Less then 1 cm tumour / no hearing impairment - Observation - Yearly MRI scan & audiometry

1. Acoustic schwannoma/ neuroma
Less then 1 cm tumour / no hearing impairment
- Observation
- Yearly MRI scan & audiometry
Early small tumor: (size <2.5 cm)
- Hearing function present: Radiosurgery
- Hearing function not present: Radiosurgery or surgery
Larger tumour (>3.5 cm) / brainstem compression
- Facial Nr preservation not possible: Surgery
- Facial Nr Preservation possible: Surgery only with complication
Safe Surgery + radiosurgery
- Surgery not possible: Fractionated radiotherapy

2. Stage I: IAC fill
Stage II: Protrude through opening of IAC on the brain
Stage III: Growth comes in contact with brainstem
Stage IV: brainstem compression
AN: Koos Classification

3. Prospective studies: >100
Total number of patient treated with RS: >10,000
Follow up period: ≈20 yrs
In AN <2.5 cm treated with SRS,
PFS at 20 years – 95-98%
Facial Nr palsy – 0.5%
Symptomatic Progression – 2-3%
Severe toxicity – 0.1%

4. AN: Radiosurgery – Early studies
Higher dose; lower hearing function preservation
Preservation rate (%)
Author (yr) FU
(mo)
n Vol
(cc)
Marginal
dose (Gy)
Local
control (%)
CN V CN VII Hearing
Leksell (1971) 44.4 160 <3 cm 18-25 81 82 86 20
Flickinger
(1993)
24 134 2.57 12-20 89.2 67.1 71 35
Foote (1995) 16 36 3.14 16-20 100 41.4 33.5 41.7
Mendenhall
(1996)
>12 56 - 10-22.5 95 78.6 78.6 NA
Kondziolka
(1998)
>60 162 2.2 cm 16.6 98 73 73 51
Suh (2000) 49 29 2.1 8-24 94 85 68 26

5. AN: Radiosurgery – Dose <13 Gy, long term FU
Author (yr) n FU (yr) Vol
(cc)
Median
Dose (Gy)
Local
control (%)
CN V CN VII Hearing
Prasad (2000) 153 4.27 2.6 13 92 98.3 98.4 58
Unger (2002) 100 6.3 3.4 13 96 100 98 55
Chopra (2007) 216 5.7 1.3 13 93 96 94 68
Hasegawa (2005) 317 >5 - 12 93 100 94 60
Myrseth (2005) 103 >4 - 12.5 93 - 98.3 33.3
Kim (2007) 59 6 3.4 12 93 - 98.3 32
Iwai (2008) 25 7.4 0.27 12 100 100 100 64
Niranjan (2008) 96 3.5 - 13 99 100 100 64.5
Fukuoka (2009) 152 >5 2 12 94 97.4 100 64.5
Murphy (2010) 103 3.6 1.95 13 91.5 92 95 55
Combs (2006) 26 9 2.2 12.5 99 99.3 99.3 NA
Friedman (2006) 295 3.3 1.5 13 91 92 95 55
Kalogeridi (2009) 19 4.6 11 13 99.3 99.3 99.3 NA
Lower dose; Higher hearing function preservation; less toxicity

6. Enlargement of tumour after radiosurgery?
Post-SRS transient enlargement of tumour occurs
Due to radiation effect on tumour and replacement with granulation tissue
Subsides/ regress after 1.5 to 2 yr
Kapoor S et al; IJROBP 2010

7. Kondziolka et al NEJM 1998
Prospective evaluation of AN pts (n=162)
Regression of tumour in majority of pts
Regression is slow & occurs over years

8. MarginalDose(Gy)
Year
7-45 Gy
20 Gy
15 Gy
12 Gy
Local control maintained (>95% at 10 years)
Toxicities have come down
Hearing preservation increased
RT dose (Gy) Complication
rate (%)
10-12.5 13
15-17.5
(TV<5.5 cm3
)
9
15-17.5
(TV>5.5 cm3
)
71
20-22.5 100
Dose reduction have reduced toxicity
without compromise on local control
Mendenhal et al 2000

9. Hydrocephalus
Vertigo/ tinnitus
Cranial Nr Palsy
Complications depends upon
dosage schedule

10. Surgery possible after SRS ?
After SRS only few patients progress, they need surgery
SRS causes regression of blood supply, hence should be easy for resection
In a study, 8/13 pts with progression after SRS had difficult surgery !!
No clear contraindication of surgery after RS
Pollock et al; J Neurosurg 1998

11. Higher risk of second malignancy after SRS ?
After radiosurgery risk of second malignancy is very low
No report of any second malignancy after 7500 AN pt treatment in 18 yrs
Estimated risk 1: 1000 (0.001%)
Only two reported case of second malignancy
1. In Japan 4 yrs after surgery
2. Temporal lobe GBM 7.5 yrs after radiosurgery
Kondziolka et al 2000

12. AN: Radiotherapy – Long-term follow up (>10 yrs)
Local control: 95-98%; Hearing function preservation: 70-80%
Author (yr) n FU (mo) Vol (cc) Median
Dose (Gy)
LC (%) CN V CN VII Hearing
Kalapurakal (1999) 19 54 3.5 cm 36/6# 100 100 100 100
Fuss (2000) 51 42 8.6 57.6/30# 100 95.2 100 85
Meijer (2003) 80 33 2.5 cm 25/5# 94 98 97 61
Sawamura (2003) 101 45 1.9 cm 50/25# 91.4 96 100 71
Selch (2004) 48 36 2.5 54/30# 100 97.8 97.9 93
Chan (2005) 70 45.3 2.4 54/30# 100 96 99 84
Lin (2005) 16 48 1.75 cm 54/30# NA NA NA 90
Combs (2005) 106 48.5 3.9 57.6/30# 96.6 96.6 97.7 94
Koh (2007) 60 31.9 4.9 50/25# 100 100 100 77.3
Thomas (2007) 34 36.5 1 45/25# 100 100 94 63

13. Comparative study: Fractionated RT Vs SRS
Author (yr) RT type n FU (mo) Dose
(Gy)
LC (%) CN V CN VII Hearing
Andrews
Philadelphia
(2001)
FSRT 56 115 Wk 50/25# 97 93 98 81
SRS 69 115 Wk 12 98 95 98 33
Combs
Hiedelburg
(2010)
FSRT 172 75 mo 57.6/33# 96 97 98 78
SRS 19 75 mo <13Gy 96 100 95 78
SRS 11 75 mo >13Gy 96 93 88 NA
Kopp
Germany (2011)
FSRT 47 32.1 54/30# 97.9 NA 100 79
SRS 68 30.1 12 98.5 NA 100 85
Collen
Belgium (2011)
FSRT 78 62 50/25# 95 NA 88 68
SRS 41 62 12.5 95 NA 88 59
No difference in local control, hearing preservation & toxicity profile

14. Fractionated RT Vs SRS (n=202)
Local Control: FSRT vs SRS ( FU= 75 mo)
Coumb et al IJROBP 2000
FSRT vs SRS: No difference in local control

15. FSRT vs SRS <13 Gy dose
Coumb et al IJROBP 2000
FSRT vs SRS: No difference in hearing function preservation
Hearing function preservation

16. CLINICAL INVESTIGATION
LONG-TERM OUTCOMES OF VESTIBULAR SCHWANNOMAS TREATED
WITH FRACTIONATED STEREOTACTIC RADIOTHERAPY:
AN INSTITUTIONAL EXPERIENCE
SUMIT KAPOOR, M.B.B.S., M.P.H.,* SACHIN BATRA, M.B.B.S., M.P.H.,* KATHRYN CARSON, SC.M.,y
JOHN SHUCK, B.A.,* SIDDHARTH KHARKAR, M.B.B.S., M.H.S.,* RAHUL GANDHI,*
JUAN JACKSON, C.M.D.,z
JAN WEMMER, C.R.N.P.,z
STEPHANIE TEREZAKIS, M.D.,z
ORI SHOKEK, M.D.,z
LAWRENCE KLEINBERG, M.D.,z
AND DANIELE RIGAMONTI, M.D.*
Departmentsof *Neurosurgery and z
Radiation Oncology, JohnsHopkins Hospital, Baltimore, MD; and y
Department of Epidemiology,
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Purpose: We assessed clinical outcome and long-term tumor control after fractionated stereotactic radiotherapy
(FSRT) for unilateral schwannoma.
Methods and Materials: Between 1995 and 2007, 496 patients were treated with fractionated stereotactic radio-
therapy at Johns Hopkins Hospital (Baltimor e, MD); 385 patients had radiologic follow-up that met the inclusion
criteria. The primary endpoint was treatment failure. Secondary endpoints were radiologic progression and clin-
ical outcome. Logistic regression analysis assessed the association of age, race, tumor side, sex, and pretreatment
symptoms.
Results: In 11patients(3%) treatment failed, and they required salvage(microsurgical) treatment. Radiologic pro-
gression was observed in 116 patients (30.0%), including 35 patients (9%) in whom the treatment volume more
than doubled during the follow-up period, although none required surgical resection. Tumors with baseline vol-
umesof lessthan 1 cm3
were18.02 timesmorelikely to progressthan thosewith tumor volumesof 1cm3
or greater
(odds ratio, 18.02; 95% confidence interval, 4.25–76.32). Treatment-induced neurologic morbidity included 8 pa-
tients(1.6%) with new facial weakness, 12 patients(2.8%) with new trigeminal paresthesias, 4patients(0.9%) with
hydrocephalus (1 communicating and 3 obstructive), and 2 patients (0.5%) with possibly radiation-induced neo-
plasia.
Conclusions: Although the rate of treatment failure islow (3%), careful follow-up shows that radiologic progres-
sion occurs frequently. When reporting outcome, the ‘‘no salvage surgery needed’’ and ‘‘no additional treatment
needed’’ criteria for treatment success need to be complemented by the radiologic data. Ó 2010 Elsevier Inc.
Vestibular schwannoma, Fractionated stereotactic radiotherapy, Tumor progression, Clinical outcomes.
N=496
Median FU= 52 mo
Range= 5-138 mo
Salvage surgery= 11 (3%)
Radiological progression: 30%
Vol doubled: 9%
Facial weakness: 1.6%
Trigimenal: 2.8%
Hydrocephalus: 0.9%
RT dose:
25Gy/5#: 76% pt
30Gy/10#: 24% pt

17. Larger volume tumour treated with high dose have radiological progression
Radiological progression with fSRT

18. Gender (M:F) 7:9
Age Median (range) (yrs) 51(19-74)
Side (R:L:BL) 9:21:2
Pre-SRS hearing function
Serviceable HL 20 (63%)
Non-Serviceable HL 12 (37%)
Pre-SRS facial function status
H-B Scale I 22(69%)
H-B Scale II 3 (9%)
H-B Scale III 5 (15%)
H-B Scale IV -
H-B Scale V 2 (7%)
SRS Technique
Frameless
Framebased
19 (59%)
13 (41%)
Dose Median (range) (Gy) 14 (12-26.2)
FU Median (range) (mo) 6.5 (6-8)
ASH Experience: (n=32)
Balaji, Mahadev, Dutta et al, AROICON 2011
N=32
CyberKnife: 19 pt
BrainLAB: 13 pt
Serviceable hearing function : 20 pt
N=32
CyberKnife: 19 pt
BrainLAB: 13 pt
Serviceable hearing function : 20 pt

19. Grade PT ave (dB)
Grade I (good-
excellent)
0-30
Grade II (serviceable) 31-50
Grade III (non-serviceable) 51-90
Grade IV (poor) 91-max
Grade V (none) Not testable
Hearing function assessment
Gardner Robertson Scale
Gardner G, Robertson JH (1988 )Hearing preservation in unilateral acoustic
neuroma surgery. Ann Otol Rhinol Laryngol 97: 55–66.
Objective assessment of auditory function

20. Grade Description Measurement Function %
I Normal 8/8 100
II Slight 7/8 76 - 99
III Moderate 5/8 - 6/8 51 - 75
IV
Moderately
Severe
3/8 - 4/8 26 - 50
V Severe 1/8 - 2/8 1 – 25
VI Total 0/8 0
House Brackman Scale
"Measurement" is determined by measuring the superior movement of mid-portion of the superior
eye brow and the lateral movement of oral commissure. A scale point of 1 is assigned for each
0.25 cm of motion up to 1 cm for both eye brow and commissure movement.
The points are then added together.
Facial function assessment

21. Post-SRS
Pre SRS
Total**
I II III IV
I 3 0 0 0 3
II 4 6 0 0 10
III 1 6 5 0 12
IV 0 0 6 1 7
TOTAL* 8 12 11 1 32
*Total number of pts with corresponding GR scale in column pre-SRS;
** Total number of pts with corresponding GR scale in the row post-SRS;
Group of pts, hearing improved or remained within 20-dB considered hearing preservation
Gardner Robertson scale: Hearing function
Pre & post-SRS (6 month) evaluation
(n=32)

22. Post-
SRS
Pre-SRS
Total**
I II III IV V
I 21 0 0 0 0 21
II 1 2 0 0 0 3
III 0 2 4 0 0 6
IV 0 0 0 0 0 0
V 0 0 0 0 2 2
TOTAL* 22 4 4 0 2 32
*Total number of patients with corresponding HB scale in the column pre-SRS
** Total number of patients with corresponding HB scale in the row post-SRS
House Brackman Grading: Facial Nr Function
Pre & post-SRS (6 month) evaluation
(n=32)

24. Dosimetric comparison between BrainLAB & CyberKnife
Unilateral AN pt
Serviceable hearing function
Age <25 years
Size <3 cm
Contouring done with CT scan & MRI
GTV = post-contrast enhancement
PTV margin = 2 mm
Dose= 13-15 Gy single fraction
OARs (Choclea, Brainstem, Mesial temporal lobe)
Planning & calculation was done with appropriate calculation algorithms.
Isodose plans & DVHs generated by the two systems were compared
Prescribed isodose in both the systems were considered adequate to cover at least 95% of PTV
Planning with BrainLAB system
Forward planning
Arc no: 5-9
Planning with CyberKnife system
Inverse planning
Beamlet no: 70-150
(n=7)

25. CK BrainLAB p-value*
Mean tumour Vol (cc) 1.2±0.9 1.3±1 0.917
Conformity Index (CI) 0.53±0.06 0.58±0.07 0.225
10Gy Vol (cc) 3.2±1.1 5.2±1.6 0.017
5Gy Vol (cc) 11.8±4.9 16.8±6.2 0.129
2.5Gy Vol (cc) 39.9±17.2 52.3±19.8 0.238
Max dose brainstem (Gy) 4.9±3.1 4.7±2.6 0.935
Mean cochlea dose (Gy) 5.4±0.6 6.9±0.7 0.001
Mean mesial temporal lobe dose (Gy) 1.7±0.9 2.6±0.9 0.07
Dutta et al, J Neurooncol 2012
Comparison
BrainLAB & CyberKnife plan
No difference in target coverage
High dose spillage significantly less with CK
Dose to critical structures (cochlea & temporal lobe) significantly less with CK
*Non parametric test

26. Pt survey: Sx vs SRS (n=1553)
Issues Surgery^ RS*
Mean tumour size 25 mm 22 mm
Offers positive
recommendation
74% 95%
No change in employment 68% 69%
New balance problem 78% 7%
New onset tinnitus 57% 3%
New facial Nr Dysfunction 63% 10%
^ Martin etal Skull Base Surg 1996
* Kondziolka et al J Neurosurg 2001
Patient acceptance & toxicity profile better with radiosurgery
(n=1553)
New symptoms
Hearing function preservation is possible with SRS

27. SRS for AN FU >5 yrs ; <10 yrs
Q. Radiosurgery met your expectation? YES 92%
Q. Was radiosurgery good treatment? YES 95%
Q. Will you recommend radiosurgery to any one? YES 95%
(n=115)
Patient satisfaction survey*
Kondziolka et al NEJM 1998

28. Conclusions
Koos I&II: (AN <2.5 cm)
Serviceable hearing function: SRS preferred
Non-serviceable hearing function: SRS or surgery
Koos III&IV: (Larger tumour/ brainstem compression)
Facial Nr preservation not possible: Surgery
Facial Nr Preservation possible: Surgery / Safe Surgery + SRS
Surgery not possible: FSRT

29. Practice survey: Neurosurgeons choice*
37 yr male, 2.5 cm AN Unilateral symptomatic, serviceable hearing function
*Congress of Neurological Surgeons July 2002
Neurosurgeon’s age
(n=663)