Management of Meningioma
3/25/2023 1
DR KANHU CHARAN PATRO
MD,DNB(Radiation Oncology),MBA,FICRO,FAROI(USA),PDCR,CEPC
HOD,RADIATION ONCOLOGY
Mahatma Gandhi Cancer Hospital And Research Institute, Visakhapatnam
drkcpatro@gmail.com /M- +91-9160470564

HANDLING MOTHER-IN-LAW

THE MOTHER OF YOUR SPOUSE

Be compassionate, not ruthless or angry
Give motherly love

MY GRADE ll PATIENT IS DOING
WELL FOR LONG TIME
MY GRADE I PATIENT IS NOT
DOING WELL
9

Iske Piche Bhi
ModiJi hai
Are baba, Iske
Piche molecular
profile hai
10

Changes in meningioma classification- WHO 5th edition
1. Meningioma is considered a single type in WHO CNS5, with its broad morphological
spectrum reflected in 15 subtypes.
2. It is now emphasized that the criteria defining atypical or anaplastic (ie, grade 2 and 3)
meningioma should be applied regardless of the underlying subtype.
3. As in prior classifications, chordoid and clear cell meningioma are noted to have a
higher likelihood of recurrence than the average CNS WHO grade 1 meningioma and
have hence been assigned to CNS WHO grade 2;
4. In addition, historically, rhabdoid and papillary morphology qualified for CNS WHO
grade 3 irrespective of any other indications for malignancy. While papillary and
rhabdoid features are often seen in combination with other aggressive features, more
recent studies suggest that the grading of these tumors should not be based on a
rhabdoid cytology or papillary architecture alone.
5. Several molecular biomarkers are also associated with classification and grading of
meningiomas, including SMARCE1 (clear cell subtype),
6. BAP1 (rhabdoid and papillary subtypes), and KLF4/TRAF7 (secretory subtype)
mutations,
11

Do you know?
From 2004 to 2010 WHO grade 2 atypical intracranial meningiomas increased
from 0.28 (95% confidence interval [CI]: 0.27-0.29) to 0.30 (95% CI: 0.28-0.32),
representing an annual percentage change of 3.6% (95% CI: 0.8%-6.5%).
Conversely, from 2000 to 2010, the incidence of WHO grade 3 anaplastic
meningiomas decreased from 0.13 (95% CI: 0.11-0.14) to 0.06 (95% CI: 0.06-0.07),
representing an annual percentage change of −5.4% (95% CI: −6.8% to −4.0%).
From 2004 to 2010, the overall proportion of WHO grades 1, 2, and 3 intracranial
meningiomas (based on the WHO classification from 2000) was 94.6%, 4.2%, and
1.2%, respectively.
Meningiomas of WHO grades 1 and 2 overall are 2.3 times more common in
females compared to males

Molecular aggressiveness
• Likewise, any meningioma with TERT
promoter mutation and/or CDKN2A/B
homozygous deletion is allotted to WHO grade
3, irrespective of histological criteria of
anaplasia.

Cause
Prior irradiation
Atom bomb exposures
Exogenous hormones
The most frequent alterations in all WHO grades
are chromosome 22q deletions and mutation of
the other NF2 allele.

WHO Grade l meningioma
• Treatment of WHO grade 1 meningiomas should be stratified by the major prognostic
factors and clinical constellations summarized above.
• In case of incidentally diagnosed and asymptomatic tumors observation by annual MRI
initially is the management strategy of choice (evidence level III, recommendation level C).
• Beyond routine neurological investigation, special attention should be directed to cognitive
impairment because its presence argues in favor of intervention.
• Therapy is indicated in symptomatic or growing meningiomas with surgery being the
first option for the following reasons: the patient can often be cured by Simpson grade I
resection, neurological and cognitive symptoms and signs may be reversed, tissue-based
diagnosis can be made, tissue is gained for molecular pathologic testing.
• Tissue should be stored for the option of future targeted therapies (good practice point).
• Conversely, possible short- and long-term effects of surgery on cognition and HRQoL
should be considered.
• Radiosurgery may be an alternative in patients with relative or absolute
contraindications for surgery and with small tumors without mass effect, although a higher-
grade meningioma or a different histology cannot be entirely ruled out.
• It offers long-term local control in the range of 90% after 10 years.
• Moreover, radiosurgery can be used in a combination approach consisting of subtotal
resection of large skull base meningiomas with a high surgical risk profile and
consecutive radiosurgery may be considered

WHO Grade ll meningioma
• If a radiologically assumed meningioma shows rapid growth during observation, a
higher-grade meningioma (or metastasis in particular cases) must be suspected. In
meningioma WHO grade 2, therapy is mandatory.
• To gain tissue for the diagnosis and remove mass effect, surgery is the first option.
• Resection according to Simpson grade I should be achieved.
• Because of increased risk for recurrence, the follow-up interval should be 6 months for 5
years; thereafter, 1-year intervals are recommended.
• There are increasing data on fractionated RT in WHO grade 2 meningiomas.
• However, no randomized trials have been completed, allowing only level IV evidence
regarding the question whether WHO grade 2 meningiomas should be irradiated after
resection Simpson I-III.
• For WHO grade 2 meningioma with a Simpson IV-V resection, RT is recommended.
• There is no established pharmacotherapy for these tumors.

WHO Grade lll meningioma
• These tumors are characterized by rapid growth, early
recurrence, risk of systemic metastasis, and molecular features on
genetic and epigenetic levels.
• Radical surgery as feasible is recommended, followed by
fractionated RT.
• No role for pharmacotherapy has been defined.

Spinal meningioma
1. Large tumor size and “borderline” or “malignant”
histology were associated with increased use of RT.
2. There appeared to be no association with OS, but RT
was associated with a reduction of mortality in the
subset of borderline and “malignant” tumors.
Surgical resection is the therapy of choice for patients
with spinal meningiomas.
Resection should be according to Simpson grade I or II
to decompress the spinal cord and remove the tumor.
Gross total resection should also be attempted in
elderly patients.
There are little data about RT in spinal meningiomas.

Ongoing studies
RTOG 0539 trial
(NCT00895622)
EORTC 22042-26042 trial
(NCT00626730)
ROAM/EORTC 1308 trial
(ISRCTN71502099)

Workflow
without
radiomics
Gu et al./frontiers in oncology/2020

Radiomics of meningioma grade l

Radiomics of meningioma grade l

Radiomics of meningioma grade ll

Radiomics of meningioma garde lll

The magnetic resonance images [postcontrast T1-weighted (T1C)] of a
patient with (A) WHO I meningioma, (B) WHO II meningioma, and (C) WHO

Workflow
with
radiomics
Gu et al./frontiers in oncology/2020

Molecular alteration decides the
behavior of tumor not the histopathology
30

Definition-MOLECULAR PROFILING
• Molecular profiling—or “tumor genomic profiling”—is a form of
testing that classifies tumors based on this genetic make-up
to help diagnose and treat cancer.
• Molecular testing, such as molecular profiling of brain
tumors, improves diagnostic accuracy, allows for predictive
prognosis, and enables target identification.
• At present, targeted therapy has become one of the most
promising treatment options for many tumors
31

Brain tumor diagnosis
Next generation
sequence
[NGS]
Methylation profiling
Immunohistochemistry
[IHC]
Microscopic
Histology
32

Histology

• Immunohistochemistry (IHC) is an important application of monoclonal as well as polyclonal
antibodies to determine the tissue distribution of an antigen of interest in health and disease.
IHC is widely used for diagnosis of cancers; specific tumor antigens are expressed de novo or
up-regulated in certain cancers.
34

The basic next-generation sequencing process involves fragmenting
DNA/RNA into multiple pieces, adding adapters, sequencing the libraries,
and reassembling them to form a genomic sequence.
35

Methylation analysis is the study of chromosomal patterns of DNA or
histone modification by methyl groups.
36

Look A like
37

Surrogate
immunohistochemistry
38

Aggressiveness
LOCATION GRADE MOLECULAR
PROFILE
SIMPSON
GRADING

Surgery principle - Simpson grade

SIMON
GRITSCH/CANCER/2022

Grading
by
location
and
molecular
MAY AI RASHED/FRONIERS IN ONCOLOGY/2022

Molecular profile

LOCATION-MOLECULAR

Defining grade ll meningioma
• 4–19 mitoses per 10 hpf;
• At least 3 Three of the following 5 atypical features:
• Spontaneous necrosis,
• Macronucleoli,
• Loss of architecture (sheeting),
• Hypercellularity
• Small cell change
• Brain invasion
• Predominant (> 50% of the tumor volume) clear-cell or chordoid
morphology.
Defined as meningiomas with ll

Stephanie M. Robert/JOURNAL OF NEUROONCOLGY/2022

Options
Observation
Surgery
Surgery + RT
RT alone
SRS
Fractionated SRS
Conventional

Key points

Management algorithm

MENINGIOMA Mx
PHILIPP EUSKIRCHEN/NEUROONCOLOGY/2018

NCCN GUIDELINES - 2022

Retrospective studies for GRADE ll after GTR
Sam Q. Sun/NEUROSURGICAL FOCUS/2015

Retrospective studies for GRADE ll after STR
Sam Q. Sun/NEUROSURGICAL FOCUS/2015

What should I look for in brain?
OS
Overall Survival
PFS
Progression
Free Survival

Grade ll
meningioma
Sam Q. Sun/NEUROSURGICAL FOCUS/2015

Statistical analysis of prognostic factors affecting PFS and OS
Jae Ho Lee/J Korean Neurosurg/2017

PET CT and MRI

RTOG-0539

Initial outcomes of low risk

OUTCOME LOW RISK
3y 5y 10y
TOTAL
PFS 91.4% 91.4% 85.0%
OS 98.3% 98.3% 93.8%
GTR
PFS 94.3% 94.3% 87.6%
OS 97.1%. 97.1%. 90.4%.
STR
PFS 83.1% 72.7% 72.7%
OS 100% 100% 100%
C Leland Rogers/NEUROONCO/2023

Conclusion low risk

Intermediate risk
initial outcome

PFS

OS

Failure

Toxicity

Conclusion
C Leland Rogers/J Neurosurg./2018

High risk initial outcome

PFS

OS

Progression

PFS
SUBGROUP

Conclusion high risk
C Leland Rogers/IJROBP/2020

Aggressiveness on MRI
Although in general, the presence of severe adjacent oedema is considered more compatible with
aggressive meningiomas, in some histologically benign types such as secretory type, oedema can be
disproportionately larger than the small tumour size.

EORTC
22042-26042
At a median follow up of 5.1 years, the
estimated 3-year PFS is 88.7%, hence
significantly greater than 70%. Eight (14.3%)
treatment failures were observed. The 3-year
overall survival was 98.2%. The rate of late
signs and symptoms grade 3 or more was
14.3%.

EORTC
22042-26042
At a median follow up of 5.1 years, the estimated 3-year PFS is 88.7%, hence significantly greater
than 70%. Eight (14.3%) treatment failures were observed. The 3-year overall survival was
98.2%. The rate of late signs and symptoms grade 3 or more was 14.3%.

ROAM
TRIAL
The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical
resection of Atypical Meningioma

POOLED ANALYSIS

Grade lll
Meningioma
Sam Q. Sun/NEUROSURGICAL FOCUS/2015

Targeted
agents in
meningioma
MAY AI RASHED/FRONIERS IN ONCOLOGY/2022

FOLLOW UP
• First 5 years: Annually
• After 5 years: every 2 years.
WHO grade I:
• First 5 years: Every 6 months
• Then annually after 5 years
WHO grade II :
• Every 3–6 months indefinitely
WHO grade III :

Conclusion
Complete removal (Simpson grade I) is the primary goal of surgery
Radiosurgery might be the first option in small WHO Grade I
meningiomas in specific locations
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.
Prospective studies assessing efficacy and safety of novel systemic
therapies are on their way.

SUMMARY

CELEBRATE MOTHER-IN-LAW