Adu|t 8ra|n 1umors

aul 8rown, Mu
Mu Anderson Cancer CenLer
PousLon, 1x
ueepak khunua, Mu
unlverslLv of Wlsconsln, Madlson, Wl
WesLern 8adlauon Cncoloav, MounLaln vlew, CA
ulsclosure
ueepak khunua
ConsulLanL for rocerLus, lnc
Speaker for 1omoLherapv
CranL supporL from 1omoLherapv
aul 8rown
none
Learnlna Cb[ecuves
ulscuss Lhe lncldence, prevalence, morLallLv, morbldlLv, and
cllnlcal lmpacL of Lhe ma[or mallananL and benlan adulL
prlmarv CnS Lumors
8ecoanlze Lhe subsLanual heLeroaenelLv LhaL exlsLs wlLhln
Lhese Lumor Lvpes and undersLand Lhe proanosuc and
predlcuve varlables allowlna for approprlaLe selecuon of
Lherapeuuc cholces, Lallored for a speclc pauenL
Lxplaln Lhe ma[or levels of evldence for Lherapeuuc declslon-
maklna
AppreclaLe Lhe role of varlous Lheraples, especlallv suraerv
radloLherapv and chemoLherapv ln manaalna Lhese Lumors
T1 post-contrast T2
*Walker MD, et al. N Engl J Med. 1980;303:1323-1329.
Andersen AP. Acta Radiol Oncol Radiat Phys Biol. 1978;17:475-484. Walker MD, J Neurosurg.
1978;49:333-343.
Walker MD, NEJM 1980;303:1323-1329.Kristiansen K, Cancer. 1981;47:649-652.
K. KRISTIANSEN,Cancer 47:649-652, 1981.
Keime-Guibert (France) et al. NEJM 356:1527-35, 2007.
*Trial discontinued early due to planned interim analysis
Contro
l
RT P-value
Median
OS
3.9 mo 6.7
mo
0.002
Roa (Canada) et al. JCO 22:1583-88, 2004.
*KPS = 70
60 Gy 40 Gy French
Median
OS
5.1 mo 5.6
mo
6.7 mo
Technical
Brachytherapy
IMRT
Intraoperative RT
Radiosurgery
Proton-beam
therapy
Biological
Hypofractionation
Hyperfractionation
Accelerated RT
Radiolabeled
antibodies
Radiosensitizers
60 Gy is standard. No proof for higher doses that
increase toxicity
Souhami L. et al. Int J Radiat Oncol Biol Phys. 2004;60:853-860.
Radiosurgery has not been proven to prolong survival of
GBM patients.
The role of maximal resection controversial
Vuorinen V et al. Acta Neurochir 145:5-10, 2003
Survival benefit, trend benefit time to deterioration, p=0.057.
Impact of Resection on Survival
in Malignant Glioma
Stummer W (Germany) et al. Lancet Oncology 7:392-401, 2006.
5-ALA=aminolevulinic acid
*97% GBM
Impact of Resection on Survival
in Malignant Glioma
Stummer W (Germany) et al. Lancet Oncology 7:392-401, 2006.
1. Gilbert M, et al. J Clin Oncol. 1998;16:3851-3857.
2. Newlands ES, et al. 33rd Ann. Mtg. of ASCO. May 17-21, 1997. Abstract 1403.
3. van Rijn J, et al. Int J Radiat Oncol Biol Phys. 2000;47:779-784.
4. Stupp R, et al. J Clin Oncol. 2002;20:1375-1382.
5. Combs, et al. ASCO 2004.
Focal RT daily 30 x 200 cGy
Total dose 60 Gy
Temozolomide 75 mg/m
2
po qd for 6 weeks,
then 150-200 mg/m
2
po qd day 1-5 q 28 days for 6 cycles
Concomitant
TMZ/RT*
Adjuvant TMZ
Weeks 6 10 14 18 22 26 30
RT Alone
R
0
*PCP prophylaxis was required for patients receiving TMZ during the concomitant phase.
EORTC/NCIC Phase III GBM Trial:
Overall Survival
months
0 6 12 18 24 30 36 42
0
10
20
30
40
50
60
70
80
90
100
TMZ/RT
RT
P
e
r
c
e
n
t
a
g
e

Note: Progression varied
from center to center
P<0.0001
Stupp R, et al. N Engl J Med. 2005;352:987-996.
MGMT RT +TMZ RT +TMZ
Overall 36 54 10 26
Unmethylated 35 40 2 14
Methylated 48 69 23 46
GBM patients with methylated MGMT from EORTC trial 2-
year survival 14% vs 46%.
% 6-mo PFS % 2-yr survival
Hegi ME, et al. N Engl J Med. 2005;352:997-1003.
Stupp ME, et al. Lancet Oncology. 2009;10:459-66.
5 yr OS for entire RT/TMZ arm -> 10%
Athanassiou, et al. JCO 23(10): 2372-2377, 2005
Athanassiou, H. et al. J Clin Oncol; 23:2372-2377 2005
TMZ daily x 6 wks
R
Radiotherapy (30 x 2 Gy)
Concomitant Phase
Adjuvant Phase (12 mo)
Dose dense TMZ
(100 mg/m2 daily x 21d)
Stratify by:
MGMT methylation
RTOG/EORTC 0525
N = 1100+
Trial Completed
Goli (Duke), et al. abstract #2003, Clinical Science Symposium ASCO 2007.
Vredenburgh JCO, 2007
Yung WKA, et al. Br J Cancer. 2000;83:588-593.
Goli, et al. abstract #2003, Clinical Science Symposium ASCO 2007.
Cloughesy, et al. abstract #2010, oral presentation ASCO 2008.
Sample Size= 720
Primary endpoints:
OS and PFS
SSSample Size= 7 SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS
Taal W., et al. abstract #2009, oral presentation ASCO 2007.
GBM - Conclusions
GBM - Conclusions
Wolfgang et al. JCO 27:5874-5880, 2009. RT 60 Gy/30
318 patients 1/2 Astrocytoma, 1/3 oligoastrocytoma, 1/8 oligodendroglioma
80% power to detect 50%improvement TTF w/ chemo one sided level 0.05
Wolfgang et al. JCO 27:5874-5880, 2009.
* TTF defined as failure after both chemo AND RT requiring new chemotherapy
Wolfgang et al. JCO 27:5874-5880, 2009.
Wolfgang et al. JCO 27:5874-5880, 2009.
Wolfgang et al. JCO 27:5874-5880, 2009.
*Maximal F/U 54 months
Wolfgang et al. JCO 27:5874-5880, 2009.
Phase I
Arm 1: XRT + BCNU 200 mg/m
2
+ TMZ 150 mg/m
2
x 5d q 8 wks
15 pts enrolled: 7/10 eligible pts needed dose mods
Arm 5: XRT + TMZ 150 mg/m
2
x 5d + BCNU 150 mg/m2 q 8 wks
15 pts enrolled. Combination produces unacceptable toxicity
Phase III n=480
Arm 2: XRT + TMZ 150 mg/m
2
x 5d q 4 wks
Closed early: 201 patients enrolled
Chang SM, et al. Neuro-Onc 10:826, 2008. *CCNU allowed
TMZ combined with RT significantly
better tolerated than BCNU
Chang SM, et al. Neuro-Onc 10:826, 2008
Focal RT daily 30 x 200 cGy
Total dose 60 Gy
Temozolomide 75 mg/m
2
po qd for 6 weeks,
then 150-200 mg/m
2
po qd day 1-5 q 28 days for 6 cycles
Concomitant
TMZ/RT*
Adjuvant TMZ
Weeks 6 10 14 18 22 26 30
RT Alone
R
0
*PCP prophylaxis was required for patients receiving TMZ during the concomitant phase.
573 patients accrued. 76% received adjuvant TMZ, 36% all 6 cycles
months
0 6 12 18 24 30 36 42
0
10
20
30
40
50
60
70
80
90
100
RT TMZ/RT
Median OS: 12.1 mos 14.6 mos
2-yr survival: 10% 26%
HR [95% CI]: 0.63 [0.52-0.75]
P<0.0001
TMZ/RT
RT
%
months
0000000000000000000000000000000000000000000000000000 6 12 18 24 30 36 42
000000000000000000000000000000000000000000000
10
20
30
40
50
60
70
80
90
100
RRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRT TTTTTTTTTTTTTTTTTTTTTTTTTTMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZ//////////////////////////////////RT
Mediaaaaaaaaaaaaaaaaaaaaaaaaaaaannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn OSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS::::::::::::::::::::::::: 12222222222222222222222222222222222222222222222222.11111111111111111111111111111111111111111111111111 mmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmoooooooooooooooooooooooooooooooooooooooooooooooooooooosssssssssssssssssssss 14.6 mos
2-yr suuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuurrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvviiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiivvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvalll::::::::::::::::::::::::::::::::::::::: 1111111111111111111111111111111111111111111111111000000000000000000000000000000000000000000000000000000%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% 26%
HRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRR [[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[[999999999999999999999999999999999999999999999999999999995555555555555555555555555555555555555555555555555555555%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCI]: 0.63 [0.52-0.75]
P<0.0001
TMZ/RT
RT
%
3
2.3
1.7
0
0.5
1
1.5
2
2.5
3
RT RT/CHEMO RT/Neut
Laramore GE, et al. Int J Radiat Oncol Biol Phy. 1989;17:1351-1356.
M
e
d
i
a
n

S
u
r
v
i
v
a
l

(
y
r
)

Shapiro W (BTCG) et al. J Neursurg 7:392-401, 2006.
GBM
AA
S
h
a
p
i
r
o

W

(
B
T
C
G
)

e
t

a
l
.

J

N
e
u
r
s
u
r
g

7
:
3
9
2
-
4
0
1
,

2
0
0
6
.

Why worse OS
Remember AA live long enough to
develop toxicity
IA worse toxicity
9.5% irreversible encephalopathy
15.5% ipsilateral vision loss
5% stroke
Shapiro W (BTCG) et al. J Neursurg 7:392-401, 2006.
Yung WKA, et al. J Clin Oncol. 1999;17:2762-2771.
EORTC
26053/22054
Schema
RT = 5940/33fx
Adjuv. TMZ to 12 mo in
responders
RT
Observation
Observation
Adjuvant TMZ
200mg/M2
5 D/28D
RT
+ TMZ
75mg/M2/D
100% response to chemotherapy with 1p 19q LOH.
*Ino Y, et al. Clin Cancer Res. 2001;17:839-845.
Cairncross G, et al. J Clin Oncol. 2006;24:2707-2714.
van den Bent MJ, et al. J Clin Oncol. 2006;24:2715-2722.
Results
RTOG 9402 EORTC 26951
Cairncross G, et al. J Clin Oncol. 2006;24:2707-2714.
van den Bent MJ, et al. J Clin Oncol. 2006;24:2715-2722.
Cairncross G, et al. J Clin Oncol. 2006;24:2707-2714.
Overall Survival
van den Bent MJ, et al. J Clin Oncol. 2006;24:2715-2722.
Results
Studies confirm importance of 1p 19q LOH
in prospective trials.
RTOG 9402 EORTC 26951
Overall Survival in Both Treatment
Arms with & without Combined 1p
19q Loss
Cairncross G, et al. J Clin Oncol. 2006;24:2707-2714.
van den Bent MJ, et al. J Clin Oncol. 2006;24:2715-2722.
Conclusions on AO Studies
NCCTG N0577: Intergroup Phase III 1p/19q
Co-deleted Anaplastic Oligodendroglioma
Newly
Diagnosed AO/
AO
1p/19q
co-deletion
RT (5960cGy)
TMZ x 12 cycles
RT + TMZ TMZ (Stupp)
N=245
N=24
5
N=50
Translational correlates
- 1p/19q translocation
- MGMT promotor methylation
- Neurocog/QOL
Primary endpoints:
- RT vs RT/TMZ: OS
- TMZ: Neurocog/Clin/MRI
Karim AB, et al. Int J Radiat Oncol Biol Phys. 1996;36:549-556.
45
Gy
59.4
Gy
P-value
5-yr
PFS
47% 50% 0.94
5-yr OS 58% 59% 0.73
LGG
n=203
Age
Grade
Histology
Resection
Tumor size
Institution
50.4 Gy*
64.8 Gy
*Focal fields: Tumor volume (by CT and/or MRI) + 2 cm margin to 50.4 Gy
Boost: Tumor volume + 1 cm margin
*Arm A: 50.4 Gy vs
Arm B: 64.8 Gy
Karim AB, et al. Int J Radiat Oncol Biol Phys. 2002;52:316-324.
Contro
l
RT P-value
5-yr
PFS
35% 55% <0.0001
5-yr OS 66% 68% 0.87
Van den Bent, et al. Lancet. 2005.
Van den Bent, et al. Lancet. 2005.
P
i
g
n
a
t
t
i

F
,

e
t

a
l
.

J

C
l
i
n

O
n
c
o
l
.

2
0
0
2
;
2
0
:
2
0
7
6
-
2
0
8
4

Low risk:Arm
1
Age <40 and
GTR
High risk:
Age >40 or
STR/
biopsy
Arm 2: RT
54 Gy
Arm 3: RT + 6
cycles PCV
~111 low risk
254 high risk
P60 mg/m
2

CCNU 110mg/m
2

VCR 1.4 mg/m
2

98-02: Survival by Arm
Shaw E, et al. JNS 109:835-841, 2008.
*Residual Tumor on MR: 59% <1cm , 32% 1-2 cm, 9% > 2 cm
*Shaw E, et al. JNS 109:835-841, 2008. 5 Yr PFS 70%* and 13%**
<4cm, oligo, <1cm imaging residual*
>4cm, astro, >1cm imaging residual**
Low risk:Arm
1
Age <40 and
GTR
High risk:
Age >40 or
STR/
biopsy
Arm 2: RT
54 Gy
Arm 3: RT + 6
cycles PCV
~111 low risk
254 high risk
P60 mg/m
2

CCNU 110mg/m
2

VCR 1.4 mg/m
2

251 high risk patients
2/3 enhancing and 2/3 O/OA
Originally compared survival data
Wilcoxan test
sensitive early separation of curves
Shaw E, et al. abstract #2006, oral presentation ASCO 2008.
PCV=Procarbazine, CCNU, vincristine
Exploratory compared Log Rank test
sensitive late separation of curves
Shaw E, et al. abstract #2006, oral presentation ASCO 2008.
PCV=Procarbazine, CCNU, vincristine
*Wilcoxan P-value OS = 0.33, PFS = 0.06
Shaw E, et al. abstract #2006, oral presentation ASCO 2008.
Ad hoc-Inclusion of only 2 year survivors-improved PFS + OS
Shaw E, et al. abstract #2006, oral presentation ASCO 2008.
*Low-risk arm big impact on practice
LGG
n=466
1p Status
etc.
50.4 Gy*
TMZ x 12
Focal RT daily 28 x 180 cGy
Total dose 50.4 Gy
Temozolomide 75 mg/m
2
po qd for 6 weeks,
then 150-200 mg/m
2
po qd day 1-5 q 28 days for 12 cycles
Concomitant
TMZ/RT
Adjuvant TMZ
Weeks 6 10 14 18 22 26 30
RT Alone
R
0
*Symptomatic = uncontrolled headaches or seizures, focal deficits, cognitive symptoms
E3F05 Phase III Symptomatic* or
Progressive LGG: RT +/-
Temozolomide
N= 540
S
u
r
v
i
v
a
l

S
u
r
v
i
v
a
l

Time (yrs)
GTR
STR
GTR
STR
GGTR
SSTR
SSTR
GGTR
CP1288306-14
P<0.0001
P=0.004
Radiation
Chemotherapy
Surgery
Tumor location and
progression
Medications
Nutritional
deficiency states
Retrospective trials neurocognitive decline in
adults
Outdated, primitive technique (whole brain
RT)
Large fraction sizes
Unknown denominator
Most important- LACK OF BASELINE
TESTING
NCCTG 86-72-51 corollary study
20 patients (10 Arm 50.4 Gy, 10 Arm 64.8
Gy)
Underwent extensive battery
neurocognitive tests* at baseline (after
surgery, before RT), and q18 months up
to 5 years
Neurocognitive Toxicity
No differences in neurocognitive function
between the two arms or compared to
baseline
Results consistent with other prospective
trials
tumor progression most important cause of
deterioration
Laack N, et al. Int J Radiat Biol Oncol Phys. 2005; 63:1361-7.
*Predominately at higher doses; **at 5 years; ***Decline in memory and
attention only if tumor progressed
Incorporation of chemotherapy
into treatment regimens
prospective trials needed
Support E3F05 (RT vs. RT + TMZ)
Modern, focal RT low risk
cognitive deficits
Brown et al., IJROBP 58 (4):1153-1160, 2004
O
v
e
r
a
l
l

s
u
r
v
i
v
a
l
,

%

Extent of resection image defined
Rogers (Barrow Neurologic Insitute) JNS 102:629-636, 2005. Median RT dose 54 Gy
*P=0.018 compare to GTR and P=0.003 compared to STR + RT
Authors recommend post-op RT for all patients due
to irregular shape, nerve root involvement of
Myxopapillary
Akyurek J Neuro-Onc 80:177-183, 2006. Median RT dose 50.4 Gy
*P<0.05
Pica, Miller, et al. IJROBP 74:11141120, 2009. Median RT dose 50.4 Gy
* P=0.4 compared to surgery alone **P=0.05 compared to surgery alone
Schild et al, IJROBP 53(3): 787, 2002. Mayo also found benefit >50 Gy
P<.001
P<0.01
Median OS Grade I NR Grade II 4.1 years
Grade III 1.6 years Grade IV 0.8 years
P=.04
P=.52
> 35 Gy
< 35 Gy
P=0.04
Pilocytic
CuLllne
lLulLarv Adenoma
vesubular Schwannoma
Menlnaloma
Cranlopharvnaloma
lLulLarv Adenoma
Lpldemloloav
8epresenL beLween 10-1S of all CnS
neoplasms
lemales>males (especlallv mlcroadenomas)
usuallv beLween aaes 4S-SS
8enlan, lnvaslve, or carclnoma
Ma[orlLv are benlan (areaLer Lhan 60)
lnvaslve adenomas make up 3S
1rue carclnomas are rare (<0.2)
Ceneuc
MLn 1-loss of funcuon of Lhls Lumor suppressor aenes
can cause Lumors ln paraLhvrold, pancreauc lsleLs, or
plLulLarv aland
Cs-alpha-an acuvauna muLauon of Lhe alpha subunlL of
Lhe auanlne nucleoude sumulaLorv proLeln found ln 40
of somaLoLroph adenomas
11C-plLulLarv Lumor Lransformlna aene ls over-
expressed ln mosL plLulLarv adenomas
lCl recepLor-4-A LruncaLed for of Lhe recepLor for
broblasL arowLh facLor-4 ldenued ln plLulLarv adenoma
AssoclaLed Svndromes
MLn-1
Carnev complex-rare lnherlLed condluon
wlLh spouv skln plamenLauon, mvxomas,
endocrlne over acuvlLv, and schwannomas
lsolaLed famlllal somaLoLroplnomas (llS)-Lwo
or more cases of acromeaalv ln a famllv ln Lhe
absence of MLn-1 or Carnev complex
Carnev Complex
AnaLomv
Mldllne sLrucLure slLuaLed ln Lhe sella Lurclca ln Lhe bodv of
Lhe sphenold bone
1he posLerlor lobe arlses as an lnvaalnauon from Lhe oor
of Lhe Lhlrd venLrlcle
1umors of Lhe poster|or |obe are v|rtua||y unknown
1he anLerlor and lnLermedlaLe lobes arlse from 8aLhke's
pouch as an lnvaalnauon from Lhe roof of Lhe nasopharvnx
1he anLerlor plLulLarv aland ls responslble for Lhe secreuon
of Lhe followlna hormones: C8P, 18P, CP-8P, CP-8lP
(somaLosLaun), lSP-8P, LP-8P, 8P, lP
1he normal aland welahs 0.6 arams
1Smm A bv 12 mm sup-lnf
Slze
Mlcroadenomas are <10mm
Ma[orlLv are mlcroadenomas
Macro adenomas >10 mm
ClanL adenoma > 40 mm
SecreLorv
70 SecreLorv
rolacunomas Lhe most common
30 non-secreLorv
ulerenual ulaanosls of Sellar
Leslons
lLulLarv adenoma
lLulLarv hvperplasla
Cranlopharvnaloma
Menlnaloma
Chordoma
Lvmphoma
Cerm cell Lumors
MeLasLasls
lnammaLorv
CvsLs (8aLhke's clef,
arachnold, dermold)
Pardv and vezlne Classlcauon (modled bv
Wllson)
Grade: Relationship of adenoma
to sella and sphenoid sinuses
Extrasellar extension
I: Sella normal or focally
expanded; tumor <10 mm
A: Occupying cistern
II: Sell enlarged; tumor >= 10
mm
B: Recesses of the 3
rd

ventricle
III: Localized perforation of
sellar floor
C: 3
rd
ventricle grossly
displaced
IV: Diffuse destruction of
sella floor
D: Intracranial (intradural)
V: Spread via CSF or blood E: Into or beneath cavernous
sinus
PlsLoloalc Classlcauon
lmmunocvLochemlcal sLalnlna correlaLes wlLh
hormone levels
20 have no ldenuable hormone producuon
ulLrasLrucLure crlLerla can conrm nonfuncuonal
leslons orlalnaLed from plLulLarv (Gn and
ro|acnnoma!)
CaLeaorlze cvLoloalcal dlerenuauon of Lumor
cells ln Lerms of dlerenL plLulLarv cell Lvpes
luncuonal CrlLerla
1. rolacunomas
2. AC1P-produclna adenomas (somaLoLrophs)
3. CP-produclna adenomas (somaLoLrophs)
4. 1SP-produclna adenomas (LhvroLrophs)
S. non funcuonlna adenomas (usuallv
aonadoLrophs)
aLholoav
CP and prolacun are derlved from subLvpes of
acldophlllc cells, whereas AC1P, 1SP, LP, and lSP
are secreLed bv dlerenL basophlllc cells).
Chromophoblc are non-secreuna however 8L mav
be lncreased due Lo compresslon.
kl-67 elevaLed
WPC uses lPC and secreLorv pauern (somaLoLroph,
lacLoLroph, aonadoLroph, corucoLroph, LhrvoLroph,
plurlhormonal, null-cell)
rolacunomas
>2S0 ua/L common (normal <1S ua/L)
SvmpLoms noL correlaLed wlLh level
Mlcroadenomas are found ln 11 of auLopsles
wlLh prolacunomas maklna up 44
Klibanski, A. NEJM. 262;13, April 1, 2010
8ouLes of Spread
Local lnvaslon/compresslon
lmplanLs ln subarachnold space and dura ls
rare
Work up
P& wlLh speclal auenuon Lo neuroloalc exam
lncludlna vlsual eld Lesuna
Lndocrlne workup
Serum prolacun, AC1P, lCl-1, CP, 24 Pr urlne free
corusol, dexameLhasone suppresslon LesL, serum LP/
lSP, Lhvrold funcuon, LesLosLerone, esLradlol
lor Lumors <10 mm ln an asvmpLomauc pauenL, conslder
[usL checklna prolacun levels
lmaalna
M8l wlLh Cad (plLulLarv proLocol), C1 for bone
desLrucuon, skull lms
roanosuc lacLors
1umor slze
LxLenL of endocrlne dvsfuncuon
Suprasellar exLenslon
Aae (vounaer ls beuer)
Cllnlcal resenLauon
Lndocrlne chanaes
Peadaches
8lLemporal hemlanopsla
CphLhalmopleala (Cn lll palsv)
Losls
ulplopla
laclal numbness
normone 5yndrome
AC1P nelson's svndrome, Cushlna's dlsease
CrowLh
Pormone
Acromeaalv, alaanusm
LP, lSP Cllnlcal svndromes uncommon: varlable
and lnemclenL hormone producuon
rolacun Amenorrhea, aalacLorrhea, lnferullLv,
lmpoLence
1SP PvperLhvroldlsm
Acromeaalv
Acromeaalv
Acromeaalv
Larae hands
Larae feeL
8row proLrude
!aw proLrude
Spaclna ln LeeLh wlden
Larae llver
Larae spleen
Larae kldnev
Larae hearL
Plaher rlsk of uM
Plaher rlsk of hearL dlsease
1reaLmenL
1reaLmenL
Medlcal ManaaemenL
8romocrlpune and caberaollne (a dopamlne aaonlsL) for
prolacun secreuna Lumors
Can reduce secreuon and slze ln 80
Can sLop afer 2 vears of normal hormones levels and close f/u
SomaLosLaun analoas (ocLreoude, lanreoude) for
arowLh hormone secreuna
S0-60 success raLe ln Lhose noL respondlna Lo suraerv
lor AC1P secreuna, mlLoLane, keLoconazole,
meLapvrone
usuallv less eecuve Lhan local Lheraples.
lndlcauons for 1herapv ln
rolacunomas
Macroadenoma
Lnlaralna mlcroadenoma
lnferullLv
8oLhersome aalacLorrhea
Cvnecomasua
1esLosLerone declencv
Cllaomenorrhea or amenorrhea
Acne and hlrsuusm
Suraerv
Allows prompL decompresslon of mass eecL
PlsLoloav
8apld normallzauon of hormone levels
Lona Lerm conLrol of 80-90 of
mlcroadenoma and 2S-S0 wlLh
macroadenomas
lndlcauons for Suraerv wlLh
rolacunomas
lncreaslna Lumor slze desplLe medlcal Lherapv
lLulLarv apoplexv
lnablllLv Lo LoleraLe dopamlne aaonlsL
roaresslon wlLh dopamlne aaonlsL
erslsLenL chlasmal compresslon
unresponslve cvsuc prolacunoma
women seeklna ferullLv, macroadenoma ln close proxlmlLv Lo
opuc chlasm desplLe opumal medlcal Lherapv (prepreanancv
debulklna recommended
CSl leak afer dopamlne aaonlsL
uopamlne aaonslsL conLralndlcaLed (psvchlaLrlc condluons)
Klibanski, A. NEJM. 262;13, April 1, 2010
1reaLmenL
Suralcal
1ranssphenoldal mlcrosuraerv ls parucularlv eecuve ln
removal of mlcroadenomas, buL also ls used for adenomas
LhaL exLend ouLslde of Lhe sella
ConLralndlcauons Lo Lranssphenoldal approach are
dumbbell-shaped adenomas wlLh consLrlcuon of Lhe
dlaphraam of Lhe sella, laLeral suprasellar exLenslon,
masslve suprasellar Lumors, and an lncompleLelv
pneumauzed sphenold
Cfen wlll sLarL prolacunomas wlLh medlcal manaaemenL
rsL
1rans-sphenoldal Suraerv
Courtesy of John Kuo, MD UW Neurosurgery
Problem: Approaching the sella
Modern trans-sphenoidal craniotomy
Minimally invasive technique
Microscope, endoscope visualization
Neuro-navigational guidance
Short hospital stay and quick recovery
70-90% of microadenomas are cured
60% of macroadenomas recur > 5 years
Low complication rate
Surgical complications (<10%)
CSF leak
Infection
Hemorrhage
Stroke
Pituitary dysfunction
Cranial neuropathies
<1% mortality for experienced surgeons
Trans-sphenoidal approach
Sagittal approach to the sella
Extended trans-sphenoidal approach
to the anterior skull base
Trans-sphenoidal clival approach
1rans-sphenoldal Suraerv
lndlcauons for x81
lncompleLe resecuon
8ecurrenL Lumors
lnoperable pauenLs
8efracLorv secreLorv Lumors
1reaLmenL
8adlauon
Cavernous slnus lnvaslon ls probablv noL
amenable Lo suraerv and ls beuer LreaLed wlLh
radlauon
L881 conLrols hvpersecreuon ln abouL 80 of
pauenLs wlLh acromeaalv, S0-80 of Lhose wlLh
Cushlna's dlsease, and abouL 1/3 of Lhose wlLh
hvperprolacunemla
Loca| contro| versus b|ochem|ca| contro|
1echnlque
1echnlques lnclude:
wedaed laLerals wlLh a coronal eld
movlna arc elds
360-dearee roLauonal elds
IMk1
5k5/I5k1
ln aeneral, Lhe porLals are SxS or 6x6 cm. use a plLulLarv board for 3uC.
lracuon slzes >2 Cv lncrease rlsk of chlasmal damaae.
Dose
4S Cv/1.8 Cv fx's for nonsecreuna mlcroadenomas
S0.4-S4 Cv/1.8 Cv fx's for macroadenomas or secreuna Lumors
Local conLrol non secreuna Lumors 90-100, CP secreuna 80-90,
AC1P secreuna 60-80, prolacunomas 80-90
Brada et al. Clinical Endo. 61(5):531-43. Nov 2004
S8S
llrsL used ln 1968 for plLulLarv adenoma
lndlcauons for S8S lnclude:
LxLenslon Lo cavernous slnus
Small (<4cm lnoperable Lumors)
lncompleLe suralcal exLrlpauon
8ecurrence afer L881
S8S
8everses endocrlnopaLhles fasLer and more
predlcLablv Lhan L881
Need to ho|d drug therapy before and dur|ng
5k5
uoses ranae beLween 12-28 Cv based on slze
and locauon. 88 suaaesL doses hlaher Lhan
1SCv lncrease LC for secreuna Lumors (Lrv Lo
achleve 20 Cv lf can be done safelv)
SecreLarv Lumors 24-28 Cv maralnal dose
non-secreLarv 14-16 Cv
Successful 1reaLmenL
8ased on resoluuon of svmpLoms
SLable dlsease Lo compleLe response
eak nadlr CP <1.0 a/L (Lwo-slLe assav) wlLh
oral alucose Lolerance LesL (CC11)
lCl-1 levels normal for aae and sex
Consensus statement, JCEM 89: 3099-3102, 2004
CuLcome-8adlosensluvlLv
1. CP
2. Cn8P
3. 1SP
4. AC1P
CuLcome
Study n technique Follow-up
Biochemical
response
LC
Mackley 2006
IJROBP
34 IMRT 42.5 m 100% 89%
Minigione 2006
Neurosurgery
100 SRS 45 m -- 92%
Collin 2005
IJROBP
110 Arc/FSRT 82 m 100% 89%
Pollock 2003
Neurosurgery
55 SRS 43 m -- 97%
Petrovich 2003
Neurosurgery
78 SRS 41 m -- 96%
Estrada1997
NEJM
30 3DC 42 m 83% 83%
AcuLe 1oxlclLv
lauaue
Cuus
Alopecla
Ccular hvpersensluvlLv
LaLe LecLs
up Lo 7S have CP declencv
S0 have declencv ln lSP, LP
1SP and AC1P or leasL llkelv Lo be aecLed
vascular ln[urv <S
Cpuc neuropaLhv (<2)
8adlauon necrosls (1)
Secondarv mallanancles (1)
neuropsvcholoalcal (1)
Brada M, et al. IJROBP 45:693-698, 1999
Becker G, et al. Strahlenther Onkol 178:173-186, 2002
Lndocrlne ueclLs afer S8S
8eLrospecuve revlew of 128 pLs underaolna
CkS aL Mavo Cllnlc
8lsk of anL plL declL was 16 and 4S aL 2
and S vears, respecuvelv
oor vlsuallzauon and mean dose Lo plLulLarv
predlcuve of endocrlnopaLhv
<7.S Cv, 0 (0/7): 7.6 Lo 13.2 Cv, 29 (7/24): 13.3
Lo 19.1 Cv, 39 (9/23): >19.1 Cv, 83 (S/6)
Leenstra et al. Neurosurgery. 67:27-33, 2010
lLulLarv vlsuallzauon
cotoool post-
ooJollolom 11-
welobteJ Mkls
sbowloo tbe votlobllltv
lo lJeoufvloo tbe
pltoltotv olooJ lo tbe
stoJv popolouoo. loot
vlsoollzouoo
of tbe pltoltotv olooJ
(leh). CooJ
vlsoollzouoo of tbe
pltoltotv
olooJ (tlobt).
Leenstra et al. Neurosurgery. 67:27-33, 2010
vesubular Schwannoma
lncldence
SvmpLomauc lncldence ls 1/100,000
Subcllnlcal ln 1/100
8epresenL 80-90 of CA Lumors
AlmosL alwavs unllaLeral
8llaLeral seen malnlv ln nl2 pauenLs
8lsk lacLors
Acousuc 1rauma
araLhvrold Adenoma
nl-2
1 ln 2Sk
Cell phones.conLroverslal
2 sLudles conLradlcLorv
robablv a lona laLenL perlod
aLholoav
uerlved from Schwann cell
Arlse from CbersLelner-8edllch zone
SLaln posluve for S100 proLeln
AnLonl A and 8 areas
AnLonl A and 8
naLural PlsLorv
varlable arowLh raLe
Ava 1.9 mm/vear
40 wlll show no arowLh or even sponLaneous
shrlnkaae on serlal lmaaes.
Cllnlcal resenLauon
SvmpLoms relaLed Lo Cn lnvolvemenL and local
proaresslon
Cllnlcal resenLauon
Acoustic
Nerve
Symptomatic involvement in
95%. Hearing loss, tinnitus.
Vestibular
Nerve
Involve 60% of patients. Mild to
moderate unsteadiness with gait.
Vertigo uncommon.
Trigeminal
Nerve
Occur in 15%. Facial numbness,
hypesthesia, and pain.
Facial Nerve 5%. Facial paresis and taste
disturbances.
Posterior
Fossa
Compression on cerebellum or
brainstem results in ataxia.
Acousuc neuromas usuallv arlse from Lhe cells of Lhe vlll nerve wlLhln Lhe lnLernal
audlLorv canal
Work-up
hvslcal exam
AudlomeLrv
lmaalna
ulaanosuc 1ools
Convenuonal
AudlomeLrv
Sensorlneural pauern
Cnlv 1/1000 pLs wlLh
hearlna asvmmeLrv wlll have
vS
ulaanosuc 1ools

Cadollnlum-enhanced
M8l
unlformlv enhanced
denslLv
Can expand Lhe lnLernal
audlLorv meaLus
CrowLh auern
Acousuc neuromas usuallv arow verv slowlv over a perlod of
manv vears (1-2mm/vear).
1he Lumor rsL dlsLorLs Lhe 8Lh nerve, Lhen presses on Lhe
ad[acenL 7Lh nerve. 1he 7Lh nerve ls araduallv sLreLched lnLo a
rlbbon llke sLrucLure over Lhe enlaralna Lumor
lL ls aL Lhls sLaae LhaL Lhe Lumor presses ad[acenL nerves llke
Lhe Lrlaemlnal responslble for faclal sensauon.
CrowLh auern
lnLracanallcular sLaae
Conned enurelv lnslde Lhe lnLernal audlLorv canal. Ls ofen
complaln of dlmculLv wlLh hearlna ln one ear, whlch mav bealn suddenlv
or lnsldlouslv. Pearlna loss mav be accompanled bv nolse lnslde Lhe ear
(unnlLus), dlzzlness and veruao.
LxLenslon ouL of lAC lnLo Lhe CA
1he Lumor has a characLerlsuc shape, wlLh a rooL llke
exLenslon ln Lhe lnLernal audlLorv canal and a alobular
poruon ln Lhe lnLracranlal cavlLv, [usL Louchlna Lhe
bralnsLem, cerebellum and some of Lhe cranlal nerves.
8ralnsLem compresslve sLaae
1he bralnsLem, cerebellum and cranlal nerves are belna
compressed bv Lhe Lumor. 1hls can lead Lo lncreased
headaches and numbness of Lhe face.
Pvdrocephalus or blockaae of CSl dralnaae
Can lead Lo severe svmpLoms such as double vlslon ,
dlmculLv wlLh speech and swallowlna, and even dlmculLv
wlLh breaLhlna, and evenLuallv deaLh
1reaLmenL Cpuons
Cbservauon
Suraerv
8adlauon
Cbservauon
AbouL 2S of cases are LreaLed medlcallv
Some Lumors arow onlv 1-2 mm / vear
Serlal audlomeLrv and M8l everv 6-12 monLhs
Mav be reasonable ln some pLs:
Llderlv pLs wlLh slow-arowlna Lumors conrmed on serlal
scans
Ls wlLh a leslon ln Lhe domlnanL or sole slde of hearlna
where an lnLervenuon would render hearlna loss
8lsks:
Pearlna loss desplLe mlnlmal arowLh
7S of Lumors arow wlLhln 1 vear
Suraerv
S0 of pauenLs are LreaLed suralcallv
SLeep learnlna curve (20-60 cases)
MorLallLv ~ 2
Cure raLes > 9S
reservauon of faclal nerve and hearlna ls aoal
lnuenced slanlcanLlv bv Lumor slze and approach
laclal nerve funcuon ls elecLrlcallv monlLored durlna
suraerv.
1hree Suralcal Approaches
1. 8eLromasLold subocclplLal rouLe
unllaLeral posLerlor fossa cranlecLomv
lor anv slze Lumor
AuempLs Lo preserve hearlna
1hree Suralcal Approaches
2. 1ranslabvrlnLhlne rouLe
lnclslon behlnd ear
8emoval of peLrous bone
used for Lumors >3cm or smaller Lumors where
hearlna preservauon ls noL aoal
1hree Suralcal Approaches
3. Mlddle fossa rouLe
lor small Lumors <1.S cm locaLed ln laLeral lAC
Maxlmum hearlna preservauon of suralcal
approaches
Pearlna preservauon abouL S0
Suraerv Compllcauons
osL-op compllcauons ~ 20
1. CSl leak - S-1S
2. Menlnalus - 2-10
3. laclal weakness - 4-1S
4. Pearlna loss varles accordlna Lo approach
S. Peadache - 10-34
6. SLroke
7. 8raln ln[urv
Mlcrosuraerv 8esulLs
Year #Pts LC FM HP Comp. Death
OJEMANN 1993 410 97% 96% 36% 10.5% 0.5%
HOUSE 1982 216 99.5% 83% 40% 10.6% 0.4%
HARDY 1989 100 97% 82% 16% 18% 3%
TOS 1988 300 87% 10.5% 2%
EBERSOLD 1992 256 97% 92% 49% 28% 0.7%
SCRIPPS 1994 11 91% 91% 18% 9% 0%
SAMII 1997 1000 98% 15% 20% 1.1%


AVERAGE 2293 98% 90% 27% 17% 1.1%
LC=Local control; FM=Facial movement; HP=Hearing preservation
1hree 8adlauon Approaches
1. SLereoLacuc 8adlosuraerv
Camma knlfe or Llnac 8ased
vlable opuon for pauenLs wlLh Lumors <3cm or
for arowlna Lumors ln medlcallv lnoperable
12.S Lo 13 Cv
1vplcallv prescrlbe Lo S0 luL wlLh CkS
1v ls macroscoplc volume seen on M8l
S vear lS correlaLed wlLh Lumor slze (1.S
decrease per 1 cm
3
)
noren eL al.
LaraesL slnale phvslclan experlence
669 pLs from 1969 Lo 1997
Lona-Lerm arowLh conLrol of 9S
laclal numbness/weakness . over time
(32% to 2%)
Pearlna preservauon 6S-70
Noren G et al. Stereotactic & Functional Neurosurgery. 70 Suppl 1:65-73, 1998 Oct.
unlverslLv of lusburah
190 pLs LreaLed wlLh radlosuraerv
1992 - 1997
Medlan followup ls 30 monLhs
1he maralnal 81 doses: 11-18 Cv (medlan 13 Cv)
1he maxlmum doses: 22 Lo 36 Cv (medlan 26 Cv)
1reaLmenL volumes: 0.1 Lo 33 cm
3
(medlan 2.7 cm
3
).
Flickinger JC. Et al. Journal of Neurosurgery. 94(1):1-6, 2001)
kesecnon-free surv|va| was dened as Lhe absence of
slanlcanL or susLalned Lumor arowLh noL requlrlna suraerv.
Neuro|mag|ng-determmed tumor contro| was dened as Lhe
absence of anv documenLed 1- Lo 2-mm chanae ln Lumor
dlameLer on M8 lmaaes (lncludlna Lemporarv chanaes
AcLuarlal raLes of developlna faclal numbness (Lrlaemlnal neuropaLhv) or faclal
weakness afer radlosuraerv for acousuc neuroma ln 190 pauenLs.
Comparlson of acLuarlal freedom from developlna faclal weakness (faclal neuropaLhv) afer
radlosuraerv for acousuc neuroma ln pauenLs who recelved maralnal Lumor doses of 13 Cv
or less compared wlLh Lhose who recelved doses of 14 Cv or more.
Pearlna preservauon was classled as anv LesLable speech dlscrlmlnauon remalnlna, servlceable
hearlna (Cardner-8oberLson Class l-ll) remalnlna, and preservauon of Lhe same Cardner-
8oberLson hearlna level
unlverslLv of lusburah
Accordlna Lo muluvarlaLe analvsls, lncreaslna
maralnal dose correlaLed wlLh lncreased
developmenL of faclal weakness (p = 0.0342) and
decreased preservauon of LesLable speech
dlscrlmlnauon (p = 0.0122).
Flickinger JC. Et al. Journal of Neurosurgery. 94(1):1-6, 2001)
osL 1reaLmenL lmaalna
nakamura P. eL al. Amerlcan !ournal of neuroradloloav. 21(8):1S40-6, 2000
Analvzed Lhe evoluuon of follow-up M8 lmaalna
ndlnas afer aamma knlfe radlosuraerv.
Chanaes ln Lumor volume and enhancemenL were
assessed on 341 follow-up M8 sLudles obLalned ln 78
of 86 consecuuve pauenLs
lollow-up M8 sLudles were obLalned beLween 10 and
63 monLhs (mean, 34 monLhs) afer LreaLmenL.
1umor conLrol raLe was 81.
Serlal axlal 12-welahLed lmaaes ln a S2-vear-old woman.
noLe Lhe hvperlnLenslLv ln Lhe ad[acenL braln ussue aL 6 monLhs and remarkable
lmprovemenL aL 10 monLhs.
Nakamura H. et al. American Journal of Neuroradiology. 21(8):1540-6, 2000
Serlal conLrasL-enhanced axlal 11-welahLed lmaaes (4S0/17/S) ln a S1-vear-old man.
noLe LhaL Lhe Lumor shows Lemporarv enlaraemenL wlLh LranslenL loss of conLrasL
enhancemenL 3 monLhs afer LreaLmenL.
1emporarv enlaraemenL (41)
Nakamura H. et al. American Journal of Neuroradiology. 21(8):1540-6, 2000
Serlal conLrasL-enhanced axlal 11-welahLed lmaaes ln a 2S-vear-old woman. noLe LhaL
Lhe Lumor shows no chanae ln slze wlLh LranslenL loss of conLrasL enhancemenL 6
monLhs afer LreaLmenL and Lhereafer Lhe Lumor shows conunuous rearesslon wlLh
recoverv of conLrasL enhancemenL.
no chanae or susLalned rearesslon (34)
Nakamura H. et al. American Journal of Neuroradiology. 21(8):1540-6, 2000
Serlal conLrasL-enhanced axlal 11-welahLed lmaaes ln a 64-vear-old woman show enlaraemenL of Lhe cvsuc
componenL and LranslenL loss of conLrasL enhancemenL ln Lhe solld componenL aL 3 monLhs: rearesslon of Lhe
cvsuc componenL, sllahL enlaraemenL and recoverv of conLrasL enhancemenL of Lhe solld componenL, and sllahL
rearesslon of Lhe overall Lumor aL 18 monLhs: furLher enlaraemenL of Lhe solld componenL, no chanae ln Lhe
cvsuc componenL, and rearesslon of Lhe overall Lumor aL 24 monLhs: and remarkable rearesslon of Lhe Lumor aL
S0 monLhs.
AlLernauna enlaraemenL and rearesslon (13)
Nakamura H. et al. American Journal of Neuroradiology. 21(8):1540-6, 2000
Concluslon
uvnamlc chanaes ln Lhe vesubular
schwannoma are seen on serlal follow-up M8
sLudles obLalned afer aamma knlfe
radlosuraerv.
An lncrease ln Lumor slze up Lo 2 vears afer
radlosuraerv ls llkelv Lo be followed bv
rearesslon
vS 8adlosuraerv
Author Year N LC V n VII n VIII n
Noren 1998 669 95% 38% 33% 65%
Flickinger 2001 190 97% 1% 3% 71%
Spiegelman 2001 40 98% 8% 71%
Prasad 2000 200 94% 2.5% 1.5% 40%
Miller 1999 42 95% 29% 38%
Miller 1999 40 100% 15% 8%
Foote 2001 149 93% 12% (5%) 10% (2%)
S8S vs.. Mlcrosuraerv: lrance
non 8andomlzed prospecuve serles uslna pre-
and posL- 8x quesuonnalres
Mlnlmum follow up 3 vears
CkS=97 pLs
Mlcrosuraerv 110 pLs
Regis et al. J Neurosurgery. 2002 Nov; 97(5):1091-100.
S8S vs. Mlcrosuraerv: lrance
Treatment CN VII
Motor
disturbance
CN V
Disturbance
Hearing
Pres
Functional
disturbance
Hosp
stay
Work
missed
Surgery 37% 29% 37.5% 39% 23 130
GK 0% 4% 70% 9% 3 7
Regis et al. J Neurosurgery. 2002 Nov; 97(5):1091-100.
S8S vs. Suraerv
rospecuve cohorL of 82 pauenLs wlLh
unllaLeral vS <3cm
Ck mean dose 12.2Cv Lo Lumor maraln
no dlerence ln Lumor conLrol (100 vs. 96)
Ck beuer faclal nerve preservauon (63 vs.
S)
Pollack et al. Neurosurgery. 2006 58(7) 77-85
1hree 8adloLherapv Cpuons
2. lracuonaLed SLereoLacuc 8adlosuraerv
S0-SS Cv ln 2S-30 fracuons
20-2S Cv ln 4-S fracuons
1vplcallv 80 lsodose llne
lS81
8oLh mlcrosuraerv and sLereoLacuc
radlosuraerv for vesubular schwannoma are
assoclaLed wlLh a relauvelv hlah lncldence of
sensorlneural hearlna loss and oLher cranlal
neuropaLhles.
A prospecuve Lrlal of fracuonaLed S8S was
underLaken ln an auempL Lo preserve hearlna
and mlnlmlze lncldenLal cranlal nerve ln[urv.
lS81-!ohn Popklns
8evlew of 12S pLs
14 pLs >3cm (30Cv ln 10fx)
111 pLs <3cm (2SCv ln S fx)
1umor conLrol 100
laclal weakness 0 aL 2vears
S6 pLs wlLh pre and posL audlomeLrv
18 lmproved hearlna
46 malnLalned hearlna
Williams, IJROBP 2002 Oct 1;54(2):500-4.
lS81
33 pauenLs wlLh vS were LreaLed wlLh 2100
cCv ln Lhree fracuons durlna a 24-hour perlod
uslna convenuonal frame-based llnear
acceleraLor radlosuraerv.
1he medlan Lumor dlameLer was 20 mm
(ranae, 7-42 mm).
Poen JC. et al. Neurosurgery. 1999 45(6):1299-305.)
lS81-SLanford Lxperlence
8asellne and follow-up evaluauons lncluded
audlomeLrv and conLrasL-enhanced maaneuc
resonance lmaalna
Lnd polnLs were Lumor proaresslon,
preservauon of servlceable hearlna, and
LreaLmenL-relaLed compllcauons.
Poen JC. et al. Neurosurgery. 1999 45(6):1299-305.)
lS81
Medlan fu lnLerval of 2 vears (ranae, 0.S-4.0 vr).
1umor rearesslon or sLablllzauon was documenLed ln
30 pauenLs (97) and Lumor proaresslon ln 1 (3).
llve pauenLs (16) developed Lrlaemlnal nerve ln[urv
aL a medlan of 6 monLhs (ranae, 4-12 mo) afer S8S:
Lwo of Lhese pauenLs had preexlsuna Lrlaemlnal
neuropaLhv.
Poen JC. et al. Neurosurgery. 1999 45(6):1299-305.)
lS81
Cne pauenL (3) developed faclal nerve ln[urv
(Pouse-8rackmann Class 3) 7 monLhs afer S8S.
reservauon of useful hearlna (Cardner-8oberLson
Class 1-2) was 77 aL 2 vears.
All pauenLs wlLh preLreaLmenL Cardner-8oberLson
Class 1 Lo 2 hearlna malnLalned servlceable (Class
1-3) hearlna as of Lhelr lasL follow-up examlnauon.
Poen JC. et al. Neurosurgery. 1999 45(6):1299-305.)
lS81
1hls sLudv demonsLraLes a hlah raLe of
hearlna preservauon and few LreaLmenL-
relaLed compllcauons amona a relauvelv hlah-
rlsk pauenL cohorL
(1umors >1S mm or nl-2).
Poen JC. et al. Neurosurgery. 1999 45(6):1299-305.)
lS81 vs. S8S: AmsLerdam
129 pLs wlLh Ans from '92-'99
seudorandomlzauon
uenLaLe pauenLs recelved 20 or 2SCv/Sfx
LdenLulous pLs recelved S8S 10Cv or 12.S Cv
Mean lu 33 monLhs
Meijer et al, IJROBP 2003. Aug; 56(5):1390-96)
lS81 vs. S8S: AmsLerdam
Treatment Tumor
Control
CN V
Preservation
CN VII
Preservation
Hearing
Preservation
SRS 100% 92% 93% 75%
FSRT 94% 98% 97% 61%
Meijer et al, IJROBP 2003. Aug; 56(5):1390-96)
lS81 vs. S8S:1! Lxperlence
8eLrospecuve revlew
n=69 Ck and S6 lS81 pauenLs
12Cv Ck vs. S0Cv/2Sfx
Treatment Tumor Control CN V
Preservation
CN VII
Preservation
Hearing
Preservation
SRS 98% 95% 98% 33%
FSRT 97% 93% 98% 81%
Andrews, IJROBP. 2001 Aug 1;50(5):1265-78
1hree 8adloLherapv Cpuons
3. roLons
now onlv used for non-servlceable hearlna
1umors <2 cm
13 cobalL Cv equlvalenL wlLh 160 Mev proLons
Cnlv 33 hearlna preservauon raLe
1umor conLrol 9S wlLh 90 Cn v and vll
preservauon
Concluslon
SLereoLacuc radloLherapv uslna a fracuonaLed
schedule provldes a beuer Lumor conLrol raLe
and a slmllar raLe of deLerlorauon for hearlna
levels compared Lo an observauon pollcv.
lnlual S81 mav be a reasonable alLernauve Lo a
walL-and-see pollcv.
ls 8evaclzumab a Came Chanaer?
8ackaround
vLCl ls a crlucal medlaLor of Lumor
analoaenesls and vessel permeablllLv
ueLecLed ln schwannoma and lncreased levels of
Lhese facLors correlaLe wlLh lncreased arowLh raLe
lncreased levels of vLCl and vLCl8-1 correlaLed
wlLh lncreased Lumor arowLh raLe
88 of 10 consecuuve pauenLs wlLh nl-2
assoclaLed vS LreaLed wlLh bevaclzumab
nl-2
Asthagiri, AR et al. Lancet 2009
nl-2
AuLosomal domlnanL muluple neoplasla
svndrome
8esulLs from muLauons on nl2 Lumor
suppressor aene on chromosome 22q
1 ln 2S,000
Schwannomas, menlnalomas, ependvmomas,
asLrocvLomas, and neurobromas
8esulLs
vLCl expressed ln 100 of pauenLs ln sLudv
Medlan besL response was 26 reducuon
4 of 7 wlLh hearlna response (3 were noL
evaluable)
Plotkin et al. NEJM. 261-4, 358-67 July 23, 2009
Baseline Characteristics of the Patients and
Outcomes after Treatment with Bevacizumab
Plotkin et al. NEJM. 261-4, 358-67 July 23, 2009
8esL 8adloaraphlc 8esponse Lo
8evaclzumab
*
*
*
*
*
Six of ten patients experienced
radiographic responses; four of six
remain smaller at 11-16 months
C
h
a
n
g
e

f
r
o
m

b
a
s
e
l
i
n
e

(
%
)

*
Plotkin et al. NEJM. 261-4, 358-67 July 23, 2009
81CC 1011: rauonale
ueslaned Lo conrm Lhe cllnlcal response raLe
of bevaclzumab ln a laraer cohorL of nl2
pauenLs LreaLed aL muluple cenLers (open-
label phase).
LxploraLorv alm ls Lo deLermlne Lhe durablllLv
of cllnlcal response (randomlzed
dlsconunuauon phase)
NF2 patients
with
progressive
VS who are
not good
candidates
for surgery
or radiation
Bevacizumab
5 mg/kg IV q
2 weeks
for 6 months
Response
evaluation
including
tumor volume
and
measurement
of word
recognition
score every 3
months
Clinical
response
Tumor volume
decrease by
20% compared
to baseline OR
word recognition
score above 95%
critical threshold
compared to
baseline
Stable disease
Changes in
tumor volume or
word recognition
score not
meeting criteria
for clinical
response or
progressive
disease
Progressive
disease
Tumor volume
increase by
20% compared
to baseline OR
word recognition
score below 95%
critical threshold
compared to
baseline
R
a
n
d
o
m
i
z
e
d
d
i
s
c
o
n
t
i
n
u
a
t
i
o
n
Maintenance
therapy
Bevacizumab 5
mg/kg every
month for 12
months
Observation
Off protocol
Response
evaluation
including tumor
volume and
measurement of
word recognition
score every 3
months
Open-label bevacizumab Randomized discontinuation
N = 40 adult subjects
Accrual = 3 per month
rlmarv endpolnL
rlmarv endpolnL ls cllnlcal response raLe, dened as
Ll1PL8 decrease ln LaraeL vS volume bv > 20 compared
wlLh basellne C8 lncrease ln word recoanluon score ln
aecLed ear above Lhe 9S crlucal Lhreshold afer 6
monLhs of LreaLmenL
WlLh 38 analvzable sub[ecLs, Lhe sLudv wlll have aL leasL
90 power Lo deLecL an lncrease ln response proporuon Lo
aL leasL 11 aL a slanlcance level of 0.0S, uslna a one-
slded blnomlal LesL.
Amona Lhe 38 analvzable pauenLs, lf we observe 2 or more
responders, we wlll re[ecL Lhe null hvpoLhesls
Secondarv endpolnL
Secondarv endpolnL wlll be cllnlcal fallure raLe
ln monLhs 7 Lo 18 of LreaLmenL (afer
randomzauon)
elLher radloaraphlc proaresslon ln Lhe LaraeL leslon
(dened as an lncrease ln vS volume bv > 20
compared wlLh Lhe Lumor volume aL 6 monLhs) or
proaresslve hearlna loss ln Lhe aecLed ear
(dened as a decrease ln word recoanluon score
below Lhe 9S crlucal Lhreshold compared wlLh
Lhe word recoanluon score aL 6 monLhs)
Men|ng|omas
Lp|dem|o|ogy
Second commonesL prlmarv braln Lumor
13-26 of all prlmarv lnLracranlal Lumors
lncldence ls abouL 6/100k
Mav be hlaher based on auLopsv serles (up Lo
2)
90 benlan
lrequencles and lncldence of Menlnalomas -
C818uS, 2000-2004
* Incidence rates are per 100,000 person-years and are age-adjusted to the 2000
US Standard Population
Courtesy of Carol Krucho et al.
Menlnaloma lncldence bv Cender and Aae
aL ulaanosls - C818uS, 2000-2004
Age-adjusted to the 2000 US Standard Population
8lsk lacLors
lemale
nl2 (1/2 wlll have menlnalomas)
lncreased rlsk wlLh breasL cancer
rlor radlauon (unea caplLus, acne, WWll
survlvors, x81)
Plaher doses hlaher lncldence and shorLer
laLencv
rlor menlnaloma
AnaLomv
Skull uura MaLer Arachnold
MaLer Subarachnold MaLer
la MaLer 8raln
1umors LhouahL Lo arlse from
mesodermal arachnold cap cells
1hese cells common ln lnLracranlal
dural venous slnuses, crlblform
plaLe, medlal mlddle cranlal fossa,
and cranlal and splnal nerve exlL
foramlna
resenLauon
Selzures (mosL common, 30-40)
lncreased lC svmpLoms (PA, n/v, eLc)
neuroloalc declLs (Cn declLs, hearlna loss
from CA menlnalomas, menLal sLaLus
chanaes, weakness)
CrowLh lacLors, 8ecepLors, and
Women
Mav lncrease durlna preanancv
lncreased ln women who use hormones
Lxpress proaesLerone, androaen, and esLroaen
alpha and beLa recepLors
AssoclaLed wlLh lvmphanalolelomvomaLosls
(LAM)
Lxpress pepude arowLh facLors llke lnsulln-llke
arowLh facLors l and ll, ulC, vLCl, and LCl.
roanosuc lacLors
Crade
LxLenL of suraerv
8raln lnvolvemenL
Larae Lumor volume
8ecurrence
Ml8-1 lndex (conLroverslal)
aLholoav
8enlan
Less Lhan 4 mlLoses per hlah powered eld
ALvplcal
4 or more mlLoses per hpf plus 3 of Lhe followlna:
lncreased cellularlLv, small cells wlLh hlah
nuclear:cvLoplasm rauo, promlnenL nucleoll,
unlnLerrupLed pauernless or sheeL-llke arowLh, or
focl of necrosls
Anaplasuc
Slmllar Lo aLvplcal, buL Lo a hlaher dearee
WPC Crade
Grade I 80-90%. Brain invasion rare.
Subtypes include: meningiothelial,
fibrous, transitional, psammomatous,
angiomatous, microcystic, secretory,
lymphoplasmactye-rich, metaplastic
Grade II 5-20%. Subtypes include: atypical,
chordoid, and clear cell.
Grade III 1-2%. Median survival < 2 years.
Subtypes: anaplastic, rhabdoid,
papillary
Mavo Cradlna SvsLem
Atypia 4 or more mitoses/10 HPF or 3 of the
following: brain invasion, sheeting,
macronuclei, small cell formation,
hypercellularity
Anaplasia 20 or more mitoses/10 HPFs or frank
anaplasia
A word abouL recurrenL Lumors
Cccaslonallv show hlsLoloalc proaresslon Lo a
hlaher arade
Allellc loss of chromosome 22 llkelv and earlv and
prlmarv evenL ln Lhe uparade
Loss of 14q common
Loss of oLher chromosomes ofen laLer ln
proaresslon (1p, 2p, 6q, 9q, 10q)
ulaanosls
M8l and C1 are suaaesuve buL hlsLoloav mav be
needed Lo make dlaanosls
uural based mass LhaL enhances brlahLlv and
homoaeneouslv wlLh conLrasL
Well demarcaLed
uural Lall
Surroundlna edema on 12
C1 for bonv lnvolvemenL and calclcauons
L1 mav have a role ln assesslna Lhe aaaresslveness
Imaging
Para-falcine
The most common tumor never
studied in a cooperative group trial
Cavernous Sinus
Olfactory Groove
Courtesy of Leland Rogers
ulerenual ulaanosls
Acousuc neuroma
Lvmphoma
MeLasLasls
Sarcoldosls
Weaener's CranulomaLosls
lnfecuons (18)
1reaLmenL
Cbservauon
Suraerv
8adlauon
8adlosuraerv
C8 ALL Cl 1PL A8CvL
Cbservauon
AsvmpLomauc
Slower arowLh
Calclcauons
Pomoaeneous enhancemenL
lso Lo hvpo-lnLense ad[acenL 12 slanal
8enlan
Nakamura et al, Neurosurgery. 53:62-71, 2003
McDermott et al, Brain Cancer, p333-364, 2002
Yano S et al, J Neurosurg. 105(4)538-43, 2006
Cbservauon
8eLrospecuve revlew of 1,434 pauenLs from
1989-2004
603 had asvmpLomauc leslons
Slze, arowLh over ume, appearance of
svmpLoms
S8 of Lhe asvmpLomauc leslons were
observed
roaresslon noLed ln 37, buL svmpLomauc
proaresslon ln onlv 16
Yano S et al, J Neurosurg. 105(4)538-43, 2006
Suraerv
Cross LoLal resecuon lf medlcallv operable
C18 aenerallv LhouahL Lo alve 90 8lS, buL
depends on Slmpson Crade
8ecommended for vounaer pauenLs wlLh
suralcallv accesslble leslons
Slmpson Crade
Grade 5 year
recurrence rate
I Removal of tumor bulk,
surrounding dura, involved
bone
10%
II Removal of tumor with
diathermy of involved dura
20%
III Small focus left in situ 30%
IV Macrosocopic residual disease 40%
V Simple decompression
Meningioma
RECURRENCE after GTR alone
Author n (GTR) Local Recurrence
Mirimanoff (MGH)
Stafford (Mayo)
Condra (U Florida)
Total:
145
465
175
785
5-year
7%
12%
7%
7-12%
10-year
20%
25%
20%
20-25%
15-year
32%
-
24%
24-32%
Mirimanoff et al, Neurosurg 62:18, 1985
Stafford et al, Mayo Clin Proc 73:936, 1998
Condra et al, IJROBP 39:427, 1997
*
Author Local Progression
Wara (UCSF)
Condra (U Florida)
Mirimanoff (MGH)
Stafford (Mayo)*
5-year
47%
47%
37%
39%
10-year
63%
60%
55%
61%
15-year
-
70%
91%
-
20-year
75%
-
-
-
Wara et al, Am J Roentgenol Ther Nucl Med 123:453, 1975
Stafford et al, Mayo Clin Proc 73:936, 1998
Condra et al, IJROBP 39:427, 1997
Mirimanoff et al, J Neurosurg 1985; 62: 18-24
Meningioma
PROGRESSION after STR alone
*581 pts 1978 -1988 (116 STR)
Only 10 had post-op RT
TOTAL: 37-47% 55-63% 70-91% 75%
*
8ecurrence 8aLe afer C18 +/- x81
88 of 108 aLvplcal menlnalomas afer C18
from '93 Lo '04
28 recurred afer C18: 8 pLs had ad[uvanL 81
and none of Lhese 8 had a recurrence
8A showed LhaL men wlLh mlLoses and
promlnenL nucleoll had a 70 chance of
recurrence
10 of Lhe 30 pauenLs LhaL recurred had
recurrence relaLed morLallLv
Aahl eL al. neruosuraerv 64(1):S6-60, !anuarv 2009.
Aahl eL al. neruosuraerv 64(1):S6-60, !anuarv 2009.
llCu8L 3 . kaplan-Meler analvsls showlna Lhe percenLaae of aross LoLallv
resecLed AMs wlLh radloaraphlc recurrence versus ume afer resecuon ln vears
for Lumors LhaL recelved posLoperauve radlauon (n = 8) and Lhose LhaL dld noL
recelve posLoperauve radlauon (n = 100). Cox rearesslon analvsls revealed Lhe
dlerence beLween radlaLed and nonlrradlaLed cases Lo be noL qulLe sLausucallv
slanlcanL ( = 0.1).
Meningioma
ATYPICAL
Pearson B. et al. Neurosurg Focus 2008;24(5):E3
University of Alabama at Birmingham Reviewed 440 surgery pts
Grade 2 diagnosis 77 pts
Post-op RT (GK or EBRT)
GTR (Simpson 1-2) 25%
STR (Simpson 3-4) 76%
Med f/u (no RT) 28.2 mo
Local Failure
w/o RT 9% *
w/ RT 0%
* Excludes pts for whom RT was
recommended but not received.
Thus 6 Recurrences
Mean time to recur 17.7 mo
Mean f/u, no RT group, 28.8 mo
1 was grade 3 at recur, another was
rendered blind in 1 eye by recurrence
1994-99 2000 2001 2002 2003 2004 2005 2006
Year
50%
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
p=.001 (1994-99 vs 2006)
4.4%
32.7%
35.5% 35%
8adlauon
lndlcauons
SubLoLal resecuon
unresecLable Lumor
Plah arade
8ecurrenL
8adlauon
Crade 1
S0.4 Lo S4 Cv aL 1.8 Lo 2 Cv fracuons (1-2 cm
maraln)
Crade 2
S4 Lo S9.4 Cv aL 1.8 Lo 2 Cv fracuons (2-3 cm
maraln)
Crade 3
S9.4 Lo 60 Cv aL 1.8 Lo 2 Cv fracuons (2-3 cm
maraln)
8adlosuraerv
LxcellenL ouLcomes wlLh S8S for pauenLs wlLh
1umors <3S mm
<1Scc volume (<7.S cc even beuer)
no randomlzed daLa comparlna S8S wlLh
suraerv, buL for small leslons, Lhe resulLs
appear Lo be slmllar
Pollock, Stafford et al. IJROBP 2003; 55: 1000 - 1005
Kondziolka et al. Neurosurgery 1998; 43: 405 - 414
5y PFS, SRS Surg, WHO Grade 1 (often presumptive)
a
cavernous sinus *
Author Year n f/u (mo) No Histo Volume Margin Dose 5y-PFS
Chang 1997 55 48 7.3 cc 18 Gy 98% (med f/u 48mo)
Hakim 1998 127 31 54% 4.1cc 15 Gy 89%
Chang 1998 24 46 6.8cc 17.7 Gy 100% (med f/u 46 mo)
Liscak
a
1999 53 19 64% 7.8cc 12 Gy 100% (med f/u 19 mo)
Kondziolka 1999 99 43% 16 Gy 93%
Morita 1999 88 35 44% 10 cc 16 Gy 95%
Roche
a
2000 80 31 63% 5.8 cc 14 Gy 93%
Stafford 2001 168 41% 8.2 cc 16 Gy 93%
Shin
a
2001 15 42 30% 4.3 cc 10-12 Gy 75% (5 & 10y)
22 14-18 Gy 100% (5 & 10y)

Nicolato 2002 111 48 50% 8.4 cc 15 Gy 96%
Lee
a
2002 159 35 52% 6.5 cc 13 Gy 93% (97% if SRS sole tx)
Spiegelmann
a
2002 42 36 8.2 cc 14 Gy 97.5%
Pollock 2003 62 64 46% 7.4 cc
(All <35mm)
17.7 Gy 95% (7y) =Simpson 1
Roche 2003 32 56 75% 13 Gy 100% (med f/u 56 mo)
Iwai
a
2003 42 49 48% 14.7 cc
(>4cc SRSx2)
11 Gy 92%
Flickinger 2003 219 29 100% 5.0 cc 14 Gy 93% (at 5 and 10 yrs)
Chuang 2004 43 75 48% 5.7 cc 16 Gy 90% 7y (100% SRS sole tx)
Zachenhofer 2006 36 103 31% 20mm med dia 16.8 Gy (med) 94% (at 5 and 8 yr)
Combined: 1477 19-103 30-100% 4.1-14.7 10-18Gy 75-100%
14Gy 89-100%
Courtesy of Leland Rogers
SvsLemlc Lherapv for recurrenL
dlsease
LlmlLed daLa
MlfeprlsLone-proaesLerone and alucocorucold
recepLor anLaaonlsL
Pvdroxvurea-lnduces apopLosls and lnhlblLs cell
arowLh ln culLure
lnLerferon alpha 2b-lnhlblLs arowLh of
menlnaloma cells exposed Lo mlLouc sumull
Schrell et al. J Neurosurg. 86(5): 845-52. May 1997
Kiode. J Reprod Med. 43(7): 551-60. Jul 1998
Chamberlain et al. Cancer. 113(8):2146-51. Oct 2008
Cn Colna 1rlals
LC81C 26021-22021
hase lll randomlzed sLudv of ad[uvanL convenuonal
fracuonaLed radloLherapv or radlosuraerv versus
observauon onlv ln pauenLs wlLh newlv dlaanosed,
lncompleLelv resecLed, benlan lnLracranlal arade 1
menlnaloma
l !ohn Wolbers (n=478)
81CC - 0S39 (acuvaLed !une 2009)
hase ll sLudv of observauon for low-rlsk menlnalomas and
of radloLherapv for lnLermedlaLe and hlah rlsk
menlnalomas
l Leland 8oaers
RTOG - 0539 Schema
Group 1 (Low Risk): New Grade 1, GTR or STR
Group 2 (Interm Risk): Recurrent Grade 1, GTR or STR
New Grade 2, GTR
Group 3 (High Risk): Any Grade 3
Recurrent Grade 2
New Grade 2, STR
N=165
3D CRT or IMRT 54 Gy / 30 fxs Strata
Observation
Group 1
Group 2
Group 3
IMRT 60 Gy / 30 fxs
Opened June 19, 2009
Required Sample Size: 165
55 for each Group
Group 1 closed to accrual
on Sept 29, 2010
RTOG - 0539
Primary: 3-year progression-free survival
Secondary:
Histopathologic concordance, parent vs central
- diagnosis, grade, subtype
Incidence of grade 2+ acute and late adverse events
- Groups II and III, who receive RT, analyzed separately
Histopathologic correlates of progression-free survival
- light microscopy, immunohistochemical, and microarray
MRI Imaging correlates via central imaging review
- at diagnosis, at any failure, and at 3-yrs
Molecular correlative studies
- FISH: 1p, 14q, p16 region (CDKN2A) on 9p21
- IHC: MIB-1, PR, NDRG2
- Serum: HGF/SF, EGF, IGF VEGF
- Urine: VEGF MMP levels and dynamic trend
Adherence to protocol-specific target and normal
tissue IMRT parameters
Overall survival at 3-years
OBJECTIVES
Cranlopharvnaloma
Lpldemloloav
8enlan Lumor arlslna from remnanL of
8aLhke's pouch
1-3 of all lnLracranlal Lumors
10 of peds
8lomodal dlsLrlbuuon
Chlldhood S-14 vears
AdulL SS-6S vears
Male = lemale
no rlsk facLors
PlsLoloav
Adam"anunomaLous
Squamous paplllarv
Mlxed
1hese are benlan Lumors buL locallv can be
exLenslve.
AdamanunomaLous
6S of adulLs and 9S of chlldren
CrlalnaLe from ecLoplc remnanLs of 8aLhke's
pouch
Plah llpld/cholesLerol conLenL: crank case oll"
Calclcauons
Squamous aplllarv
AlmosL alwavs ln adulLs
Less llkelv Lo have cvsuc componenL
8arelv calcled
Some belleve lL has a beuer proanosls
Locauon
usuallv suprasellar arlslna ln plLulLarv sLalk
AnaLomlc classlcauon
rechlasmauc
8eLrochlasmauc
Subchlasmauc
LaLerallv expanslle
resenLauon
PA (S0)
n/v (3S)
apllledema (2S-40)
vlslon chanaes (40-70)
8lLemporal hemlanopsla
Pormonal chanaes secondarv Lo plLulLarv
hvpofuncuon
Lu ln men and amenorrhea ln women for 90 of
adulLs
Cverall 80 wlLh endocrlne abnormallues
Work up
P&
Pormone levels
LlecLrolvLes
uA/urlne lvLes
C1/M8l
lmaalna
laln lms: enlaraed dlsLorLed sella:
calclcauons
C1: paruallv cvsuc, low denslLv, conLrasL
enhanclna leslon wlLh calcs
M8l: Solld componenL lsolnLense on 12 buL
enhances wlLh aadollnlum. Cvsuc componenL
hvperlnLense Lo CSl on 12 and hvpolnLense on
11: cvsL rlm enhances wlLh aadollnlum
ulerenual ulaanosls
Menlnalomas
lLulLarv adenoma
MeLasLasls
Cpuc allomas
1eraLomas
SvsLemlc hlsuocvLosls
Sarcoldosls
laln lms wlLh suprasellar
calclcauons
1reaLmenL-Suraerv
uecompresslon vla venLrlculosLomv or v
shunL: uraenL decompresslve resecuon lf
acuLe vlsual deLerlorauon
ulaanosls
8esecuon lf small Lumor where C18 posslble
wlLhouL much morbldlLv
1reaLmenL: Suraerv
C18 mosL llkelv for
<3cm
re or lnLrachlasmaucleslons
Solld componenL
8eLrochlasmauc Lumors have hlaher morLallLv
wlLh sx
1rans-sphenold approach alves hlaher C18
10 vr LC wlLh C18=90, S18=30
1reaLmenL: Suraerv
Cfen dlmculL Lo resecL because of Lhe cvsuc naLure
Conslderable morbldlLv wlLh non-Lrlvlal operauve morLallLv
(as hlah as 20 ln older serles)
Lona-Lerm neuroloalc, endocrlne, and ophLhalmlc
compllcauons
Cfen suraeons wlll oer less aaaresslve suraerv followed
bv x81
10 vear survlval >90 wlLh abouL 90 local conLrol for S18
resecLed Lumors followed bv radlauon
Fahlbusch et al. J Neurosurg. 90(2):237-50. Feb 1999.
1reaLmenL: Suraerv81
8ecurrence afer S18 abouL S0
8lchmond serles
S18 vs. S18 + 81 reduced recurrence from 37 Lo 4 aL S vears
Welss serles
S18 vs. S18 + 81 reduced recurrence from 60 Lo 13 aL S vrs
karavlLakl serles
S1S vs. S18 + 81 reduced recurrence from 62 Lo 23
Modern serles suaaesL a local recurrence afer Sx and 81 Lo be less Lhan
10
Richmond et al. Neurosurgery. 6(5):513-17. 1980
Weiss et al. IJROBP. 17(6):1313-21
Karavitaki et al. Clin Endocrinol. 62(4):397-409. Apr 2005
Mark et al. Radiology. 197(1):195-8. Oct 1995
1reaLmenL: 8adlauon
used for lnoperable, parual resecuon, or
recurrenL dlsease
3uC, lS81, S8S, lnLracavlLarv brachvLherapv
>S4 Cv recommended. uoses >61 Cv wlLh
lncreased LoxlclLv
Regine et al. IJROBP. 24(4):611-7.1992
Habrand et al. IJROBP. 44(2):255-63. May 1999
Cavazzuti et al. J Neurosurg. 59(3):409-17. 1983
1reaLmenL volume
C1v = C1v + 1 cm.
1v = 3-Smm + C1v
1oxlclLv afer S18 + x81
Deficiency ADH Growth
Hormone
Thyroid
Hormone
Sex
Hormone
Steroids
Pre
Treatment
19% 30% 10% 12% 11%
Post
Treatment
25% 41% 66% 39% 59%
Cpnc neuropathy rare |f dose <60Gy and <2.5 Gy
per fx
nypotha|am|c obes|ty as h|gh as 50
Rajan et al, IJROBP 1997; 37:517-21
Flickinger et al. IJROBP, 1990; 9:117-22.
S8S
1reaL C1v onlv
uoses ranae beLween 11-20Cv based on slze
and locauon
chlasm < 8Cv
8ralnsLem <14Cv
Maraln dose musL be hlaher Lhan 6Cv
CuLcomes
S18 + x81 84 LC lf >S4Cv used
78 20 vear CS for Lhose LreaLed for prlmarv
dlsease versus 2S for recurrence
Regine et al. IJROBP 1992; 24:611-17.
1reaLmenL: CvsL ManaaemenL
Can be resecLed or scerlosed wlLh
chemoLherapv or radlo-lsoLope lnfuslon
8ecurrenL cvsLs mav requlre asplrauon and
placlna an Cmmava
Cvsuc 1umors

32
Lo a dose of 189-2S0 Cv has been used
90 S vr CS
70 LC aL 10 vears
8lsk of lnLracavlLarv soluuon leaks
Paseaawa eL al. neurosuraerv 2004: S4(4):813-20: 820-2