RESEARCH—HUMAN—CLINICAL STUDIES

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Necrosis and Brain Invasion Predict
Radio-Resistance and Tumor Recurrence in Atypical
Meningioma: A Retrospective Cohort Study
Monica Emili Garcia-Segura, BACKGROUND: Meningiomas are the most common tumors occurring in the central
HBSc∗ nervous system, with variable recurrence rates depending on World Health Organization
Anders Wilder Erickson, BS‡ grading. Atypical (Grade II) meningioma has a higher rate of recurrence than benign (Grade
Rishi Jairath, MD∗
I) meningioma. The efficacy of adjuvant radiotherapy (RT) to improve tumor control has
been questioned.
David G. Munoz, MD‡ §
OBJECTIVE: To investigate clinical and histopathological predictors of tumor recurrence
∗‡¶
Sunit Das, MD, PhD and radio-resistance in atypical meningiomas.
∗
Division of Neurosurgery, University of
METHODS: This cohort study retrospectively reviewed all patients in St. Michael’s Hospital
Toronto, Toronto, Canada; ‡ Institute of CNS tumor patient database who underwent surgical resection of a Grade II menin-
Medical Science, University of Toronto, gioma from 1995 to 2015. Cases with neurofibromatosis type II, multiple satellite tumors,
Toronto, Canada; § Department of
Laboratory Medicine and Pathobiology,
spinal cord meningioma, radiation-induced meningioma, and perioperative death were
St. Michael’s Hospital, University of excluded. Patient demographics, neuropathological diagnosis, tumor location, extent of
Toronto, Toronto, Canada; ¶ Li Ka Shing resection, radiation therapy, and time to recurrence or progression were recorded. Cox
Knowledge Institute, St. Michael’s
Hospital, University of Toronto, Toronto,
univariate regression and Kaplan-Meier survival analysis were employed to identify risk
Canada factors for recurrence and radio-resistance.
RESULTS: Among 181 patients, the combination of necrosis and brain invasion was
Correspondence: associated with an increased recurrence risk (hazard ratio [HR] = 4.560, P = .001) and the
Sunit Das, MD, PhD,
Division of Neurosurgery,
lowest progression-free survival (PFS) relative to other pathological predictors. This trend
University of Toronto, was maintained after gross total resection (GTR, P = .001). RT was associated with decreased
30 Bond St, PFS (P = .001), even in patients who received GTR (P = .001).
Toronto M5B 1W8, Canada.
Email: sunit.das@utoronto.ca
CONCLUSION: The combination of necrosis and brain invasion is a strong predictor of
tumor recurrence and radio-resistance in meningioma, regardless of EOR or adjuvant RT.
Received, April 9, 2020. Our findings question the sensibility of brain invasion as an absolute criterion for Grade II
Accepted, June 8, 2020. status.
Copyright 
C 2020 by the KEY WORDS: Atypical meningioma, Brain invasion, Necrosis, Radiation, Recurrence, Surgery
Congress of Neurological Surgeons
Neurosurgery 0:1–7, 2020 DOI:10.1093/neuros/nyaa348 www.neurosurgery-online.com

M
eningiomas are the most common
primary tumor of the central nervous
system (CNS), accounting for almost
37% of all reported CNS tumors in adults.1
ABBREVIATIONS: AM, atypical meningioma; CI,
confidence interval; CNS, central nervous system;
EOR, extent of resection; GTR, gross total resection;
HR, hazard ratio; OR, odds ratio; PFS, progression-
free survival; RT, radiotherapy; STR, subtotal
resection; WHO, World Health Organization
Supplemental digital content is available for this article at
www.neurosurgery-online.com.
Atypical meningiomas (AMs, Grade II) are
associated with a significantly higher risk of
tumor recurrence than benign meningiomas.2,3
In addition to extent of resection (EOR),4
certain histological features appear to be critical
as indicators of prognosis. For example, intratu-
moral necrosis has been shown to be a strong
predictor of tumor progression after subtotal
resection (STR).5,6 Brain invasion has also been
associated with tumor recurrence in combination
with high mitotic index.7
In this retrospective study, we reviewed all
consecutive patients at a single institution who
underwent surgical resection of a World Health
Organization (WHO) Grade II meningioma

NEUROSURGERY VOLUME 0 | NUMBER 0 | 2020 | 1

GARCIA-SEGURA ET AL
from 1995 to 2015. We found the combination of necrosis and
brain invasion to be a strong predictor of tumor recurrence and
radio-resistance, regardless of resection type.
METHODS
Patient Selection
Patients were identified for study through review of the St. Michael’s
Hospital CNS tumor patient database following study approval by the
hospital Research Ethics Board, who waived the need for consent, as
this study was conducted through blinded chart review. A total of
181 cases assigned the histological diagnosis of WHO Grade II
meningioma between years 1995 and 2015 were identified. Secondary
neuropathological review of all cases was performed by a board-certified
neuropathologist to confirm diagnosis, grade, and additional patho-
logical characteristics (DM).8 Patients with neurofibromatosis type
II, multiple satellite tumors, spinal cord meningioma, or radiation-
induced meningioma were excluded. Patients treated with preoper-
ative embolization were excluded to ensure that investigation only
captured cases with spontaneous necrosis. EOR was defined using
the Simpson9 Grading System in accordance with postoperative
notes and imaging follow-up (magnetic resonance imaging, computed
tomography). Patients who underwent Simpson9 Grade I or II
tumor resection were categorized as gross total resection (GTR),
whereas patients with Grade III or IV resection were categorized
as STR.
Patients with postoperative follow-up less than 4 yr were excluded,
as were 7 patients who died in the perioperative period. Patients
who underwent preoperative embolization were also excluded, given its
confounding effects on tumor histopathology.5
Clinicopathological Variables
Tumor location was defined according to the following: convexity,
parafalcine/parasagittal, anterior skull base (including olfactory groove,
tuberculum sella, and planum sphenoidale), middle skull base (including
sphenoid wing, cavernous sinus, and spheno-orbital), or posterior skull
base (petroclival and infratentorial).
Pathological features included bone invasion, brain invasion, and
brain and bone invasion. Clear cell subtype, rhabdoid subtype, and
choroid meningioma subtype were categorized as AM variant. High
mitotic count was defined as ≥4 × 10 high power field.
Adjuvant radiotherapy (RT) was defined as postoperative stereo-
tactic radiosurgery or external beam radiation therapy, prior to tumor
recurrence. Tumor recurrence was defined as interval increase in tumor
size or identification of lesion regrowth on follow-up imaging or
follow-up notes. Tumor progression was defined as the same for
patients with STR. Progression-free survival (PFS) was defined as the
number of months from surgical resection until tumor recurrence or
progression.
Statistical Tests
Statistical analysis was performed using SPSS 23.0 (IBM, Armonk,
New York). The χ 2 test was used to assess differences in pathology-
and treatment-related predictors in our entire cohort, as well as in
further stratifications. Upon meeting the underlying assumptions of the
model, we performed a Cox univariate regression analysis to identify
pathology- and treatment-related risk factors for AM recurrence in our
2 | VOLUME 0 | NUMBER 0 | 2020
entire cohort. Kaplan-Meier survival analysis was performed in the R
programming language (v3.6.1. R Foundation for Statistical Computing,
Vienna, Austria) using the package survival (v3.1-12; Therneau, T.M.).
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All Kaplan-Meier survival curves were reported with a P value obtained
from log-rank test. Unadjusted logistic regression models were used to
assess the relationship between adjuvant RT and several clinicopatho-
logical variables. These results were reported as odds ratio (OR) with
associated 95% CIs, as well as P value. All statistical analyses were
conducted using an α = 0.05 significance.
RESULTS
Participants
We identified 181 patients with a confirmed diagnosis of AM
who met inclusion criteria (Table 1). Out of 181 cases, 70 cases
had documented radiographic evidence of meningioma recur-
rence (38.7%), whereas 111 cases out of 181 did not (61.3%).
In cases with radiographic evidence of recurrence, mean time to
recurrence was 46.5 mo (SD ± 36.8).
Pathological and Treatment-Based Predictors of Tumor
Recurrence
Using Cox univariate regression analysis, we first analyzed
the likelihood of pathological and treatment-related factors as
putative predictors of tumor recurrence (Table 2). Male gender
(hazard ratio [HR] 1.796, P = .014), combined necrosis and brain
invasion (HR 4.560, P = .001), STR (HR 2.729, P = .001),
and adjuvant RT (HR 4.352, P = .001) were associated with
tumor recurrence, whereas tumor location was not (P = .320).
The association between necrosis alone and increased risk of
tumor recurrence did not reach statistical significance (HR 1.898,
P = .145).
Kaplan-Meier analysis confirmed the previously described
trends, with decreased PFS in cases with combined necrosis
and brain invasion relative to any other pathological predictor,
including necrosis alone (P = .001 with log-rank test; Figure 1A).
Brain invasion alone was the pathological predictor with the
longest PFS (Figure 1A). Kaplan-Meier also showed a decreased
PFS in patients who underwent STR compared to GTR
(P = .001 with log-rank test; Figure 1B), as did patients who
underwent adjuvant RT compared to those that had no history
of RT (P = .001 with log-rank test; Figure 1C).
Pathological and Treatment-Based Predictors of
Received Adjuvant RT
Given these surprising results, we then asked which clini-
copathological factors were associated with the administration
of adjuvant RT in our cohort (Table, Supplemental Digital
Content 1). Using a logistic regression analysis, combined
necrosis and brain invasion was the only pathological feature
significantly associated with administered RT (OR = 3.088,
P = .034). STR was also significantly associated with adminis-
tered RT (P = .001). Neither tumor location nor patient gender
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 RESISTANCE AND RECURRENCE IN ATYPICAL MENINGIOMA

TABLE 1. Study Population and Hazard Ratios of Treatment-Related Predictors of Tumor Recurrence Using Univariate Cox Regression Analysis

Characteristic N (%) Mean (±SD) Univariate hazard ratio (95% CI) P value

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Population 181
Age at surgery – 59.6 mo (±14.3) 1.019 (1.001-1.038) .038
Gender
Female 109 (60.2) – Indicator .014
Male 72 (39.8) – 1.796 (1.124-2.871)
Tumor location
Convexity 68 (37.6) – Indicator
Falcine/parasagittal/superior tentorial 48 (26.5) – 1.369 (0.782-2.398) .272
Anterior skull base 27 (14.9) – 0.684 (0.296-1.581) .374
Middle skull base 26 (14.4) – 1.046 (0.502-2.178) .904
Posterior skull base 12 (6.6) – 0.859 (0.299-2.469) .778
Extent of resection
GTR 126 (69.6) – Indicator
→ With RT 33 (26.2) – –
STR 55 (30.4) – 2.729 (1.705-4.368) .001
→ With RT 29 (52.7) – –
Pathology
High mitotic count 28 (15.5) – Indicator
Necrosis 48 (26.5) – 1.898 (0.802-4.489) .145
Brain invasion 48 (26.5) – 0.560 (0.196-1.596) .278
Necrosis and brain invasion 38 (21.0) – 4.560 (1.992-10.440) .001
AM variant 19 (10.5) – 1.631 (0.572-4.652) .360
Adjuvant radiotherapy (RT)
No 119 (65.7) – Indicator
Yes 62 (34.3) – 4.352 (2.678-7.073) .001
Tumor recurrence
Yes 70 (38.7) 46.5 mo (±36.8) – –
No 111 (61.3) – –

predicted administration of RT (Table, Supplemental Digital
Content 1).
GTR-Specific Pathological and Treatment-Based
Predictors of Meningioma Recurrence
We then investigated whether previously reported predictors of
meningioma recurrence may act differently depending on EOR.
Of the 126 cases in the GTR group, 36 had tumor recurrence,
with a PFS of 44.6 mo (SD ± 32.0). Pathology subtype and
RT were significantly associated with tumor recurrence in this
group (Table 2). Nearly half of all cases with reported tumor
recurrence presented combined necrosis and brain invasion on
histopathology (HR = 4.377, P = .008). Necrosis alone was
seen in a smaller subgroup of patients with GTR (25%) and
showed a nonsignificant trend toward increased risk of recurrence
(HR = 1.344, P = .623). Combined necrosis and brain invasion
on histopathology was the pathological predictor with the lowest
associated PFS (P = .001 with log-rank test; Figure 2A). Brain
invasion alone was again the pathological predictor with the
highest PFS (Figure 2A). RT significantly predicted a decreased
PFS in the GTR group (HR = 0.001, P = .001, Figure 2B).
PFS was comparable between patients who received RT (44.0
mo; SD ± 30.7) and patients who did not receive RT (45.4 mo;
SD ± 35.0).
STR-Specific Pathological and Treatment-Based
Predictors of Meningioma Progression
Of the 55 cases in the STR group; 34 had tumor progression,
with an PFS of 48.5 mo (SD ± 41.7). Pathological subtype,
but not RT, was significantly related to tumor progression
(P = .002 and P = .088, respectively; Table 2). Although
not significant (P = .655), 47.6% of all cases without tumor
progression demonstrated brain invasion (HR = 0.711), whereas
the majority of cases in which tumor progression was noted
demonstrated combined necrosis and brain invasion or necrosis
alone (HR = 4.953, P = .013; and HR = 3.740, P = .044,
respectively).
As in cases with GTR, necrosis with brain invasion and necrosis
alone was a strong predictor of decreased PFS after STR (P = .001
with log-rank test; Figure 3A). Brain invasion was again the
pathological predictor associated with the highest PFS. Regarding
adjuvant RT, time to progression differed slightly based on RT

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GARCIA-SEGURA ET AL

TABLE 2. GTR and STR-Subcohort Populations and Hazard Ratios of Treatment-Related Predictors of Tumor Recurrence Using Univariate Cox
Regression Analysis

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Patients with Univariate hazard Patients without
GTR subcohort recurrence N (%) Mean (±SD) ratio (95% CI) P value recurrence N (%)

Time until recurrence 36 44.6 mo (SD ± 32.0) 90

Pathology
High mitotic count 4 (11.1) Indicator 16 (17.8)
Necrosis 9 (25) 1.344 (0.414-4.365) .623 26 (28.9)
Brain invasion 3 (8.3) – 0.429 (0.096-1.916) .268 31 (34.4)
Necrosis and brain invasion 16 (44.4) – 4.377 (1.460-13.120) .008 8 (8.9)
AM variant 4 (11.1) 1.670 (0.418-6.678) .468 9 (10)
Adjuvant radiotherapy (RT) –
No 14. (38.9) 45.4 mo (SD ± 35.0) Indicator 79 (87.8)
Yes 22 (61.1) 44.0 mo (SD ± 30.7) 6.328 (3.219-12.443) .001 11 (12.2)
Patients with Univariate hazard Patients without
STR subcohort progression N (%) Mean (±SD) ratio (95% CI) P value progression N (%)
Time until progression 34 48.5 mo (SD ± 41.7) 21
Pathology
High mitotic count 3 (8.8) Indicator 5 (23.8)
Necrosis 11 (32.4) – 3.740 (1.034-13.525) .044 2 (9.5)
Brain invasion 4 (11.8) 0.711 (0.159-3.176) .655 10 (47.6)
Necrosis and brain invasion 13 (38.2) – 4.953 (1.395-17.584) .013 1 (4.8)
AM variant 3 (8.8) – 1.572 (0.317-7.799) .580 3 (14.3)
Adjuvant radiotherapy (RT)
No 13 (38.2) 54.5 mo (SD ± 56.1) Indicator 13 (61.9)
Yes 21 (61.8) 44.8 mo (SD ± 30.8) 1.793 (0.895-3.593) .099 8 (38.1)

administration: 44.8 mo (SD ± 30.8) among cases treated with
RT, compared to 54.5 mo (SD ± 56.1) for cases that did not
receive RT (Table 2). Cox regression and Kaplan-Meier analysis
predicted a nonsignificant decrease in PFS in patients in the STR
group who received RT, compared to those with no history of RT
(HR = 1.793, P = .099, P = .093 with log-rank test; Figure 3B).
Necrosis and Brain Invasion Predicts Tumor Recurrence
Regardless of Resection Type and RT in Atypical
Meningioma
With these findings, we next asked if combined necrosis and
brain invasion is a specific predictor of AM recurrence, regardless
of EOR or adjuvant RT. We analyzed the effect of combined
necrosis and brain invasion on tumor recurrence and PFS, as well
as the effects of high mitotic count and each of necrosis and brain
invasion individually.
High mitotic count had no predictive effect on tumor recur-
rence, regardless of resection type (P = .360 with log-rank
test; Figure, Supplemental Digital Content 2A). Necrosis alone
was significantly associated with decreased PFS in cases that
underwent STR (P = .001 with log-rank test; Figure, Supple-
mental Digital Content 2B). Interestingly, combined necrosis
and brain invasion predicted a significantly lower PFS in both
GTR and STR subgroups (P = .031 with log-rank test; Figure,
Supplemental Digital Content 2C). Among patients with brain
invasion alone, STR did not predict recurrence (P = .103 with
log-rank test; Figure, Supplemental Digital Content 2D).
In terms of the relationship between tumor recurrence and
RT, high mitotic count did not predict recurrence, regardless of
RT status (P = .92 with log-rank test; Figure, Supplemental
Digital Content 3A). In all patients presenting necrosis alone
on histopathology, RT was associated with a decreased PFS,
compared to those with no history of RT (P = .002 with log-rank
test; Figure, Supplemental Digital Content 3B). Combined
necrosis and brain invasion predicted a significantly lower PFS,
regardless of RT status (P = .001 with log-rank test; Figure,
Supplemental Digital Content 3C). In fact, in our patient
cohort, tumor recurrence was universal in patients with evidence
of combined necrosis and brain invasion on histopathology,
regardless of administration of adjuvant RT (Figure, Supple-
mental Digital Content 3C). Among patients with brain
invasion alone, RT did not predict recurrence (P = .129 with
log-rank test; Figure, Supplemental Digital Content 3D).
DISCUSSION
In this retrospective study, we investigated clinicopathological
predictors of tumor recurrence in patients that underwent surgical
resection of AM (WHO Grade II), as well the potential beneficial
effect of adjuvant RT on prognosis.

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 RESISTANCE AND RECURRENCE IN ATYPICAL MENINGIOMA

A B Surgery + Gross total resection + Subtotal resection

Pathology + High mitotic count + Necrosis + Brain invasion + AM variant + Necrosis and brain invasion
1.00

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1.00

+
0.75
0.75 + +

Survival probability
Survival probability

+
+
0.50
0.50

0.25 0.25
+
p < 0.0001 p < 0.0001

0.00 0.00
0 50 100 150 200 250 0 50 100 150 200 250
Months until recurrence Months until recurrence
Number at risk Number at risk

Surgery
Pathology

High mitotic count 28 24 22 21 21 0

Necrosis 48 32 30 28 28 0 Gross total resection 55 32 24 22 22 0
Brain invasion 48 43 41 41 41 0 Subtotal resection 126 100 94 90 90 0
AM variant 19 14 12 12 12 0
Necrosis and brain invasion 38 19 13 10 10 0 0 50 100 150 200 250
0 50 100 150 200 250 Months until recurrence
Months until recurrence

Radiotherapy (RT) + No RT + Adjuvant RT

C 1.00

+
0.75
Survival probability

0.50

+
0.25
p < 0.0001

0.00

0 50 100 150 200 250

Months until recurrence
Radiotherapy (RT)

Number at risk
No RT 119 99 96 93 93 0
Adjuvant RT 62 33 22 19 19 0
0 50 100 150 200 250
Months until recurrence

FIGURE 1. Progression-free survival in patients with atypical meningioma. Kaplan-Meier analysis of our total study population, stratified by A, pathological predictors
(P = .001 with log-rank test), B, extent of resection (EOR)(P = .001 with log-rank test), and C, adjuvant radiotherapy (RT) status (P = .001 with log-rank test).

We found STR to be a significant predictor of tumor recurrence There is also mixed evidence regarding the beneficial effect
compared to GTR. The literature widely recognizes the role that of adjuvant RT in deterring AM recurrence after STR. Several
EOR plays in determining AM prognosis.10,11 studies have reported evidence supporting a benefit with adjuvant
Adjuvant RT was associated with higher risk of tumor recur- RT on overall survival,14,15 recurrence rates, and PFS.16,17
rence in patients with AM. Upon stratification by EOR, this Conversely, other studies have argued against the use of adjuvant
finding remained statistically significant in GTR cases only; in our RT in STR, showing no significant differences in outcome
STR subcohort, the trend of RT with shorter PFS was nonsignif- when compared to STR alone.18,19 In our cohort, adjuvant RT
icant. Multiple other studies have identified a negative associ- was associated with worse PFS regardless of EOR. Although
ation of adjuvant RT with disease control and survival in patients these results might seem paradoxical, similar findings have been
with AM,6,12 compared to GTR alone. In contrast, a recent study reported by others. Champeaux and colleagues19 found both STR
reported combined RT and GTR to be a significant predictor of with RT and GTR with RT to be associated with a signifi-
decreased recurrence in patients with AM.13 However, it should cantly decreased recurrence-free survival when analyzed against
be noted that this study employed non-GTR without RT as the STR or GTR, respectively. In our cohort, logistic regression
baseline against which to assess effect on survival, whereas our analysis revealed that RT was more frequently administered in
study specifically compared the effect of RT administration in a cases of STR and cases with combined necrosis and brain invasion
GTR subcohort. (OR = 3.143, P = .001; OR = 3.088, P = .034), which we also

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GARCIA-SEGURA ET AL

Radiotherapy (RT) + No RT + Adjuvant RT

A B 1.00

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Pathology + High mitotic count + Necrosis + Brain invasion + AM variant + Necrosis and brain invasion

1.00 +
+ 0.75

Survival probability
+
0.75 +
+
Survival probability

0.50

0.50

+
+
0.25
0.25 p < 0.0001
p < 0.0001

0.00 0.00
0 50 100 150 200 250 0 50 100 150 200 250
Months until recurrence Months until recurrence

Radiotherapy (RT)
Number at risk Number at risk
Pathology

High mitotic count 20 17 16 16 16 0

Necrosis 35 28 27 26 26 0 No RT 93 83 81 79 79 0
Brain invasion 34 31 31 31 31 0
AM variant 13 10 9 9 9 0 Adjuvant RT 33 17 13 11 11 0
Necrosis and brain invasion 24 14 11 8 8 0 0 50 100 150 200 250
0 50 100 150 200 250 Months until recurrence
Months until recurrence

FIGURE 2. Progression-free survival in patients with atypical meningioma following gross total resection. Kaplan-Meier analysis of PFS after GTR, stratified by A,
pathological predictors (P = .001 with log-rank test) and B, adjuvant radiotherapy (RT) (P = .001 with log-rank test).

+ +
A B
Radiotherapy (RT) No RT Adjuvant RT

Pathology + High mitotic count + Necrosis + Brain invasion + AM variant + Necrosis and brain invasion

1.00
1.00

0.75
0.75
Survival probability

+
Survival probability

+
0.50 +
0.50 +

+
0.25 0.25
p < 0.0001 p = 0.093
+
+
0.00 0.00
0 50 100 150 200 250 0 50 100 150 200 250
Months until recurrence Months until recurrence
Radiotherapy (RT)

Number at risk Number at risk

Pathology

High mitotic count 8 7 6 5 5 0

Necrosis 13 4 3 2 2 0 No RT 26 16 15 14 14 0
Brain invasion 14 12 10 10 10 0 Adjuvant RT 29 16 9 8 8 0
AM variant 6 4 3 3 3 0
Necrosis and brain invasion 14 5 2 2 2 0 0 50 100 150 200 250
0 50 100 150 200 250 Months until recurrence
Months until recurrence

FIGURE 3. Progression-free survival in patients with atypical meningioma following subtotal resection. Kaplan-Meier analysis of PFS after STR, stratified by A,
pathological predictors (P = .001 with log-rank test) and B, adjuvant radiotherapy (RT) (P = .093 with log-rank test).

found to be significantly associated with higher recurrence rates. recurrence might have incorporated cases with combined necrosis
This finding suggests caution in considering these retrospective and brain invasion in their cohort, which our data show to be
data as evidence against the use of adjuvant RT in patients who disparate cohorts. Our data support a concern raised by others
have undergone surgical resection; one could instead forward a that brain invasion may be a poor surrogate for atypical tumor
hypothesis that adjuvant RT was administered to a select cohort grade, as our patients with brain invasion alone represented almost
who were clinically deemed at higher risk of tumor recurrence. half of nonrecurrent cases in our entire cohort.3,21
Lastly, we found brain invasion to be the pathological feature
associated with the longest PFS, regardless of resection type or Limitations
RT status in our cohort. The literature offers mixed support
One important limitation in this study is its observational
regarding the predictive power of brain invasion toward recur-
nature, which could have led to selection bias. Secondly, and
rence.3,7,20-22 It is feasible that some of the studies that have
because of its retrospective nature, adjuvant RT was not randomly
reported a significant association between brain invasion and
allocated to patients but was rather prescribed on the physician’s

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discretion, incurring further risk of bias. Additionally, this study
investigated the effect of adjuvant RT in a qualitative manner,
and thus, the relationship between RT dose and tumor recurrence
was not assessed. Another limitation lies in the designation of
Simpson9 Grading Scale for EOR based on postoperative notes,
which could have introduced variability based on surgeon bias.
Cases were curated using the WHO 2007 grading criteria of AM,
whereas cases in our study underwent resection from 1995 to
2015. To minimize the risk of differential criteria for diagnosis,
cases that underwent resection prior to 2007 were only included
if their pathology report specifically stated the presence of patho-
logical features consistent with WHO 2007 Grade II criteria.
CONCLUSION
We found that STR and administered RT significantly
predicted tumor recurrence. Combined necrosis and brain
invasion was the only pathological feature strongly predictive of
tumor recurrence in our entire cohort, regardless of EOR or RT
administration. We also found brain invasion alone to be a signif-
icant predictor of longer PFS, questioning its inclusion as a main
criterion for AM.
Disclosures
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
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Supplemental digital content is available for this article at www.
neurosurgery-online.com.
Supplemental Digital Content 1. Table. Odds ratio of clinic-pathological factors
associated with adjuvant radiotherapy administration using regression analysis.
Supplemental Digital Content 2. Figure. Progression-free survival in patients
with atypical meningioma by pathology and extent of resection. Kaplan-Meier
analysis of PFS stratified by extent of resection in tumors with A, high mitotic
count (P = .360 with log-rank test), B, necrosis alone (P = .001 with log-rank
test), C, necrosis and brain invasion (P = .031 with log-rank test), and D, brain
invasion alone (P = .103 with log-rank test).
Supplemental Digital Content 3. Figure. Progression-free survival in patients
with atypical meningioma by pathology and radiotherapy. Kaplan-Meier analysis
of PFS stratified by adjuvant radiotherapy (RT) in tumors with A, high mitotic
count (P = .961 with log-rank test), B, necrosis alone (P = .002 with log-rank
test), C, necrosis and brain invasion (P = .001 with log-rank test), and D, brain
invasion alone (P = .129 with log-rank test).
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