This document discusses the use of radiosurgery techniques like Gamma Knife and CyberKnife for treating various brain tumors and vascular malformations. It provides details on the indications, dosimetry, and outcomes of these techniques for conditions like meningiomas, acoustic schwannomas, brain metastases, arteriovenous malformations (AVMs), and craniopharyngiomas. CyberKnife is described as having sub-millimeter accuracy similar to Gamma Knife but with more conformal dose distributions and the ability to treat larger or multiple lesions in a fractionated schedule. Indian studies show high rates of tumor control and low complication rates following radiosurgery for conditions like AVMs.

1. Radiosurgery in brain tumours
Dr Debnarayan Dutta, MD
Consultant Radiation Oncologist
Apollo Speciality Hospital, Chennai
duttadeb07@gmail.com

2. CNS Tumours
Total number of tumours 132
Total number of malignant glial tumour ~ 20
WHO Classification. Louis D ; Acta Neuropathol 2007

3. Radiation therapy
Conventional RT:
1.8-2 Gy/#
Majority of the tumours are treated with Conv RT
Hypofractionated RT:
>2 Gy/#
Mainly for palliative treatment
Radiosurgery:
Single fraction high dose treatment
Usually curative intent
Fractionated Radiosurgery:
Short course high dose treatment
Usually curative

4. Radiosurgery: tools
Gamma-Knife
LA based SRS Systems
BrainLAB
Novalis
Trilogy
Tomotherapy
CyberKnife

5. Gamma knife
• Gamma-knife: 201 Cobalt source
• Only for intracranial lesions
• Rigid/ fixed frame required
• Single fraction treatment

6. Gamma-knife
Indications
- Small Meningiomas (<3 cm)
- Small acuastic schwannoma (<3 cm)
- Solitary / oligo brain metastasis with controlled primary (RPA Class I)
- Small residual LGG
- AVMs (<3 cm)
- Trigeminal neuralgia (Functional disorder)
More than 40 years experience / results with Gamma-Knife

7. CyberKnife: Unique properties
Highly precise treatment delivery
Motion management method
Tumour tracking
‘Dose painting’
Excellent dose distribution
Fractionation schedule
No rigid fixation

8. ‘CyberKnife is an extension of Gamma-Knife’
CK & GK: Similarity
- Principles of ‘field arrangement’
- Dose distribution pattern
- Multiple isocentre
-Treatment principles
- Treatment delivery accuracy similar
- Delivered dose in single fractions
- Intra-cranial indications
Hence, all the indications of GK are indications of CK also

9. Cyberknife
Indications for single fraction treatment as Gamma-Knife
- Small Meningiomas (<3 cm)
- Small acuastic schwannoma (<3 cm)
- Solitary / oligo brain metastasis with controlled primary
- Small residual LGG
- AVMs (<3 cm)
- Trigeminal neuralgia
- Rec High grade glioma
- Craniopharyngioma
- Pituitary tumour
More than 40 years experience / results with Gamma-Knife

10. Cyberknife Vs Gamma-Knife: Dissimilarity
GK CK Comments
Immobilization device Rigid frame Orfit CK has favorable orfit
RT source Co60 6MV LA GK need to replace sources every
5/6 yrs
Planning No complex planning Inverse planning Favorable dosimetry in CK
Planning method Simple Complex Even neurosurgeons can plan in
GK
Isodose prescription Usually 50% Usually 80-95% GK: more dose heterogeniety
Fractions Single May treat multiple fraction Radiobiology favorable in CK
Tumour size Only smaller lesions can
be treated
Larger lesions also can be
treated in fractionated
schedule
Increased indications with CK
Energy source Radiation Electricity GK can work with less electricity
Verification Not possible Possible Even Intra-fraction movement can
be corrected
Indications Only brain lesions Both extra & intra cranial CK more economical

11. Cyberknife Vs Gamma-Knife: Dissimilarity
Advantage of Inverse planning
GK planning
CK planning
Dose to mesial temporal lobe & Choclea is higher with GK
Mean dose to mesial temporal lobe >6 Gy with SRS: IQ decline
Romanalli, Lancet 2009

12. % of patient with >10% drop in IQ
Left temporal lobe DVH
p=0.39
p=0.06
p=0.03
p=0.06
Volume (cc)
Jalali , Dutta et al IJROBP 2009

13. PTV margin in brain tumour
CTV-PTV Margin
Systemic
Error ()
Random
Error ()
ICRU 62 Strooms Van Herk’s
NR only Group:
Ant-Posterior 0.1 1.36 1.05 mm 1.15 mm 1.20 mm
Med-lateral 0.28 1.04 1.01 mm 1.29 mm 1.43 mm
Sup-Inferior 0.52 1.37 1.48 mm 2.0 mm 2.26 mm
NRF Group:
Ant-Posterior 2.24 1.28 3.14 mm 5.38 mm 6.50 mm
Med-lateral 0.78 1.41 1.77 mm 2.55 mm 2.94 mm
Sup-Inferior 0.94 1.39 1.91 mm 2.85 mm 3.32 mm
PTV margin: 3 mm.
Budrukkar , Dutta et al, JCRT 2008
Prospective study
Two different head rest (NR & NRF)
220images (NR 100, NRF 120)
Error estimation with 2D EPID

14. Cyberknife Vs Gamma-Knife Vs X-Knife:
CK: Accuracy similar with Gamma-Knife
Treatment delivery accuracy:
GK: ~1 mm
CK : ~1 mm
LA based SRS: 1-2 mm (iso-centric inacurracy; LUTZ test)
PTV margin:
CK: <1 mm
GK: <1 mm
LA based SRS: 1-2 mm
GK/CK LA based SRS
CK has the accuracy of GK and flexibility of LA based SRS

15. fSRS
Extended Indications for multiple fraction treatment
- Larger meningiomas (>3 cm)
- Larger acuastic schwannoma (>3 cm)
- Large solitary / oligo brain metastasis with controlled primary
- Larger residual LGG
- AVMs (>3 cm)
- Chordomas
- Rec HCC
- Craniopharyngioma
- Pituitary tumour
Short term data with robotic radiosurgery

16. New experiences with fSRS
Pre-Treatment Post-Treatment
- More necrosis with CK than SRT (25Gy/5# Vs 54Gy/30#)
- Difficult to have radiological interpretation
- Require longer duration of steroid
- Associated with more oedema

17. Outcome measures in benign/ low grade tumours
Radiological response may not be appreciable
Lack of progression is ‘control’ in low
grade/benign tumours
Hence, function preservation is the mainstay of
assessment of Rx outcome
Function assessment:
Neuro-psychological assessment: IQ assessment
Neuro-cognitive assessment: LOTCA
Activities of daily living: Barthel’s , FIM FAM
Quality of life

18. ADL in evaluation of efficacy in benign/low grade tumour
(n=38) Dutta, Jalali JNO 2008

19. Response with fSRS in benign tumour
Conventional RT ‘lack of progression’ is usual.
In a few patients we have observed regression or
complete response

20. New experiences with fSRS
Radiobiology & dose equivalent may be unpredictable with high dose/Fr
Conventional BED calculation may not be appropriate
Need to use different methodology for calculation of ‘dose equivalence’
60Gy @ 2Gy/Fr equivalence dose

21. New experiences with fSRS
Low dose region is less with CK compared with LA based SRS
Balaji, Dutta, Mahadev, AROI 2010 (Abstr)

22. Secondary malignancies: Impact of low dose region
Low dose region is less with CK compared with LA based SRS
Dose factors & sec malignancies
Sec malignancies high with higher 1-10 Gy volume Coudi 2010

23. Experiences with SRS/ fSRS
Brain metastasis
Acaustic schwannoma
AVMs
Meningiomas
Pituitary tumour
Craniopharyngioma
Rec HGG
New indications

24. Demography data: Brain tumours
Incidence*
CBTRUS SEER
All cases 14.8 6.4
Benign 7.4
SEX-Male 14.5 7.6
Female 15.1 5.3
Estimated new cases 43,800 18,500
Paediatric
All 4.3
Male 4.5
Female 4.0
Lifetime Risk
Male 0.65%
Female 0.50%
Prevalence#
CBTRUS
All cases 130.8
Benign 97.5
Malignant 29.5
Uncertain behaviour 3.8
*(per 1,00,000 person-years)
# (per 1,00,000 population)
Brain metastasis
7-10 times of primary tumour

25. Brain metastasis: SRS
Problem with Indian Subcontinent
Median age of presentation
Developed Countries* Tata Hospital data**
Metastatic brain Tumour 61 yrs 49.4 yrs
Anaplastic astrocytoma 49 yrs 36 yrs
Glioblastoma 62 yrs 50 yrs
Oligodendroglioma 41 yrs 37 yrs
Pituitary adenoma 39 yrs 41 yrs
Meningioma 55 yrs 46.5 yrs
Malignant Tumours: presentation one decade earlier in our data
* SEER and CBTRUS.
**Tata Memorial Hospital NeuroOncology registry 2006
Jalali & Datta J Neurooncol (2008) 87:111–114

26. Brain metastasis: WBRT alone
RPA class Features MS (mo)
1 KPS>70; Age<65; controlled primary;
no extracranial disease
7.1
2 KPS>70; Age>65; Uncontrolled primary;
extracranial metastasis
4.2
3 KPS<70 2.3
Gasper et al; 1999

27. Brain metastasis: SRS/Sx
Prospective studies
MS (mo) p-value
Patchel WBRT+ Sx 9.2 0.01
WBRT only 3.4
Vecht WBRT+ Sx 10 0.04
WBRT only 6
Mintz WBRT+ Sx 5.6 0.24
WBRT only 6.3
Andrews WBRT+ Sx 6.5 0.13
WBRT only 5.7
Kondriolka WBRT+ Sx 11 0.22
WBRT only 7.5

28. SRS: Brain metastasis
Advantages
Surgery Radiosurgery
Lesion Larger (>4 cm), Non-eloquent
area
Small, deep lesions,
eloquent area
Effect Rapid resolution of mass effect Minimally invasive
Tumour removed Sterilized
Histopathology Confirmed Not
Anesthesia Required No
Steroid Tapped faster longer
Follow up Less intensive More
Suh J et al; NEJM 2010

29. SRS: Brain metastasis
Well defined on imaging (MRI & CT)
Spherical or pseudospherical shape
Most <4 cm in Max diameter
Generally noninfiltrative
Located in grey-white junction
Suh J et al; NEJM 2010
Ideal lesions for SRS

30. Brain metastasis: fSRS
Prospective studies: Larger tumours
Study Median Vol (cm3) KPS Multiple
lesions
MS (Mo)
Alexender (1995) 3 80 31% 9.4
Aucher (1996) - - 0% 13
Breneman (1997) <4 cm 90 57% 10
Shiou (1997) 1.3 90 46% 11
Shirato (1997) >2 cm:36% 60 0% 9
Pirzhall (1998) - 80 26% 5.5
Kim (2000) 2.1 90 15% 11
Nishizaki (2006) 7.2 80 45% 13
Nishizaki; Minim Invas Neurosurg 2006

31. Epidemiology
- Account for 10% SAH and 1% of strokes
- Autopsy studies show 4-5% incidence in general population
- Males: Female 2:1
Presentation
- Hemorrhage (50%) usually during 2nd-4th decades
- 10-20% risk of death if bleeds
- 10-20% risk of long-term disability
- Increased risk of re-bleed of 6% during first year after initial bleed
- Seizures (25%)
- HA (15%) migraine-type
- Pulsatile tinnitus
AVMs

32. Dose response curve: obliteration rate
3Yr
obliteration
5 year
15-20 45% 85%
20-25 55% 90%
25-30 75% 75%
Obliteration after SRS depends upon marginal dose
Flickinger et al.. Rad Onc 2002; 63:347-354.

33. Complications : AVM Radiosurgery
Persistent neurological toxicity depends upon 12 Gy normal brain volume & location
Flickenger et al. IJROBP, 38(3):485-490,1997.

34. AVMs: SRS dosimetry
Dose prescription (Isocentre)
Marginal dose ( Gy)
12 Gy normal brain volume (cc)
Obliteration depends upon: marginal dose
Complication depends upon: 12 Gy normal brain volume

35. Radiosurgery in AVMs
Gamma Knife LA based SRS Cyberknife
Accuracy Sub-millimeter
accuracy
not Sub-millimeter
accuracy
PTV margin ~0-1 mm 1-2 mm ~0-1 mm
Isodose coverage 50% 80-90% 80-90%
Dose inhomgeniety high less less
Normal brain dose high less least
Complication probability high high Expected to be
lower
Obliteration probability same same same
Cyberknife: sub-millimeter accuracy of gamma knife & higher dose homogeniety of LA based SRS

36. SRS in AVMs: Indian data (n=23)
Number of patient referred for SRS 87
Number of patients planned for SRS 23
Number of patients treated with SRS 21
LFU status No deficits 22
Neurological deficit persist 01
Type of Imaging done for Assessment
MRI and MRA done at 2 yrs FU 15
DSA 12
Imaging awaited on follow up 06
Last Follow up status on Imaging
MRA proven obliteration 15
Obliteration confirmed on DSA 11
No Obliteration on DSA 01
Pre-SRS
Post-SRS 2 yr FU
Complete obliteration rate at 2 yrs DSA evaluation 92%
Complication after SRS
No complication 18
Temporary worsening 02
Persistent neurological deficit 01
Jalali, Dutta et al. J Cancer Res Ther, 2009

37. Large AVMs
n Median
FU (mo)
Results LTNS
Chang (2008) 55 36 mo OR- 36% 15%
Pollock (2000) 10 (23) 12 mo 12 Gy Vol dose
acceptable
-
Larger AVMs are treatable without increasing lat e neurological toxicity
Pollock IJROBP 2010

38. Meningiomas: SRS
- SRS is an option for small meningiomas (Incidental findings or symptomatic )
- Dose: 10-15 Gy; single Fr
- Local control rate: 80-90% at 10 yrs
- However, now emerging data, larger lesions (para-sagital) / Recurrent meningiomas may
be treated with fractionated approach
CK Society website 2010

39. Atypical/ anaplastic meningiomas: SRS

40. Craniopharyngioma
• Epithelial tumou rising from rathkes pouch remnants
• 2-5% of all primary intracranial tumours
• Common age of presentation <20 yrs
• 5-15% of primary tumour in children
Two histopathological types:
1) Aadamantinomatous type-mainly
occurs in children
2) papillary type- occurs exclusively in adults.
• Increasingly treated with conservative surgery + RT
• Good results with RT; 70-85% long term control
• Relatively high risk of treatment related effects
Age & Sex distribution Review of 144 published data; Adamson & Yasargil 2008

41. Recurrence rate after only partial excision
Author yr n Recurrence FU (yrs)
Carbezudo 1981 14 12 5-30
Carmel 1982 14 10 6.1
Djordjevic 1879 15 8 -
Hoff 1972 18 16 10
Hoffman 1977 15 8 2-16
Lichter 1977 9 7 1-20
McMurrary 1977 9 7 1-14
Shapiro 1979 9 7 7.8
Stahnke 1984 12 6 6.9
Sweet 1976 5 4 1-21
Thomsett 1980 11 10 8.2
131 93 (71%)
Recurrence rate 71% after only partial excision

42. Surgery alone vs Sur+ RT
Subtotal resection + RT: higher PFS
Stripp et al IJROBP 2004
(n=76)

43. SRS/fSRS: Craniopharyngioma
Veeravagu et al, Neurosurg Focus 2010

44. Craniopharyngioma: SCRT- IQ assessment (n=18)
VQ: Verbal Quotient
PQ: Performance Quotient
MQ: Memory Quotient
FSIQ: Full Scale IQ
120
110
100
90
80
70
60
50
40
30
20
10
0
Pre-RT 6 month 24 month 36 month
Mean IQ scores
Mean IQ Scores
VQ
PQ
FSIQ
MQ
35
30
25
20
15
10
5
0
Pre-RT 6 month 24 month 36 month
Mean Score
Mean Anxiety Score
Anxiety Trait (C1)
Anxiety State (C2)
• Mean IQ Scores are maintained at post-RT follow up.
• State anxiety had reduced after RT.
Dutta, Jalali et al WFNO 2009

45. Pituitary tumour: SRS
Problems with SRS:
Pituitary tumour close to Optic pathway/ chiasm.
Tumor close to chiasm may not be treated with surgery
Also not possible to treat with single fraction SRS
Constraint to chiasm: 10 Gy
SRS dose required: 12 Gy
fSRS is possible
Higher dose can be delivered without increasing chiasm injury
SRS/ fSRS increases early hormonal control without increasing toxicity (12 vs 40 mo)
Plowman Clinical Endocrinology 1999

46. Recurrent HGG: SRS studies
Romanelli, Neurosurg focus 2009

47. Recurrent GBM: SRS
Conti 2010
SRS/fSRS SRS+TMZ
MS (mo) 6.5 12
6-mo PFS (%) 20 60
Radionecrosis - 10%
Corticosteroid 60% 80%

48. Conti 2010
Recurrent GBM: Survival function

49. HGG: IMRT + CK boost Protocol
Eligibility Criteria:
Histopathologically confirmed high grade gliomas (AA / GBM).
Karnosky performance status >70.
Willing for IMRT and Cyberknife treatment.
(ethical committee approved)
Methodology:
Conformal RT (50 Gy/25#/5 wks) CK 20Gy/5#
│││││││││││││││││││││││││││││││││││ │││││
Conc TMZ (75mg/m2) x 6 wks Adj TMZ (200 mg/m2) x 6 cy
End point:
• Survival function,
• Activities of daily livings
• QOL

50. New Indications: SRS
-Temporal lobe epilepsy
- Resistant seizure disorder
- Behavioral disorders
- Mood disorder
- Obesity
- Child hood attention deficit disorder / absence seizure
- Skull base tumour

51. Quality of life is paramount important
EORTC QLQ C30 & BN20 Score in HGG (n=255)
TMH data¶ Taphoorn et al*
EORTC QLQ-C- 30*
Global score 51.7 62.8
Emotional 61.4 69.3
Cognitive 67.6 -
Social Function 69.2 67.5
Fatigue 44.4 35.3
Pain 39.4
BN-20**
Future uncertainty 23.1 40.1
Communication deficit 34.9 18.6
Seizures 38.2 NA
Drowsiness 18.5 26.4
Future uncertainty & communication deficits are different in our data & western data
Jalali, Buddrukar, Dutta JNO 2009

52. SRS in brain tumours
Conclusions
- SRS is one of the standard of care is many small & benign brain tumours.
- It seems, clinical outcome of robotic radiosurgery is similar to GK in these subset of pts
- fSRS is an attractive option in larger benign/low grade and malignant tumours