This seminar is presented as a part of weekly journal club and seminar regularly conducted at Apollo hospital,Kolkata Department of Radiation oncology.

1. EANO guidelines for the
diagnosis and treatment
of meningiomas
DR TANWEER SHAHID
CONSULTANT,RADIATION ONCOLOGY
APOLLO GLENEAGLES HOSPITALS,KOLKATA

2. INTRODUCTION
Meningiomas: MC primary intracranial tumours.
 Classified into grades : WHO grade I,II and III : On the basis of local invasiveness and
cellular features of atypia.
T/T by surgery alone, particularly patients with WHO grade I tumours in favourable
locations (eg, convexity meningiomas, and easily accessible skull-base meningiomas).
Beyond surgery, various radiotherapy approaches are often used to increase local
control, especially if surgery alone seems insufficient

3. Introduction…
• Meningioma : Originates from arachnoid cap cells.
•Account for about one third of all brain tumors (CBTRUS, 2015).
• Incidence increases with age.
•Many histological subtypes and differ in their level of malignant behavior.
•WHO classifies them in 3 grades, which have distinct prognostic properties.
•Malignant meningiomas (WHO grade III) are rare, but aggressive.

4. Cause…
40% and 80% of meningiomas contain an abnormal chromosome 22. This chromosome is
normally involved in suppressing tumor growth. The cause of this abnormality is not known.
Previous radiation to the head.
History of breast cancer.
NF type 2 :Multiple meningiomas.
Hormonal. Meningiomas may grow faster during pregnancy.

5. Location…
Most common locations for meningiomas (in descending order) are:
• Parasagittal dura.
•Convexities.
•Sphenoid wing.
•CP angle cistern.
•Olfactory groove.
•Planum sphenoidale.
•90% occur supratentorially.
•1% of meningiomas outside CNS.

6. DIAGNOSTIC TOOLS
MRI
◦ Dural tail, edema
CT SCAN:
◦ Hyperostosis, intratumoral calcifications
ANGIOGRAPHY:
◦ embolization is a consideration
◦ tumor blush

7. CECT…
CT is valuable for the detection of calcification within the tumour, hyperostosis of adjacent bone,
and intraosseous tumour growth, especially in skull-base meningiomas.
 Extra axial mass, well-defined, smooth-contoured, which displaces the normal brain tissue.
Sometimes meningiomas can be multilobulated or calcified.
 Isointense with the normal brain tissue.
Enhance uniformly with I.V contrast. This is more typical of benign meningiomas.
Characteristics suggestive of aggressive behavior are:
 indistinct margins,
 marked edema,
 mushroom-like projections from tumor,
 deep brain parenchymal infiltration
 Heterogenous enhancement

8. CECT…

9. MRI…
MRI is preferred , as it is superior in demonstrating dural origin, as well as vascularity, edema, sinus and
bone invasion.
 Present as solitary round tumours, with close contact to the duramater and strong enhancement with
contrast.
Thickening of the duramater at the perimeter of the tumour (so-called dural tail) is displayed by T1 with
gadolinium.
Isointense or hypointense to gray matter on T1.
Isointense or hyperintense on T2 weighted images.
Areas of necrosis and calcification do not enhance.

11. MRI…

13. OTHER MODALITIES TO COMPLEMENT
DIAGNOSIS
Conventional cerebral angiography:
No routine role in the diagnosis of meningioma, but can be used as
an adjunct to treatment planning in selected cases.(eg. complex
skull base meningioma)
Expression of somatostatin receptor 2 can be used to discriminate
them from healthy tissue, using peptide ligands such as
 ⁶⁸Ga-Dotatate or
 ⁹⁰Y-Dotatoc as PET tracers.

14. TREATMENT OPTIONS
SURGERY
◦ Objective: total removal of the meningioma, dural attachment and bone
involved with the tumor
◦ Priority: preserve and improve neurological function
RADIOTHERAPY
◦ Indications:
◦ Residual tumor left at operation
◦ Recurrence
◦ Tumors could not be treated surgically
◦ Malignant histology

16. OVERVIEW
 Meningiomas: MC intracranial tumours BUT the level of evidence
to provide recommendations for the diagnosis and t/t is low
compared with other tumours such as HGG .
 Meningioma task force of the European Association of Neuro-
Oncology (EANO) assessed the scientific literature and composed a
framework of the best possible evidence-based recommendations
for health professionals.

17. QUESTIONS TO ANSWER
Is intervention needed for incidental meningiomas that have unclear growth
kinetics?
Do all suspected meningioma lesions require histological verification of the
diagnosis?
In cases in which RT is considered, when is the right time and what is the right
fractionation approach?
How will medical therapy develop in the future and what is the role of molecular
profiling?

18. PURPOSE OF REVIEW
Defining standards of care and outlining answers to some
of these questions is the purpose of this Review.

19. LEVEL OF EVIDENCE AND RECOMMENDATION
Class I :Evidence derived from prospective, RCT.
Class II : Evidence derived from prospective studies, including observational studies, cohort
studies, and case-control studies.
Class III :Evidence derived from retrospective studies.
Class IV :Evidence from uncontrolled case series, case reports, and expert opinions.
Recommendation A- requires one or more class I studies or two consistent class II studies,
Recommendation B-requires one or more class II studies or overwhelming class III evidence,
Recommendation C- requires two or more consistent class III studies

20. WHO 2016 CLASSIFICATION

21. MANAGEMENT OUTLINE

22. Simpson Grade of Resection

24. TREATMENT OF MENINGIOMA GRADE 1-
ROLE OF SURGERY
 Asymptomatic: Observation (6 monthly to annually: Clinical examination and MRI )
(evidence level III, Recommendation level C)
 Imaging strongly S/O Meningioma => Histological verification is not mandatory.
However, exclusion of rare differential diagnoses such as metastasis is recommended (Recommendation
level: good practice point)
 Radiologically growth / clinical symptoms: Surgery is the First Choice
(evidence level II, Recommendation level B)
 Extent of resection should be confirmed by a postoperative MRI (within 48 h after
surgery / after 3 months to avoid artefacts)

25. TREATMENT OF MENINGIOMA GRADE 1-
ROLE OF RADIOTHERAPY
Indications:
Elderly patients (older than 65 years)
Not safely accessible by surgery.
Incomplete surgical resection

26. TYPES OF RADIOTHERAPY
SRS-for small tumours
Evidence**: 35 retrospective studies showed a 5-year progression-free survival of 86−100%
after primary stereotactic radiosurgery.
Fractionated EBRT: 50−55 Gy given in doses of 1·8−2·0 Gy per fraction can be
applied (Evidence level III, Recommendation level B).
**Rogers L, Barani I, Chamberlain M, et al. Meningiomas: knowledge base, treatment outcomes, and uncertainties.
A RANO; review. J Neurosurg 2015; 122: 4–23.

27. TYPES OF RADIOTHERAPY
Radiotherapy with subtotal resection: is associated with disease control and
survival rates similar to those reported for gross total resection
IMRT/ fSRT: to spare critical neurovascular structures surrounding the tumour
and to reduce the risk of long-term cognitive deterioration => similar disease
control to conventional radiotherapy.

28. MENINGIOMA GRADE 2.
No clear radiological criteria distinguish WHO grade II meningiomas
Exposure to Ionising Radiation: Increased Risk For Meningioma.
Radiation-associated meningiomas: More likely to be atypical or malignant and multifocal than
sporadic
TERT mutations are associated with higher grade meningioma grades
INCREASED RISK OF RECURRENCE THAN GRADE I

29. TREATMENT OF MENINGIOMA GRADE 2
ROLE OF SURGERY
 Surgery is the first choice of treatment.
 Should aim to achieve Simpson Grade I resection
 (Evidence level III, recommendation level B)

30. FOLLOW UP
After Total resection:
 Annual MRI for 5 years => Biannual follow-ups.
After subtotal resection:
 MRI follow up at 6 and 12 months followed by annually.

31. TREATMENT OF MENINGIOMA GRADE 2-
ROLE OF RADIOTHERAPY
Role of adjuvant radiotherapy after gross complete resection?????
◦ ROAM/EORTC 1308 trial (ISRCTN71502099) : whether radiotherapy reduces the risk of or
delays tumour recurrence.
 Newly diagnosed Atypical Meningioma (WHO grade II)
 Gross total resection (Simpson grade I–III)
 early adjuvant radiotherapy (60 Gy in 30 fractions) vs. observation

32. TREATMENT OF MENINGIOMA GRADE 2-
ROLE OF RADIOTHERAPY
Role of adjuvant radiotherapy after partial resection??
 Adjuvant radiotherapy (54–60 Gy given in 1·8−2·0 Gy per fraction) should
be considered (evidence level III, recommendation level C)
Fractionated RT is preferred over SRS techniques
although SRS offers similar results for small tumours/ tumour residual

33. TREATMENT OF MENINGIOMA GRADE 2-
ROLE OF CHEMOTHERAPY AND TARGETED THERAPY
Retrospective studies and small prospective studies: (WHO grade II and III
meningiomas)
o Hydroxycarbamide
o Cyclophosphamide/Doxorubicin/Vincristine chemotherapy,
o interferon-alfa,
o Megestrol acetate, Medroxyprogesterone acetate, Octreotide, Pasireotide (long-acting release),
o Imatinib, Erlotinib, Gefitinib, Vatalanib, Sunitinib,
o Bevacizumab.
Most promising results for Bevacizumab, Vatalanib, and Sunitinib
EORTC phase 2 trial (NCT02234050): efficacy of TRABECTEDIN shown promising activity in
recurrent WHO grade II and grade III meningiomas.

34. FOLLOW UP
MRI : every 6 months for 5 years then annually

35.  Anaplastic meningioma:
irregular shape
higher relative cerebral blood volume (rCBV)
Recurrence risk is high
Can metastasize systemically.
Contain a high proportion of NF2 mutations , diffuse growth and invasion of
the cortex.
MENINGIOMA GRADE 3 vs GRADE 1 & 2

36. TREATMENT OF MENINGIOMA GRADE 3
 Surgical resection:
o should be as radical as possible
(evidence level III, recommendation level C).
 Adjuvant Radiotherapy: Fractionated
o Dose: at least 54 Gy 1·8−2·0 Gy fractions
(evidence level III, recommendation level B)
Dose:
 Complete resection: 54 Gy
 Incomplete resection: 6o Gy.
Pharmacotherapy options remain experimental; (evidence level IV, recommendation
level C)

37. ONGOING TRIALS
RTOG 0539 trial (NCT00895622):
WHO Grade II: RT with 54 Gy in 30 fractions after gross total resection
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.
EORTC 22042-26042 trial (NCT00626730):
WHO Grade II and III after Gross Total resection: 60 Gy in 30 fractions
After subtotal resection: 60 Gy in 30 fractions followed by Boost 10 Gy in 5 fractions to residual
- Results awaited

38. FOLLOW UP
MRI follow up every 6 months
(every 3 months in rapidly growing cases)

39. SPINAL MENINGIOMA
Surgical resection: 1st Choice
to remove the tumour and decompress the spinal cord is the therapy of choice
If surgical resection not possible: SRS or hypofractionated RT
(recommendation level: good practice point)
Adjuvant therapy is done according to WHO grade and resection.

40. RECOMMENDATIONS-TAKE HOME
MESSAGE-DIAGNOSIS
Radiological diagnosis of meningioma should be made by MRI
Conventional angiography should be restricted to selected cases
Tissue for future molecular analysis should be stored if available
Histological verification of meningioma is not mandatory in all cases

41. RECOMMENDATIONS-TAKE HOME
MESSAGE-TREATMENT
Asymptomatic patients can be managed by observation only
If t/t is indicated in meningioma of any WHO grade, Surgery is the first option
Complete removal (Simpson grade I) is the primary goal of surgery
Extent of resection should be confirmed by MRI
Embolisation should be restricted to selected cases
Radiosurgery might be the first option in small WHO Grade I meningiomas in
specific locations

42. RECOMMENDATIONS-TAKE HOME
MESSAGE-TREATMENT…..
WHO Grade I meningioma who cannot undergo surgery : SRS or FSRT
Subtotal resection in WHO Grade I: SRS or FSRT allows comprehensive tumor t/t
while reducing the risk of adverse effects.
WHO Grade II – Subtotal resection: should receive RT.
Pharmacotherapy is experimental in any grade of meningioma and should only be
considered if no further surgical or radiotherapy options exists.

43. RECOMMENDATIONS-TAKE HOME
MESSAGE-FOLLOW UP
WHO grade I:
 First 5 years: Annually
 After 5 years: every 2 years.
WHO grade II :
 First 5 years: Every 6 months
 After annually after 5 years
WHO grade III :
 Every 3–6 months indefinitely

44. FUTURE DIRECTIONS
Promising progress in diagnosis and t/t of meningiomas.
The new WHO classification of meningioma.
 Diagnosis of the extension of complex meningioma:
eg, pre-treated intraosseous skull-base tumours - remains challenging.
New PET tracers binding to somatostatin receptor 2 is a promising technique:
Role in delineation, therapy planning & response assessment.

45. Last few words of Hope….
Surgical techniques and approaches: more refined in terms of individualised risk
assessment.
Skull-base meningiomas: Subtotal resection and SRS may be used more frequently
to minimise treatment risk.
Multidisciplinary diagnosis and therapy of meningiomas planned in dedicated
brain tumour boards should become standard of care
Prospective studies assessing efficacy and safety of novel systemic therapies are
on their way.
These studies will help to generate higher levels of evidence for future treatment concepts and
hopefully improve outcomes for the minority of tumours that are still difficult to control.