, sex, histology, receptor
  isoform) not well defined
• Current use of tamoxifen in meningioma equivocal-
  need better characterization of candidates

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Hormone Receptors-Progesterone

• Prevalence 40-100
• Evidence for role from mice implanted with human
  meningioma. One group of these mice received
  anti-progesterone mifepristone (RU486) while the
  other group received placebo. After three months,
  the tumor volume was 154 of baseline in the
  control group and 25 of baseline in the treated
  group.

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Exogenous/Endogenous Hormones (Nurses Health
Study)
No associations found in other
studies RRrelative risk CIconfidence interval
NHSNurses Health Study
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Association with Breast Cancer

• No evidence of BRCA1 or BRCA2 mutations in 38
  cases of sporadic meningioma
• Tumor registry studies show 1.5 to 2.0-fold RR
  for meningioma and breast cancer
• Overlap of risk factors

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Brain Tumors-Cell Phone Use Update

• At least 10 completed studies to date
• None show association in the short term
• Further study needed-new types of phones
  (digital), longer exposure times

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Interphone Study

• Case/control study (Swedish and German portions)
• Outcomes meningioma, glioma, parotid gland,
  acoustic neuroma
• No evidence of short term effect
• gt10 year no evidence to date

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Exposure Still of Interest
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Head Trauma

• Postulated since time of Harvey Cushing
• Confounded with diagnostic method
• Many and studies
• Danish study of 228,055 people hospitalized for
  head trauma RR1.2 (0.8 1.7)

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Ionizing Radiation
Tinea Capitas Atomic bomb survivors
Treatment for cancer Dental x-rays some and
studies (dose similar to TC study) full mouth
series performed 15-40 yrs ago
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Ionizing radiation and meningioma risk in
children (Sadetski et al, 2005)

• Tinea Capitas Cohort- North African children (n gt
  10000) given radiation therapy for scalp ringworm
  in Israel 1948-60

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Ionizing radiation and meningioma risk in children

• Median dose 1.38 Gy
• Followed Relative risk of meningioma is
  approximately ten-fold, of glioma is 2.6
• New analyses (Sadetski et al 2005)
• Dose associated with risk of both
• Inverse relationship between age and glioma risk
  but not meningioma risk

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What about genetic risk factors?

• Family history of meningioma increases risk 2-3X
• Neurofibromatosis-2 (NF-2) is an inherited gene
  associated with meningioma (This is an example
  where one gene has a very strong effect on
  disease)

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Polygenetic Disorders

• Major genes likely to be rare (1-5)- need to
  examine other genetic causes.
• Generally more common (prevalent) in the
  population (vs single major gene) but less
  penetrant
• May involve a pathway, i.e. DNA repair genes,
  hormone metabolism genes
• Believed to interact with the environment to
  result in disease (geneenvironment)

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Pathways of Interest for Meningioma

• What are some categories of interest?
• DNA repair
• Cell Cycle
• Hormone metabolism

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Gene X Environmental Interaction

• Tumors are likely due to a combination of genetic
  and environmental factors
• Example Individuals with different estrogen
  metabolism genes may interact with OC/HRT
  differently
• NIH goal to use multi-center studies to gather
  these data-large sample size needed.

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Why havent there been more epidemiologic studies
of meningioma?

• 90 of meningiomas are classified as benign
  (rather than Cancer)
• No growth in the brain is benign!

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Why is now the time to advance epdiemiology of
meningioma?

• New legislation passed
• The Benign Brain Tumor Cancer Registries
  Amendment Act (H.R. 5204)

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Future directions

• Need for large-scale, population-based
  epidemiologic studies with good laboratory data,
  uniform pathologic review with histologic
  subtyping, and long-term follow-up of medical and
  lifestyle outcomes.

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New Meningioma Study

• NIH Grant to start this year
• Study design Compare persons with meningioma
  (CASES) to persons without meningioma (CONTROLS).
  
• Collect 1500 cases (1000 female and 500 male) and
  1500 controls (age, sex, ethnicity and geography
  matched)

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New Meningioma Study

• Five population-based study centers Connecticut
  (Yale), Massachusetts (BWH), North Carolina
  (Duke), the San Francisco Bay Area (UCSF) and
  Harris County of Texas (MD Anderson Cancer
  Center).
• Cases must have had surgery (to confirm
  diagnosis) from 5/1/2006 onwards

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Proposed Meningioma Study Aims

• Will include questionnaire and collection of
  tumor and blood specimens
• Formally and comprehensively examine the
  environmental, genetic, pathologic, and clinical
  variables associated with meningioma risk
• Consider quality of life issues for meningioma
  patients

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Strengths and Unique Contributions

• Largest case/control study of meningioma to date
  at least 8-fold larger than any previous work
• First project to examine on a population-based
  scale genetic and epidemiologic risk factors and
  their interactions with meningioma

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Strengths and Unique Contributions

• Timing US Congress has recently passed new
  legislation to include the collection of benign
  tumors in the Public Health Service Act
• Study of brain tumors is a greatly underserved
  area within epidemiology and genetics and we are
  fortunate to have gathered a group of experts in
  cancer, neuro-epidemiology, neurosurgery, and
  genetics.
• Stay tuned!