This document summarizes outcomes from 496 patients with vestibular schwannomas treated with fractionated stereotactic radiotherapy between 1995-2007. Treatment failed in 11 patients (3%) who required salvage surgery. Radiological progression was observed in 30% of patients, including 9% whose tumor volume more than doubled. Larger initial tumor volumes and higher radiation doses were associated with increased radiological progression. Neurological side effects included new facial weakness in 1.6%, trigeminal paresthesias in 2.8%, and hydrocephalus in 0.9% of patients. Long term follow up shows radiological progression occurs frequently after fractionated stereotactic radiotherapy for vestibular schwannomas, though the
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Acaustic schwannoma
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
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
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)
23.
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)