http://humanhealth.iaea.org
Collection of Recorded Radiotherapy Seminars
IAEA Human Health Campus
McGill
The Role of Radiotherapy in
Meningiomas
Dr. Luis Souhami
Professor
Department of Radiation Oncology
McGill University – Montreal, Canada
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Meningiomas - Facts
• Most common CNS tumor
Claus EB et al Neurosurgery 2005Central Brain Tumor registry – USA 2010
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Meningiomas - Facts
• 30% primary tumors (38% females)
• 35-60% diagnosed by imaging
• Identified in 2.5% of autopsies
• 70% have progesterone receptors
• 30% have estrogen receptors
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Meningiomas - Facts
• Arise from arachnoid caps cells or
meningothelial progenitor cells
• WHO classification 2007
– Benign meningiomas (grade 1)
– Atypical (grade 2)
– Anaplastic (grade 3)
15-25% are histologically atypical or anaplastic
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WHO Classification - 2007Rodgers L et al.
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Prognostic factors
• Histopathology (tumor grade) – Mitotic activity
– Hypercellularity
– Nucleolar prominence
– Necrosis
– Brain invasion
– Loss of meningothelial differentiation
• Surgical procedure– Total resection
– Sub-total resection
Perry A. et al. Am J Surg Pathol 1997
Korshunov A et al. Int J Cancer 2003
Perry a et al. Cancer 1999
Simpson grades of resection(Simpson D: J Neurol Neusosurg Psychiatry 1957)
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Surgical Intervention
Rogers & Mehta. Neurosurg Focus 2007
Stafford et al. Mayo clinic proceedings 1998
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Not necessarily an inoffensive disease
Disease-free survival
Perry A – Pathology of tumors of the CNS 2006
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RTOG Risk Stratification
LOW RISK INTERMEDIATE RISK HIGH RISK
WHO Grade 1 Recurrent grade 1 Recurrent Grade 2
GTR or STR WHO Grade 2 (even with GTR) WHO Grade 3
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Management of Meningiomas
• Surgery is the standard treatment
– Radical resection provides long-term DFS
• Certain meningiomas cannot be
completely excised
– How should they be managed?
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Benign Meningiomas (WHO grade 1)
• 70-85% of meningiomas. Slow grow
• Local control in 10 yrs: 80-85%1-3
– Complete surgical removal
• Incomplete resection –
– Local failure: 30-60% in 5-10 yrs4,5
– Patients may remain well for many years
Condra KS et al. IJROBP 19991, Nutting C et al. J Neurosurg 19992, Perry A et al. Cancer 19993
Mirimanoff R et al. J Neurosurg 19854, Milker-Zaber S et al. IJROBP 20055
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“Rule of Thumb”
5 yr 10 yr 15 yrGTR 10% 20% 30%
STR 30% 60% 90%
Failure Rate
Adegbite et al J Neurosurg 1983
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Should incompletely resected grade 1
meningioma receive post-op RT?
• Several retrospective studies show benefit of RT
Author N°°°° Pts GTR STR RTMirimanoff 225 93% 63%
Taylor 132 96% 43% 85%
Adegbite 114 90% 45% 82%
Barbaro 135 96% 60% 80%
Mahmood 254 98% 54% 67%
Condra 262 95% 83% 86%
Soyuer 92 77% 38% 91%
Goldsmith 92 89%
98% after 1980
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Should incompletely resected grade 1
meningioma receive post-op RT?
• Re-growth is slow
• Further surgery can be performed
• Fear of radiation-induced toxicity
Planimetric: 2.0%/year
Volumetric: 5.8%/year
p=
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Are there markers to predict
recurrence of benign meningiomas?
Abdelzaher E et al. Br J Neurosurg 2010
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Should incompletely resected grade 1
meningioma receive post-op RT?
• Patients have a shorter life expectancy– After STR relative risk of death is 4.2 times greater than with GTR
• Recurrences have detrimental effect on survival
• Data from American College of Surgeons and
American Cancer Society – 8900 pts – 5 yr survival of 70% (56% in pts >65yrs)
• Recurrence in certain locations can have
devastating effect on quality of life
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EORTC tried to answer question
WHO Grade 1 Meningiomas incompletely resected
RANDOMIZE
Post-op RT
Observation
Modern Radiation Therapy
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Atypical MeningiomasWHO Grade 2
• Less common – (15-25%)1-3
• Risk of recurrence post-surgery higher1-6
– 7-8 fold increased risk in 3-5 yrs
– Only 40-60% disease-free at 10 yrs
• Role of RT also controversial
Perry A et al Cancer 19991
Perry A et al Am J Surg Path 19972
Perry A al WHO 20073
Jaaskelaine J et al Surg Neurol 19864
Perry A Surg Neurol 20045
Hug EB et al J Neurooncol 20006
35 yr. old, female
July 2010 – seizure episode (arm + face)
September 2010 – GTR, atypical meningioma
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Meningiomas - Outcomes
Recurrence-free Survival Overall Survival
Perry A – Pathology of tumors of the CNS 2006
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Outcomes in Atypical Meningiomas
Author N° Pts Local5 yr
Recurrence
15 yr
CSS
Condra 47 38% 46% 57% (15 yr)
Aghi 108 41% 69% (10 yr)
Surgery Alone
Condra KS et al. IJROBP 1997
Aghi MK et al. Neurosurgery 2009
GTR (Simpson grade 1)
Aghi et al
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RTOG Risk Stratification
LOW RISK INTERMEDIATE RISK HIGH RISK
WHO Grade 1 Recurrent grade 1 Recurrent Grade 2
GTR or STR WHO Grade 2 (even with GTR) WHO Grade 3
On-Going StudiesRTOG
EORTC
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Anaplastic Meningiomas
• Aggressive behaviour
• Adjuvant radiation therapy recommended
– Minimum dose: 60 Gy
Combs SE et al. Int J Radiat Oncol Biol Phys 2010 (in press)
WHO 1993 WHO 2007
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Modern Radiation Therapy
• 3-Dimensional Radiation Therapy
– Intensity modulated radiation therapy (IMRT)
– Fractionated stereotactic radiation therapy
(FSRT)
– Stereotactic radiosurgery (SRS)
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Modern Radiation Therapy
• Goldsmith et al. (J Neurosurg 1994)
– 117 pts treated at UCSF
– 5-yr PFD of 98% with 3-DRT compared to 77%
for pts treated before 1980
• Mendenhall et al. (Cancer 2003)
– 107 pts treated at U. of Florida
– Local control at 5-yr of 95% with 3-DRT
25/Dec/2005 7/Mar/2007
44 female. Lump in scalp in 2004.
Seen by neurosurgery in 2005.
Kept under observation.
Taken to the OR in 2008.
Pathology: meningioma grade 1
3/Nov/20087/Mar/2007
Pre-op Post-op
54 Gy
50.4 Gy
30 Gy
3/Nov/2008 17/Aug/2010
Post-op Post-IMRT
64 female
eye sight 2004 (MRI = meningioma). Further deterioration in 2007
2007: eye sight, size meningioma
April 2008: surgery elsewhere (carotid, cavernous sinus, RT optic canal
2009: vision worse. Referred to RT
52 Gy
35 Gy
Chiasm
RT optic N
Brainstem
LT optic N
54 Gy
40 female. Suprasellar meningioma 2006STR 20072008 in size2009 referred for RT
Chiasm
Brainstem
LT optic N
RT optic N
54 Gy51.3 Gy
40.5 Gy
30 Gy
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Treatment ParametersConventionally Fractionated RT
• Doses above 55 Gy not associated with
better control (WHO Grade 1)
• Doses below 50 Gy associated with
increased failure rates
• Anaplastic meningiomas should receive
dose of ≥60 Gy
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Treatment Parameters
Conventionally Fractionated RT
• Target Volume
– GTV – ideally contoured using MRI (CT to
visualize bony structures)
– CTV – margin expansion of 1 cm for grade 1
and 1.5 cm for higher grades
• Dural tail only included if nodular or
abnormally thickened
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Stereotactic Radiosurgery
• Selected patients
• Tumors ≤4 cm, distinct margins• Tumors not close to vital structures
(chiasm, brainstem, etc)
• Doses between 12 and 16 Gy frequently
used
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Stereotactic Radiosurgery
Results
Rogers & Mehta. Neurosurg Focus 2007
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Fractionated Stereotactic
Radiotherapy
• Involves the delivery of fractionated course
of RT using a relocatable immobilization
device
• Uses same principles of SRS (stereotaxis
and stabilization)
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Fractionated Stereotactic
Radiotherapy
• Advantageous for tumors near or at critical
areas
• Similar control rates of SRS
• Less complications (?)
Fractionated Stereotactic Radiotherapy
Top: Conventional 3-field technique ( PTV + chiasm covered by 95%)
Bottom: 5-field FSRT (PTV covered by 100%; chiasm by 75%)
Chiasm
Chiasm
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Conclusions
• Meningiomas represent a spectrum
• Use of post-op RT remains controversial
• Grade 1, GTR (?STR) should be observed
• Atypical and anaplastic meningiomas are
more aggressive
• Conventionally fractionated IMRT or SFRT
are good options for large, irregular
meningiomas near critical structures
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Conclusions
• Conventionally fractionated IMRT or SFRT
are good options for large, irregular
meningiomas near critical structures
• Small lesions can be safely treated with
SRS (control rates: 75-100%)
• On-going studies (RTOG, EORTC)
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