We report a series of 10 patients with thalamic high HGGs with extensive clinical, neuro-radiological, and pathologic analyses. Moreover, we attempted to correlate survival with some of the clinical data and reviewed the literature with regards to the management of thalamic HGGs.

1. Outcomes
of
High-­‐Grade
Thalamic
Gliomas
in
a
Cancer
Centre
Mary
Ondinee
Manalo1,
Joycelyn
Lee1,
Tham
Chee
Kian1
1Department
of
Medical
Oncology,
Na7onal
Cancer
Centre
Singapore
Correspondence:
tham.c.k@nccs.com.sg
BACKGROUND
High-­‐grade
gliomas
(HGGs)
of
the
thalamic
region
are
rare
and
comprise
<5%
of
all
intracranial
brain
tumors.
They
are
generally
difficult
to
treat
because
the
tumors
are
located
deep
within
the
brain
and,
therefore,
are
rarely
amenable
to
radical
surgical
resec7on.
Although
temozolamide
plus
radia7on
therapy
followed
by
maintenance
temozolamide
(TMZ
+
RT
à
TMZ)
has
improved
survival
in
glioblastoma,
median
overall
survival
for
unresected
tumors
remains
poor
at
9.4
months.
We
report
a
series
of
10
pa7ents
with
thalamic
high
HGGs
with
extensive
clinical,
neuro-­‐radiological,
and
pathologic
analyses.
Moreover,
we
aXempted
to
correlate
survival
with
some
of
the
clinical
data
and
reviewed
the
literature
with
regards
to
the
management
of
thalamic
HGGs.
METHODS
The
database
of
the
Neuro-­‐
Oncology
service
of
the
Na7onal
Cancer
Centre
Singapore
Medical
Oncology
Department
was
reviewed
to
iden7fy
pa7ents
with
primary
thalamic
HGGs
(glioblastoma
[GB],
anaplas7c
astrocytoma
[AA],
anaplas7c
oligoastrocytoma
[AOA],
anaplas7c
oligodendroglioma
[AOD])
treated
between
January
2010
to
J a n u a r y
2 0 1 5 .
A l l
c l i n i c a l ,
neuroradiological,
histopathological
data
were
retrospec7vely
reviewed.
Treatment,
complica7ons
and
survival
were
also
noted.
Moreover,
we
aXempted
to
correlate
survival
with
clinical
data
and
reviewed
l i t e r a t u r e
w i t h
r e g a r d s
t o
management
of
thalamic
HGGs.
RESULTS
Between
January
2010
and
January
2015,
ten
pa7ents
met
the
entry
criteria
for
the
study.
There
were
7
males
and
3
females,
with
a
median
age
of
51
yrs
(mean
46
yrs,
range
17-­‐72
yrs).
Pa7ents
who
had
WHO
grade
III
lesions
had
a
younger
mean
age
at
diagnosis
(mean
32
yrs)
than
those
pa7ents
with
WHO
grade
IV
(mean
51
yrs).
The
dura7on
of
symptoms
before
diagnosis
was
short
ranging
from
one
week
to
two
months
at
most.
None
underwent
resec7on.
Four
pa7ents
underwent
further
chemotherapy
upon
progression.
Lines
of
chemotherapy
received
by
the
pa7ents
are
as
follows:
four
PCV,
three
single-­‐agent
bevacizumab
(BV),
two
BV
plus
irinotecan,
one
lomus7ne
plus
BV,
and
one
carbopla7n
plus
BV.
Clinicoradiological
features and treatment
details
WHO grade III
lesions
(3 patients, 30%)
WHO grade IV
lesions
(7 patients, 70%)
Total
n=10
Mean age, years 32 (17-62) 52 (18-72) 46 (17-72)
<50 years 2/3 (67%) 3/7 (43%) 5/10 (50%)
≥50 years 1/3 (33%) 4/7 (57%) 5/10 (50%)
Gender
Male 1/3 (33%) 6/7 (86%) 7/10 (70%)
Female 2/3 (67%) 1/7(14%) 3/10 (30%)
Side of lesion
Right 1/3 (33%) 5/7 (71%) 6/10 (60%)
Left 1/3 (33%) 2/7 (28%) 3/10 (30%)
Bilateral 1/3 (33%) 0/7 1/10 (10%)
Clinical presentation
Motor deficits 0/3 5/7 (71%) 5/10 (50%)
Raised ICP 2/3 (67%) 3/7 (43%) 5/10 (50%)
Visual changes 1/3 (33%) 4/7 (57%) 5/10 (50%)
Expressive aphasia 1/3 (33%) 2/7 (28%) 3/10 (30%)
Altered sensorium 1/3 (33%) 1/7 (14%) 2/10 (20%)
Seizures 1/3 (33%) 0/7 1/10 (10%)
MRI features
Perilesional edema 3/3 (100%) 7/7 (100%) 10/10 (100%)
Enhancement 3/3 (100%) 7/7 (100%) 10/10 (100%)
Hydrocephalus 3/3 (100%) 4/7 (57%) 7/10 (70%)
Hemorrhage 2/3 (67%) 2/7 (28%) 4/10 (40%)
Central necrosis 1/3 (33%) 0/7 1/10 (10%)
Cyst 0/3 1/7 (14%) 1/10 (10%)
Surgical details
Stereotactic biopsy 1/3 (33%) 5/7 (71%) 6/10 (60%)
Endoscopic biopsy 2/3 (67%) 2/7 (28%) 4/10 (40%)
VP shunt 3/3 (100%) 3/7 (43%) 6/10 (60%)
External drain 2/3 (67%) 1/7 (14%) 3/10 (30%)
Cyst aspiration 0/3 1/7 (14%) 1/10 (10%)
Radiotherapy
Yes 2/3 (67%) 7/7 (100%) 9/10 (90%)
No 1/3 (33%) 0/7 1/10 (10%)
Chemotherapy
Concomitant TMZ 2/3 (67%) 6/7 (86%) 8/10 (80%)
Maintenance TMZ 2/3 (67%) 4/7 (57%) 6/10 (60%)
2nd line chemotherapy 2/3 (67%) 2/7 (28%) 4/10 (40%)
Pt
#
Age/
Sex
Histology Initial
Treatment
PFS
(months)
OS
(months)
Clinical
status
1 69/M GB TMZ +
RT
1.7 5.6 Dead
2 62/M AOA None 0.6 5.4 Dead
3 18/M GB TMZ + RT à
TMZ x 3
9.3 17.9 Dead
4 58/F GB TMZ + RT à
TMZ x 2
4.4 6.5 Dead
5 17/F AA TMZ + RT à
TMZ x 4
3.9 12.9 Dead
6 34/M GB TMZ + RT à
TMZ x 12
17.5 18.8 Alive (PD)
7 67/M GB TMZ + RT 2.1 5.7 Dead
8 17/F AOA TMZ + RT à
TMZ x 6
7.9 21.6 Dead
9 72/M GB RT 2.5 9.1 Alive (PD)
10 44/M GB TMZ + RT à
TMZ x 6
18.2 22 Alive (PD)
COMPARISON
BETWEEN
GRADE
III
AND
GRADE
IV
INITIAL
TREATMENT
AND
OUTCOME
PrognosJc
Factor
Mean
OS
(months)
Overall
Survival
HR
(95%
CI)
Log
rank
p-­‐value
Histology
Grade III 17.4 1.00 0.515
Grade IV 12.2 1.66
Age
< 50 yrs 18.6 1.00 0.013
≥ 50 yrs 6.5 1.61
Symptom duration
> 1 month 11.8 1.00 0.097
≤ 1 month 13.1 1.31
Sex
Male 10.4 1.00 0.412
Female 15.8 0.48
Treatment
RT+TMZ 13.4 1.00 0.002
No RT+TMZ 5.4 1.41
UNIVARIATE
ANALYSIS
PROGRESSION-­‐FREE
SURVIVAL
OVERALL
SURVIVAL
SURVIVAL
DATA
CONCLUSION
With
a
median
follow-­‐up
of
11
months,
the
median
PFS
in
all
10
pa7ents
was
3.9
months
(range
0.6
–
18.2
months)
and
the
median
OS
was
9.1
months
(range
5.4
–
22
months).
The
1-­‐year
PFS
and
OS
of
all
pa7ents
were
23%
(95%
confidence
interval
(CI)
4
-­‐
53%)
and
48%
(95%
CI,
16-­‐74%),
respec7vely.
Overall,
seven
pa7ents
died
with
a
mean
OS
of
10.8
months
for
this
group.
Three
pa7ents
were
s7ll
alive
at
the
end
of
study.
All
had
progressive
disease.
Pa7ents
who
were
less
than
50
years
had
a
significantly
longer
PFS
(p=0.0226)
and
OS
(p=0.0133)
compared
with
younger
pa7ents.
Administra7on
of
treatment
with
TMZ
and
radia7on
was
significantly
associated
with
beXer
PFS
(p=0.0027)
and
OS
(p=0.0226).
Histology,
symptom
dura7on
prior
to
diagnosis,
and
sex
were
not
significantly
associated
with
OS.
Our
study
confirms
the
dismal
prognosis
for
pa7ents
with
HGGs
of
the
thalamus
as
compared
with
hemispheric
HGGs.
The
median
OS
in
our
series
is
similar
to
the
median
OS
of
adult
thalamic
HGGs
from
other
series
and
unresected
GBs
in
general.
Younger
pa7ents
have
beXer
survival
and
this
has
also
been
shown
in
other
previous
studies.
Standard
of
treatment
remains
to
be
TMZ
+
RT
à
TMZ.
More
aggressive
treatments
in
the
upfront
sekng
prior
to
TMZ
+
RT
may
increase
survival.
Development
of
new
treatment
strategies
tailored
for
this
par7cular
set
of
pa7ents
by
a
mul7disciplinary
team
is
needed.
Median
OS:
9.1
months
1-­‐yr
OS:
48%
(95%
CI,
16-­‐74%)
Median
PFS:
3.9
months
1-­‐yr
PFS:
23%
(95%
CI,
4-­‐53%)