Adjuvant radiotherapy delays recurrence following subtotal resection of spinal cord ependymomas

Department of Neurological Surgery, University of California, San Francisco, California (M.C.O., M.E.I., M.Z.S., G.K., M.S., J.M.K., E.T.S., D.A., A.T.P.).
Neuro-Oncology (Impact Factor: 5.56). 12/2012; 15(2). DOI: 10.1093/neuonc/nos286
Source: PubMed
ABSTRACT
Background
Ependymoma is the most common glial tumor of the adult spinal cord. Current consensus recommends surgical resection with gross total resection (GTR) whenever possible. We performed a comprehensive review of the literature to evaluate whether adjuvant radiotherapy after subtotal resection (STR) has any benefit.MethodsA PubMed search was performed to identify adult patients with spinal cord ependymoma who underwent surgical resection. Only patients who had clearly defined extent of resection with or without adjuvant radiotherapy were included for analysis. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of adjuvant radiotherapy on progression-free survival (PFS) and overall survival (OS).ResultsA total of 348 patients underwent surgical resection of spinal cord ependymomas, where GTR was obtained in 77.0% (268/348) of patients. Among those who received STR, 58.8% (47/80) received adjuvant radiotherapy. PFS was significantly prolonged among those who received adjuvant radiotherapy after STR (log rank; P < .001). This prolonged PFS with adjuvant radiotherapy remained significant in multivariate Cox regression analysis (STR versus STR + RT group; hazard ratio (HR) = 2.26, P = .047). By contrast, improved OS was only associated with GTR (GTR versus STR + RT group; HR = 0.07, P = .001) and benign ependymomas (HR = 0.16, P = .001).Conclusions
Surgery remains the mainstay treatment for spinal cord ependymomas, where GTR provides optimal outcomes with longest PFS and OS. Adjuvant radiotherapy prolongs PFS after STR significantly, and OS is improved by GTR and benign tumor grade only.

Full-text

Available from: Michael E Ivan, Mar 18, 2016
Adjuvant radiotherapy delays recurrence
following subtotal resection of spinal
cord ependymomas
Michael C. Oh, Michael E. Ivan, Matthew Z. Sun, Gurvinder Kaur, Michael Safaee,
Joseph M. Kim, Eli T. Sayegh, Derick Aranda, and Andrew T. Parsa
Department of Neurological Surgery, University of California, San Francisco, California (M.C.O., M.E.I.,
M.Z.S., G.K., M.S., J.M.K., E.T.S., D.A., A.T.P.)
Background. Ependymoma is the most common glial
tumor of the adult spinal cord. Current consensus rec-
ommends surgical resection with gross total resection
(GTR) whenever possible. We performed a comprehen-
sive review of the literature to evaluate whether adjuvant
radiotherapy after subtotal resection (STR) has any
benefit.
Methods. A PubMed search was performed to identify
adult patients with spinal cord ependymoma who under-
went surgical resection. Only patients who had clearly
defined extent of resection with or without adjuvant ra-
diotherapy were included for analysis. Kaplan-Meier
and multivariate Cox regression survival analyses were
performed to determine the effects of adjuvant radio-
therapy on progression-free survival (PFS) and overall
survival (OS).
Results. A total of 348 patients underwent surgical re-
section of spinal cord ependymomas, where GTR was
obtained in 77.0% (268/348) of patients. Among
those who received STR, 58.8% (47/80) received adju-
vant radiotherapy. PFS was significantly prolonged
among those who received adjuvant radiotherapy after
STR (log rank; P , .001). This prolonged PFS with adju-
vant radiotherapy remained significant in multivariate
Cox regression analysis (STR versus STR + RT group;
hazard ratio (HR) ¼ 2.26, P ¼ .047). By contrast, im-
proved OS was only associated with GTR (GTR versus
STR + RT group; HR ¼ 0.07, P ¼ .001) and benign
ependymomas (HR ¼ 0.16, P ¼ .001).
Conclusions. Surgery remains the mainstay treatment
for spinal cord ependymomas, where GTR provides
optimal outcomes with longest PFS and OS. Adjuvant
radiotherapy prolongs PFS after STR significantly, and
OS is improved by GTR and benign tumor grade only.
Keywords: ependymoma, extent of resection,
radiotherapy, recurrence, spinal cord, spine .
S
pinal cord ependymomas are the most common
intramedullary glial tumors in adults.
1 7
A large
population-based cancer registry (Surveillance,
Epidemiology, and End Results study) has reported
that ependymomas are more common in the spinal
cord than in intracranial regions across all age groups
(36.2% spine, 22.2% infratentorial, and 11.8% supra-
tentorial), occurring more often in males (56.9%).
8
Although spinal cord ependymomas generally have
better prognosis than do other intramedullary glial
tumors,
4,9
factors affecting prognosis have not been
clearly defined. Some studies indicate that older age
and spinal cord tumor independently had better survival
rates, compared with younger age and intracranial
tumor (either supratentorial or infratentorial), respec-
tively,
10
although a consensus in prognostic factors has
not been reached. Further studies identifying factors im-
portant for improving outcomes are critical to improve
clinical management and prognosis. Ideally, an optimal
treatment paradigm for an individual patient should be
defined based on tumor features, such as histology,
tumor location, radiographic findings, and presenting
symptoms to provide optimal progression-free survival
(PFS) and overall survival (OS).
Factors that have been shown previously to affect
prognosis are tumor grade,
11 13
tumor size,
14
length
of clinical history,
15
preoperative neurological status,
16
presence of distant metastasis,
17
adjuvant radiothera-
py,
14,18 22
and extent of resection.
1,23 27
Among these
factors, extent of resection with gross total resection
(GTR) seems to be the most consistent variable in pre-
dicting improved OS and PFS, whereas others remain
controversial.
3,7,28
Of importance, advancements in
Corresponding Author: Andrew T. Parsa, MD, PhD, Department of
Neurological Surgery, University of California at San Francisco, 505
Parnassus Ave, San Francisco, CA 94117 (pparsaaa@nneurosurg.
ucsfucsf.edu).
Received June 4, 2012; accepted September 25, 2012.
Neuro-Oncology 15(2):208215, 2013.
doi:10.1093/neuonc/nos286
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microsurgical techniques have allowed en bloc GTR
over piecemeal subtotal resection (STR) as the standard
of care for spinal cord ependymomas,
15,16,23 27
despite
a variety of complications associated with surgery.
29
When GTR is not possible, however, because of infiltra-
tion into surrounding spinal cord or nerve roots, many
authors have recommended adjuvant radiothera-
py.
7,14,18 22,28,30
Despite general recommendations supporting the role
of adjuvant radiotherapy,
14,18 22
there are controver-
sies. For example, some studies failed to show significant
improvement in postoperative outcomes
26,31
with added
morbidity associated with radiation.
3,32 34
To help
clarify this controversy, we performed a comprehensive
review of the literature on patients with classic spinal
cord ependymoma (World Health Organization
[WHO] grade II and III) who underwent surgical resec-
tion to determine whether adjuvant radiotherapy im-
proves tumor control.
Materials and Methods
Article Selection
A comprehensive systematic review of the English-
language literature was performed. An integrative analysis
was performed, in which individual patient data from
studies were pooled and statistically analyzed. Aggre-
gated data sets, in which individual patient data were
grouped, were not included in this analysis because the
goal of the study was to analyze the individual patient
data with long follow-up periods to allow analysis of PFS
and OS with use of Kaplan-Meier and Cox regression sur-
vival analyses. Articles were identified via PubMed search
using the key word “ependymoma;” this resulted in 3765
articles published from 1965 through 2011. All articles
were individually reviewed to identify patients with surgi-
cal spinal cord ependymoma in which the extent of resec-
tion (GTR vs. STR) was clearly identifiable. We initially
identified 80 articles with a total of 425 patients who
met the criteria. Seventy-seven of these patients with myx-
opapillary ependymomas, WHO grade I tumors, were not
included in the analysis. The remaining 348 patients from
68 articles with WHO grade II and III spinal cord ependy-
momas were analyzed.
16,20,21,25,27,30,3596
Weighted
meta-analysis (i.e., 5- and 10-year PFS and OS) could not
be performed because these statistics were not consistently
reported in large aggregated studies. The median
follow-up period for all patients was 48 months, and the
number of patients included from each study varied from
1 to 30 patients.
Data Extraction
Data from case reports and institutional series were ex-
tracted with the following information: age, sex, extent
of resection (GTR vs. STR), adjuvant radiotherapy, mor-
bidity, recurrence or progression of disease, time to re-
currence or progression of disease, mortality, time to
mortality, and duration of follow-up. Treatment
paradigms were stratified into 4 groups: GTR, GTR +
RT, STR, or STR + RT. Survival analyses were per-
formed for GTR, STR, and STR + RT groups because
the main goal of the study was to determine the role of
adjuvant radiotherapy in patients receiving STR.
Patients who underwent biopsy or surgery with chemo-
therapy were excluded.
Statistical Analysis
PFS and OS were analyzed using building Kaplan-Meier
curves, and differences were assessed using log rank or
Tarone-Ware (when curves cross each other) test. This
analysis was followed by Cox proportional hazards anal-
ysis by backward stepwise model selection to adjust for
confounding variables including age, sex, extent of resec-
tion, tumor grade (WHO II vs. III), morbidity, tumor lo-
cation (upper: cervicomedullary to cervicothoracic;
lower: thoracic, lumbar, and conus), and radiation treat-
ment. Hazard ratios (HRs) with 95% confidence inter-
vals (CIs) were estimated. Continuous variables were
analyzed using the t test or analysis of variance with
post hoc Tukey test, and categorical values were analyzed
using the Pearson’s x
2
test. Fisher’s exact test was used
if the expected cell count in a cont ingency table was
,5. P , .05 was considered to be statistically significant.
Analyses were performed using the statistical software
package SPSS, version 20 (SPSS).
Results
Clinical Characteristics
The literature search yielded a total of 68 manuscripts
with a total of 348 patients who underwent surgical treat-
ment for classic spinal cord ependymomas with clearly
identifiable extent of resection.
16,20,21,25,27,30,35 96
The
mean age was 41.0 years with a range of 1873 years,
and there were more males (57.6%) than females
(42.4%) overall (Table 1).
Of 348 patients, 268 (77.0%) received GTR, and the
remaining 80 (23.0%) received STR. In the STR group,
47 (58.8%) of 80 received adjuvant RT, and only 10
(3.7%) of 268 received adjuvant radiotherapy after
GTR. We grouped tumors into benign (WHO grade II)
or anaplastic (WHO grade III) ependymomas. Overall,
11 (3.4%) of 319 tumors were anaplastic. The number
of anaplastic ependymomas differed significantly
across treatment paradigms with significant ly more ana-
plastic tumors in the STR groups (8 [11.3%] of 71),
compared with the GTR groups (3 [1.2%] of 248; P ,
.001) (Table 1). Moreover, ependymomas in the lower
spinal cord had significantly lower GTR rate (67.2%,
88 of 131), compared with the tumors in the upper
spinal cord (83.0%, 180 of 217; P , .001).
Adjuvant RT Improves PFS after STR
We first performed Kaplan-Meier analysis to determine
whether adjuvant radiotherapy had a significant effect
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on PFS and OS after STR. It was clear from our analysis
that GTR provided the best PFS and OS (log rank,
P , .001; Fig. 1 and 2). Of importance, adjuvant RT sig-
nificantly prolonged PFS in the STR group. The median
survival time (50% PFS) was 48 months in the STR
group, which was doubled to 96 months with adjuvant
radiotherapy in the STR + RT group. Because of lack
of sufficient events, median survival times could not be
calculated for the GTR group. Five-year PFS rates for
GTR, STR + RT, and STR groups were 97.9%,
65.3%, and 45.1%, respectively, with 20.2% improve-
ment in PFS with adjuvant RT after STR. In contrast
to PFS, adjuvant radiotherapy did not improve OS sig-
nificantly in patients who received STR (pairwise
Tarone-Ware, P ¼ .643). Five-year OS for GTR,
STR + RT, and STR groups was 98.8%, 79.3%, and
73.7%, respectively.
Our previous analysis, however, revealed that the
grades of tumors were significantly different across dif-
ferent treatment paradigms (Table 1); this could be re-
sponsible for the differences found in Kaplan-Meier
analysis. Thus, we performed multivariate Cox propor-
tional hazards analysis to determine wheth er adjuvant
RT prolongs PFS after STR while accounting for other
possible confounding variables, including age, sex,
extent of resection, grade of tumor (WHO II vs III), mor-
bidity, and tumor location. We found that different
treatment paradigms resulted in significant difference
in PFS (Table 2). Of most importance, STR alone had
an HR of 2.26 (95% CI ¼ 1.015.07; P ¼ .047), com-
pared with STR + RT. Consistent with the Kaplan-
Meier analysis, GTR provided the best PFS outcomes ,
with HR of 0.06 (95% CI ¼ 0.02 0.23; P , .001),
compared with STR + RT. Furthermore, tumor grade
remained significant in the analysis, with anaplastic
WHO grade III tumors having HR of 2.88 (95% CI ¼
1.137.34; P ¼ .026), compared with benign WHO
grade II tumors. Other variables did not remain signifi-
cant and were dropped from the analysis.
We then performed the same multivariate Cox regres-
sion analysis for OS while accounting for the same con-
founding variables (Table 3). In contrast to PFS, there
were no significant improvements in OS with adjuvant
RT after STR (STR: HR 1.01, P ¼ .99, when compared
with STR + RT). Best OS outcomes were achieved with
GTR (HR 0.07, P ¼ .001, 95% CI ¼ 0.02 0.36, when
compared with STR + RT). Tumor grade was again
found to be a significant variable, with anaplastic
tumors having HR of 6.08 (95% CI¼ 2.01 18.37;
P ¼ .001), compared with benign tumors. As before,
other variables did not remain significant and were
dropped from the analysis.
Radiation Dose Does Not Affect Recurrence or Survival
There is some evidence that total dose of radiotherapy
may influence clinical outcomes in patients with spinal
cord ependymomas who undergo STR.
30
A study by
Shaw et al., for example, used a median dose of 50 Gy,
with a range of 3657 Gy, and suggested that total
dose .50 Gy may be superior.
3,30
Thus, we stratified
Table 1. Demographic characteristics of patients who underwent surgical resection for spinal cord ependymomas
Characteristic GTR GTR 1 RT STR STR 1 RT
P
N 258 10 33 47
Mean age + SEM 41.9 + 0.8 39.0 + 4.2 39.7 + 2.6 37.2 + 2.2 .176
a
Gender (male) 56.4% 62.5% 58.1% 63.2% .874
b
Anaplastic ependymomas 0.8% (2/238) 10% (1/10) 13.3% (4/30) 9.8% (4/41) ,.001
c
Location of tumor
Upper 68.6% (177/258) 30% (3/10) 42.4% (14/33) 48.9% (23/47)
Lower 31.4% (81/258) 70% (7/10) 57.6% (19/33) 51.1% (24/47) ,.001
b
Mean age and gender did not differ across different treatment paradigms, while number of anaplastic ependymomas and location of
tumors, broadly divided into upper and lower spinal cord, were significantly different across different treatment paradigms.
a
Analysis of variance.
b
x
2
test.
c
Fisher’s exact.
Fig. 1. PFS by treatment paradigm. We built Kaplan-Meier curves
to determine whether adjuvant RT prolongs PFS among patients
who receive STR for spinal cord ependymomas. As seen in this
figure, GTR provides the best PFS, which was significantly longer,
compared with STR and STR + RT groups (log rank, P , .001).
The median survival time (50% PFS) for the STR + RT group was
twice as long (96 months), compared with the STR group
(48 months).
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the patients treated with adjuvant RT into 2 groups:
those treated with ,50 Gy (40.7 + 2.2 Gy; range, 20
48.6; n¼ 16) and those treated with 50 Gy (51.8 +
0.5; range, 5060 Gy; n ¼ 24) of total radiation. The
dose of radiation given was available for 40 patients,
with 16 patients receiving , 50 Gy and the remaining
24 patients receiving 50 Gy of total radiation.
Overall, there were 6 recurrences in the , 50 Gy group
(37.5%) and 10 in the 50 Gy group (41.7%). We
again constructed Kaplan-Meier curves, which showed
that there were no significant differences between the 2
groups in PFS (P ¼ .559) or OS (P ¼ .510; Fig. 3A and
B). Moreover, radiation dose did not remain as a signifi-
cant variable in multivariate Cox regression analysis for
both PFS and OS while accounting for other important
confounding variables, such as extent of resection and
tumor grade (data not shown).
Discussion
Although adjuvant RT is routinely given by most
providers after STR of spinal cord ependymomas, the
benefit with respect to prolonging PFS and OS is contro-
versial.
14,18,19,21,22,26,31
Moreover, the recommended
Table 2. Multivariate Cox proportional hazards analysis of PFS
Variable HR 95% CI
P
STR + RT 1
GTR 0.06 0.020.23 ,.001
STR 2.26 1.015.07 .047
WHO grade III 2.88 1.137.34 .026
We performed backward stepwise model selection to determine
the PFS benefit of adjuvant radiation treatment in patients who
received STR while accounting for age, gender, extent of
resection, tumor grade (WHO grade II vs. III), morbidity, and
tumor location (upper: cervicomedullary to cervicothoracic, lower:
thoracic, lumbar, and conus). We used STR + RT groups as the
control for comparison. Only treatment paradigms and tumor
grade remained significant in the analysis, with significantly
improved PFS in the STR + RT group compared to STR group.
Table 3. Multivariate Cox proportional hazards analysis of OS
Variable HR 95% CI
P
STR + RT 1
GTR 0.07 0.020.36 .001
STR 1.01 0.333.03 .99
WHO grade III 6.08 2.0118.37 .001
We performed backward stepwise model selection to determine
the OS benefit of adjuvant radiation treatment in the STR group
while accounting for age, gender, extent of resection, tumor
grade (WHO grade II vs. III), morbidity, and tumor location
(upper: cervicomedullary to cervicothoracic, lower: thoracic,
lumbar, and conus). Similar to PFS, only treatment paradigms and
tumor grade remained significant in the analysis, but only GTR
remained as the beneficial variable for improving OS with no
improvement with adjuvant radiotherapy in the STR groups.
Fig. 3. Kaplan-Meier analysis of PFS and OS, by radiation dose.
Neither PFS (A; P ¼ .559) nor OS (B; P ¼ .510) were significantly
affected by radiation dose (,50 Gy vs. 50 Gy). These results
were confirmed with multivariate Cox regression analysis (data
not shown).
Fig. 2. OS, by treatment paradigm. In accordance with PFS, GTR
provided the best OS, which was statistically longer, compared
with that among STR or STR + RT groups (log rank; P , .001).
However, there was no difference in OS between the STR and
STR + RT groups.
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dose of radiation has not been clearly defined
30
because
high doses of radiation may be associated with increased
risk of radiation myelopathy.
32 34
Thus, we performed
a comprehensive review of the literature by performing
an integrative analysis (in which the previously reported
individual cases are pooled and analyzed) to determine
whether adjuvant RT can prolong PFS in patients with
spinal cord ependymoma, specifically focusing on
those who received STR.
Our results indicate that 77.0% of patients with spinal
cord ependymoma who undergo surgical resection re-
ceived a GTR. This treatment paradigm provides the best
outcomes in terms of both PFS and OS (Fig. 1 and 2),
which is consistent with previous reports.
15,16,23 27
Five-year PFS and OS rates were 97.9% and 98.8%, re-
spectively, in our study, suggesting that GTR can
provide a definitive cure in most cases. Thus, GTR
should be the goal of every spinal cord ependymoma
surgery if significant neurological morbidity can be
avoided.
29
Spinal cord ependymomas that are subtotally resected
tend to recur at rates up to 50%70% without adjuvant
therapy,
2,7,97
which is consistent with the findings in our
current study. Five-year recurrence rate after STR was
54.9%, with 5-year survival rate of 73.7% in this
study. This high recurrence rate has promoted the use
of adjuvant RT for patients receiving STR,
14,19 21
al-
though without clear evidence supporting improved out-
comes. For example, a study by Celli et al. showed that
postoperative RT did not affect outcomes in patients
with filum terminale ependymomas.
26
By contrast, a
study by a group at the MD Anderson Cancer Center
found favorable outcomes with adjuvant RT for myxo-
papillary ependymomas,
18
which most often occur in
the filum terminale. A study by Abdel-Wahab et al.
found that adjuvant RT prolonged PFS in a univariate
Cox proportional hazards model,
31
and this was found
to be not significant in a multiva riable model. Clearly,
one of the major difficulties in analyzing outcomes
with different treatment paradigms has been to
account for other confounding factors, such as grade
of tumor and extent of resection. Thus, in this report,
we performed a Kaplan-Meier and Cox regression sur-
vival analyses on patients with previously reported
spinal cord ependymoma to determine whether adjuvant
RT improves tumor control after STR.
Overall, our analysis showed a significantly pro-
longed PFS with adjuvant RT after STR. Five-year PFS
was improved by 20.2% from 45.1% in the STR
group to 65.3% in the STR + RT group. Because these
results may have been confounded by the higher percent-
age of anaplastic ependymomas in the STR group
(13.3%), compared with the STR + RT group (9.8%),
we performed multivariate Cox regression analysis to
account for other confounding variables, including
tumor grade. This analysis confirmed prolonged PFS
with adjuvant RT after STR in our dataset.
Surprisingly, OS among patients receiving STR was
not affected by adjuvant RT. This could be attributable
to the benign nature of the majority of spinal cord epen-
dymomas with low mortality rates. Moreover, it was
difficult to discern the true etiology of mortality in
these patients on the basis of their description in the lit-
erature. It is possible that patients die more often of com-
plications related to their disease (such as neurological
deficits, immobility, deep venous thrombosis, and infec-
tions) and not directly due to disease recurrence. If such
were the case, one would not expect to see similar corre-
lations between PFS and OS, which may be partly re-
sponsible for the variable beneficial results for PFS and
OS with adjuvant RT in the STR group.
The optimal dose of radiation for subtotally resected
spinal cord ependymomas also still remains to be deter-
mined. A study by Shaw et al. found that 6 (35%) of 7
patients who received 50 Gy postoperative RT re-
curred, and only 1 (20%) of 5 recurred after receiving
.50 Gy. Thus, they recommended delivering a total
dose of 55 Gy, regardless of extent of surgery.
30
In our
study, however, we found no difference in outcomes
for PFS and OS based on radiation dose, in both univar-
iate and multivariate analyses. However, it is likely that
there are many other confounding variables, such as
whole spine versus local radiation, tumor grade, and his-
tology, which may affect outcomes. Further studies are
needed to delineate the effects of these variables. Most
authors currently recommend doses of 4554 Gy with
long-term follow-up because recurrence can occur
many years after initial treatment.
19
Because this is a retrospective integrative analysis of
pooled individual patient data from multiple studies,
there are clear inherent limitations involved with this
method. Studies in general may be more likely to only
report cases with good outcomes, and thus, our results
may be biased toward better outcomes than in reality.
Furthermore, the differences in patient treatment at dif-
ferent institutions, such as surgeon’s experience,
whether adjuvant RT is used, follow-up protocol, and
protocols involving treatment of recurrent tumors,
were not taken into account and may have affected
results presented in this study. Specifically, individual
patient data used in this study may not completely
reflect the patients with spinal cord ependymoma as a
whole. Because aggregated patient data (where individu-
al patient data are grouped) were not used in this study,
our results can be biased by individual case reports or
smaller studies presented by institutions with a relatively
less experience in treating patients with spinal cord epen-
dymomas. Although our study did not include some
large studies that did not report individual patient
data, a number of publications used in our study con-
tained cohorts of patients . 20 from authors with signif-
icant experience with spinal cord ependymoma
surgery.
16,20,25,35,39,56,58,60,83
Our results, thus, could
represent the sum of results achieved at large referral
centers to small institutions with relatively fewer experi-
ences with spinal cord ependymomas and may not repre-
sent similar results obtained at busy institutions with
large volumes of patients with spinal cord ependymoma.
Overall, our findings would be best confirmed in a
prospectively randomized trial conducted at multiple in-
stitutions with the capacity to treat spinal cord
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ependymomas with use of both surgical resection and
adjuvant RT.
In summary, our results indicate that adjuvant RT
can prolong PFS in patients with spinal cord ependy-
moma who receive STR, and OS is only improved by
GTR and benign tumor grade. GTR provides optimal
outcomes with longest PFS and OS, and thus, GTR
should be the main goal of every spinal cord ependy-
moma surgery. When STR is the best achievable surgical
outcome, adjuvant RT should be strongly considered
with careful long-term follow-up.
Conclusion
Our results show that best outcomes for spinal cord
ependymomas are achieved with GTR, which is consis-
tent with previous findings.
3,7,28
Moreover, adjuvant
RT can prolong PFS among patients who receive STR.
Although adjuvant RT may not ultimately affect OS, de-
creasing recurrence can appreciably benefit patient
outcomes by avoiding repeated surgeries, which are
associated with significant morbidities.
29
Prolonged sur-
veillance is recommended, regardless of extent of surgery
or adjuvant therapies because recurrence can occur
many years after surgical resection of spinal cord
ependymomas.
Acknowledgments
Conflict of interest statement. None declared.
Funding
This work was supported by National Research
Service Award from the National Institutes of Health
(F32NS073326-01 to M. C. O.) and Reza and Georgianna
Khatib Endowed Chair in Skull Base Tumor Surgery
(to A.T. P.).
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  • Article: Ependymomas
    [Show abstract] [Hide abstract] ABSTRACT: Ependymomas are the third and least common major group of gliomas after astrocytomas and oligodendrogliomas. They have distinctive histopathologic appearances and have only limited histological differential diagnoses in selected instances. They are classified by the World Health Organization into 3 grades, with grade I comprising the special subtypes of subependymoma and myxopapillary ependymoma and grade III being “anaplastic” tumors with a high local recurrence rate and a significant capacity to disseminate both in cerebrospinal fluid and hematogenously. Grade II ependymomas include classic, “cellular,” papillary, and tanycytic variants. Prognosis for each is related to patient age, tumor location (supratentorial vs posterior fossa vs spinal cord), extent of surgical resection, and histopathologic type and grade, but pathological grading is far from reliable. Molecular profiles of ependymomas are being developed but have not yet reached clinically useful status for directing therapy.
    No preview · Article · Sep 2013 · Pathology Case Reviews
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution. Methods: Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival. Results: The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% (n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location (P < .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not by radiation (P < .01), as significantly increasing risk of early progression. Conclusions: We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies.
    No preview · Article · Aug 2014 · Neuro-Oncology
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Background: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). Methods: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. Results: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). Conclusions: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.
    Full-text · Article · Nov 2014 · The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
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