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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

McGill

Meningiomas - Facts

• Most common CNS tumor

Claus EB et al Neurosurgery 2005Central Brain Tumor registry – USA 2010

McGill

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

McGill

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)

McGill

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

McGill

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

McGill

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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• 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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• 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

McGill

Meningiomas - Outcomes

Recurrence-free Survival Overall Survival

Perry A – Pathology of tumors of the CNS 2006

McGill

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

McGill

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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• 3-Dimensional Radiation Therapy

– Intensity modulated radiation therapy (IMRT)

– Fractionated stereotactic radiation therapy

(FSRT)

– Stereotactic radiosurgery (SRS)

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• 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

McGill

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

McGill

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

McGill

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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