Meningioma- Management

1. MANAGEMENT
OF
MENINGIOMA
DR KIRAN KUMAR BR

2. INDRODUCTION
• Meningiomas account for approximately 30% of all
intracranial tumors.
• Most common benign intracranial tumor in adults.
• The peak age of incidence is in the sixth and seventh
decades, although they may occur at any age.
• They are more common in women.

3. • Meningiomas are believed to arise from epithelioid
cells on the outer surface of arachnoid villi in the
meninges, also known as arachnoidal cap cells.
• Although as few as 2% of primary BMs undergo
malignant transformation, 28.5% of all recurrences of
BMs are found to be atypical or malignant.

4. ETIOLOGY
• Idiopathic
• Ionizing radiation, has been strongly implicated in the pathogenesis of
these tumors.
• Some relationship with breast cancer may exist, because the likelihood of
the development of a meningioma after having breast cancer, or the
development of breast cancer after having meningioma, is higher than in
the general population.
• The NF2 gene also appears to have an important role in the
pathogenesis of sporadic meningiomas. One study found NF2 mutations
in 60% of sporadic meningiomas, all of which had lost one copy of
chromosome 22

5. • The female predilection of meningiomas suggests that
female sex hormones may also be a risk factor for
tumor genesis.
• Tumors expressing progesterone receptors (PR+)
behave in a more benign clinical fashion and are less
likely to recur.
• Those expressing estrogen receptors or lacking
progesterone receptors display more frequent
genotypic alterations and karyotype abnormalities
consistent with more aggressive meningiomas.

6. CLINICAL FEATURES
• Tumors produce symptoms by one of four major mechanisms:
 (1) local pressure from tumor mass and/or edema disrupting
function of adjacent normal tissue;
 (2) intracranial hypertension due to mass, ventricular outlet
obstruction (e.g., posterior fossa meningiomas), or dural venous
sinus obstruction (e.g., parasagittal meningiomas);
 (3) compression, infiltration, and destruction of neurons;
 (4) hypersecretory syndromes, specifically in the case of
functional pituitary adenomas, due to overproduction of
pituitary hormones.

7. CLINICAL PRESENTATION
•Intracranial meningioma
•A variety of presenting features depend primarily on
•the tumor’s size and
•Location
•These features include
•headache,
•paresis,
•seizure,
•personality change or confusion, and
•visual impairment.
•Headache and paresis are the most common symptom and sign

8. • Olfactory groove have been associated with the
Foster–Kennedy syndrome
• Anosmia,
• ipsilateral optic atrophy, and
• contralateral papilledema
• Tuberculum sellae meningiomas may cause
significant and early visual loss
•typically a “chiasmal syndrome” with ipsilateral optic atrophy and
an incongruent bitemporal hemianopia

9. •Cavernous sinus meningiomas may result in
•proptosis,
•diplopia, or
•primary aberrant oculomotor regeneration;
•Foramen magnum tumors often have associated
•nuchal and suboccipital pain with
•stepwise sensory and motor deficits.

11. INVESTIGATIONS-RADIOLOGICAL
• Meningiomas can be diagnosed by MRI and additional CT
in most cases
• Using these classic criteria, MRI has a sensitivity and
specificity of 98% and 97%, respectively.
• They usually present as solitary round tumours, with close
contact to the dura mater and strong enhancement after
contrast injection.
• MR spectroscopy, meningiomas by identifying an alanine
peak (unique to meningiomas) and an increased
glutamate/creatine ratio

14. CT IMAGING
• CT is valuable for the detection
of calcifi cation within the
tumour, hyperostosis of
adjacent bone, and
intraosseous tumour growth,
especially in skull-base
meningiomas.
• Conventional cerebral
angiography has no routine role
in the diagnosis of meningioma,
but can be used as an adjunct
to treatment planning in
selected cases.
• CT imaging showing hyper
ostosis

15. OCTREOTIDE SCAN
• Meningioma cells strongly express somatostatin
receptor subtype 2 (SSTR 2) which offers an additional
positron emission tomography (PET) based imaging
for tumor delineation with the somatostatin-receptor
ligand [68Ga]-DOTA-D Phe1-Tyr3-Octreotide
(DOTATOC) .
• DOTATOC-PET/CT shows a high meningioma to
background ratio which can be used to improve target
volume definition prior to IMRT

16. • MR spectroscopy: usually it does not play a significant
role in diagnosis but can help distinguish
meningiomas from mimics. Features include:increase
in alanine (1.3-1.5 ppm)
increased glutamine/glutamate
increased choline (Cho): cellular tumour
absent or significantly reduced N-
acetylaspartate (NAA): non-neuronal origin
absent or significantly reduced creatine (Cr)

17. 2016 WHO CLASSIFICATION

18. WHO 2016 GRADING
• GRADE I: Low mitotic rate <4 / 10 HPFs
• Absence of brain invasion
• 9 subtypes
• GRADE II (ATYPICAL) : Mitotic rate 4-19/ HPF
• Brain invasion
• 3 of 5 specific histology : prominent nucleoli , high cellularity ,
spontaneous necrosis , sheeting and small cells
• Grade III : mitotic rate > 20/HPF
• Specific histologies : papillary or rhabdoid meningioma

20. PROPOSED MOLECULAR
CLASSIFICATION

21. MANAGEMENT
• (1) observation,
• (2) open microsurgery,
• (3) stereotactic radiosurgery,
• (4) fractionated radiotherapy (XRT), or fractionated
stereotactic radiotherapy (FSRT),
• (5) chemotherapy, or combinations

22. GRADE 1 MENINGIOMA
• Observation is appropriate for some, especially small tumors that are incidentally
discovered.
• Asymptomatic with size < 30mm.
 T2 hyperintensity,
 lack of calcification,
 size greater than 25 mm, and
 edema are associated with a shorter time to progression, and those tumors should
be followed more closely
• Oya S, Kim SH, Sade B, et al. The natural history of intracranial meningiomas. J
Neurosurg 2011;114:1250–1256.

23. SURGERY
• Surgery remains an appropriate therapy for many
meningiomas.
• Convexity meningiomas are often managed with
resection because they can typically be
completely resected without significant
morbidity.
• The goal is total resection, including a dural
margin, because this is often curative for WHO
grade I tumors.

24. GRADES OF RESECTION

25. COMPLICATIONS
• Easily accessible tumors, are amenable to complete
resection and associated with low morbidity (10% of
patients with neurologic sequelae) and mortality (0 to
3%).
• When compared to morbidity of 18-86% for tumours
that are inaccesible
• Factors increasing mortality include poor preoperative
clinical condition, compressive symptoms from tumor,
older age, incomplete tumor removal, pulmonary
embolism, and intracranial hemorrhage

26. OBSERVATION
• The morbidity of surgery can be quite significant;
• The majority of incidental meningiomas show minimal
growth.
• Age over 70years, tumor growth is associated with
patient age, with tumors in younger patients having a
shorter doubling time than in older patients.

27. • Tumors that cannot be totally excised because of their
adjacency to critical structures such as cranial nerves
and sinuses
• (e.g., medial sphenoid wing, petroclival, clinoidal, and
tentorial-based tumors, and posterior parasagittal
lesions, respectively) therefore are at highest risk for
tumor recurrence.
• Hence Radiation therapy is indicated.

28. ADJUVANT RADIATION
• Benign subtotally resected tumors had significantly
improved rates of PFS (93% vs. 65% at 10 years) when a
dose greater than 52 Gy was delivered.--Goldsmith and
colleagues.
• In a series by Taylor and associates,20 the local control
benefit of postoperative radiotherapy at the time of first
recurrence (88% vs. 30% at 5 years) translated into an OS
benefit (90% vs. 45% at 5 years).
• Dose of 45Gy-54GY at 1.8-2Gy/Fx

29. SRS
• Stereotactic radiosurgery is considered most effective
for patients with
small meningiomas, typically those that are less than 3
cm in diameter or 10 cm3 in volume, (DiBiase and
colleagues , Kondziolka et al)
 those with distinct margins, and
 those at sufficient distance from functionally
important brain, nerves, and other critical structures to
permit safe delivery of an adequate target dose.

30. • Pollock and colleagues found 10-year local control was
99.4%, using a mean tumor margin dose of 15.8 Gy.
• No patient developed marginal recurrence.
• These results suggest that Grade I meningioma can often
be accurately defined and well controlled with SRS as
primary therapy.
• DOSE : 12-16 Gy in single fraction
• Ganz and colleagues , Stafford et al.

31. SRT
• Girvigian et al. study involving 30 patients with convexity or
parasagittal meningiomas, 14 treated with single-fraction and
16 with multifraction SRS.
• Symptomatic edema occurred in 43% following single-fraction
SRS, as opposed to 6.3% (1 patient) after multifraction SRS,
• Single doses of more than 14 Gy and larger tumor volume
were predictors of edema. (Neurosurgery 62:5 SupplA19–
A28, 2008)
• Unger et al. reported on 173 patients and found that
symptomatic edema was significantly less common following
multifraction SRS (typically 25 Gy in 5 fractions) than single-
session SRS (median 15 Gy); (Neurosurgery 70:639–645, 2012)

32. GRADE II MENINGIOMA
MANEGEMENT
• constitute 20%–35% of newly diagnosed
meningiomas.
• Surgery is the first choice of treatment and should aim
to achieve Simpson grade I resection
• While adjuvant RT is standardly used at many
institutions after subtotal resection (STR) of Atypical
Meningioma, its role after GTR is controversial.
 Mair R, Morris K, Scott I, Carroll TA. Radiotherapy for
atypical meningiomas. J Neurosurg. 2011;115(4):811–
819. [PubMed]

33. ADJUVANT RT
• Some have recommended EBRT irrespective of resection
extent, but others have questioned its benefit.
• Komotar et al. reported on 45 patients with atypical
meningioma who received a Simpson Grade 1 or 2 resection.
• Following GTR alone versus GTR and EBRT, the respective 6-
year actuarial recurrence risks were 65% versus 20% (p =
0.085).
• Park et al. reported 5-year PFS rates of 46.4% with GTR alone,
77.9% with GTR and EBRT, 0% with STR alone, and 55.6% for
STR and EBRT. (Atypical meningioma: outcome and prognostic
factors. Int J Radiat Oncol Biol Phys 75:S238, 2009)
• Progression free survival was improved by EBRT, regardless of
the extent of resection.

34. DOSE
• For grade II meningiomas recommended dose is
54Gy-60 GY at 1.8Gy-2 Gy per fraction
• Directed to gross tumour if present , or with margin of
1cm-2cm along with surgical bed

35. SRS

36. CHEMOTHERAPY
• The most promising results have been
reported for bevacizumab, vatalanib, and
sunitinib—
• All drugs with antiangiogenic properties.
• These results need to be confirmed in
prospective controlled trials before clinical
use of these compounds in WHO grade II and
III meningiomas can be recommended.

37. ANAPLASTIC MENINGIOMA
• Less than 3% of newly diagnosed meningiomas are WHO Grade
III (also termed anaplastic or malignant).
• These are aggressive tumors with considerably poorer local
control and overall survival than lower grade meningiomas.
• In most cases of aggressive meningioma, surgery serves as the
first-line therapy and helps establish a diagnosis.
• the success of surgery alone has not been satisfactory.
Jääskeläinen et al. reported a 5-year recurrence rate of 78%
following GTR for patients with anaplastic meningioma, less than
half of whom received any adjuvant therapy

38. SURGERY
• When a clear plane between the tumor and surrounding
normal structures can be identified, GTR remains the goal
of surgery for anaplastic meningioma.
• improved overall survival with near-total resection as
opposed to GTR; near-total resection implied greater
than 90% tumor removal.
• They found that aggressive surgical efforts did not
improve survival, and even compromised neurological
outcome.
• Surgery appears to be beneficial at recurrence as well.
Correcting for other prognostic factors, Sughrue et al.

39. FRACTIONATED RADIATION
THERAPY
• Dziuk et al. found that EBRT improved 5-year PFS
from 50% to 80% compared with surgery alone.
• When EBRT was added following initial resection,
5-year PFS significantly improved from 15% to
80%.
• Milosevic et al. found that patients who received
< 50 Gy experienced inferior cause-specific
survival,.

40. • In the EORTC 22042-26042 trial, WHO grade II and III tumours
were irradiated with 60 Gy in 30 fractions subsequent to gross
total resection.
• After subtotal resection, 60 Gy plus a 10 Gy boost on the
remaining tumour volume were delivered. Results are pending.
• RTOG 0539 trial ,in which WHO grade II meningiomas are being
treated by radiotherapy with 54 Gy in 30 fractions after gross
total resection,
• whereas high-risk meningioma (ie, WHO grade II recurrent
disease, WHO grade II after subtotal resection, and all WHO
grade III) are receiving up to 60 Gy.

41. SRS
• Pollock and colleagues studied 50 WHO Grade II or III patients,
treated in both the de novo and salvage settings.
• Thirteen patients had anaplastic meningioma.
• Their median treatment volume was larger at 14.6 cm3, and the
median dose was modestly higher at 15 Gy.
• Disease-specific survival rates at 1 and 5 years for the WHO
Grade III patients were 69% and 27%, respectively.
• Pollock BE, Stafford SL, Link MJ, Garces YI, Foote RL: Stereotactic
radiosurgery of World Health Organization grade II and III
intracranial meningiomas: treatment results on the basis of a 22-
year experience. Cancer 118:1048– 1054, 2012

42. RADIOTHERAPY
• Primary radiotherapy (RT)  Indicated for :
- Tumors in locations in which complete
resection is not feasible (i.e., optic nerve,
cavernous sinus, major venous sinus)
- Patients who are poor surgical candidates.
• Adjuvant RT  Indicated for :
- Patients with subtotal resection (STR),
- Recurrent disease,
- WHO grade II or III tumors (GTR)

43. TARGET DELINEATION GRADE I
• The GTV is the enhancing disease based on the T1 postgadolinium MRI, and the T2
FLAIR imaging can assist in delineating disease.
• The inclusion of the dural tail is controversial; however, if toxicity is not signifi cantly
increased as a result of its inclusion, then it is typically taken in the volume.
• A CTV ranging from 0 to 0.5 cm may be applied and depends on the clinical
situation.
• PTV consists of the clinical tumor volume (CTV) plus a margin of 5 mm for conventional
mask immobilization or 2 to 3 mm for stereotactic frame-based immobilization technique.
• GTV=PTV in SRS

44. • Planning CT scans obtained with proper head
immobilization is fused with a diagnostic T1-weighted
MRI for optimal target delineation,
• For grade II and III tumors, the surgical bed is included
in the GTV contour, and a CTV ranging from 0.5 to 1
cm that respects anatomic barriers to tumor.
• the CTV margin should account for contiguous spread
into the adjacent brain tissue, unlike grade I tumors,
due to the potential for brain invasion

45. • Atypical and anaplastic meningioma :
CTV : 10 mm beyond GTV, operative bed,
hyperostotic bone, and dural thickening.

47. FOLLOW UPS
• Asymptomatic meningiomas:
MRI with contrast medium 6 months after initial
diagnosis, and
 then annually as long as the patient remains
asymptomatic.
After 5 years, this interval can be doubled.

48. GRADE I
• For WHO grade I meningiomas resected totally,
10-year recurrence varies from 20% to 39%.
• a baseline MRI within 48 h or after 3 months is
advised to assess the extent of resection.
• STR : MRI at 6 months and 12 months and then
annually
• GTR : annual MRI till 5 yyears and then once in
years

49. GRADE II
• The 5-year recurrence or progression could be as high
as 30% after gross total resection and 40% after
subtotal resection.
• Baseline MRI after 48hrs after ressection
• MRI every 6 months for first 5 years and then annually.

50. GRADE III
• For WHO grade III meningiomas, the 5-year
progression-free survival ranged from 12% to 57%,
even after resection and radiotherapy.
• Cranial imaging every 6 months , or if rapidly
progressing , every 3 months.

52. PRIMARY REFERENCES
• Meningiomas: knowledge base, treatment
outcomes, and uncertainties. A RANO review
Leland Rogers, MD, Igor Barani, et al
J Neurosurg 122:4–23, 2015
• EANO guidelines for the diagnosis and treatment
of meningiomas Roland Goldbrunner, Giuseppe
Minniti, Matthias Preusser Lancet Oncol 2016; 17:
e383–91.