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Small AVMs need treatment with either surgery or radiosurgery Deep seated & eloquent area AVMs need radiosurgery treatment Radiosurgery is single fraction, usually dose more than 18 Gy to the nidus Obliteration rate (cure rate) is 70-80% at 2-year evaluation Gammaknife / Linac based systems: need invasive frame Cyberknife: No need for invasive frame Out-patient procedure, excellent compliance Obliteration rate is similar to frame based systems Arteriovenous malformation [email protected]

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Small AVMs need treatment with either surgery or radiosurgery

Deep seated & eloquent area AVMs need radiosurgery treatment

Radiosurgery is single fraction, usually dose more than 18 Gy to the nidus

Obliteration rate (cure rate) is 70-80% at 2-year evaluation

Gammaknife / Linac based systems: need invasive frame

Cyberknife: No need for invasive frame

Out-patient procedure, excellent compliance

Obliteration rate is similar to frame based systems

Arteriovenous malformation

[email protected]

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Radiosurgery experience in AVMsAuthor (yr) Pt No FU (yr) Ave Dose

(Gy)Obiteration rate (%)

Complications

Flickinger et al 1987-1997

351 4.2 20 75 Necrosis, neurological deficits

French Dose Response study

100 5 20 708 pts had delayed complications

Pollock et al 144 2 20 73 20 pts had neurological deficit

AVM<3 cm; SM Gr I-IIIAt 2 yr FU with DSA: Obliteration rate is 70-80%Persistent Neurological deficit: <9%

[email protected]

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Author (yr) Pt No

FU (yr)

Vol Ave Dose (Gy)

Obiteration rate (%)

Complications

Jalali et al TMH

87 2 3.65 20 92 1pt had temporary neurological deficit

Kiran et alAIIMS

308 2 4.3 20 74 8 pts developed radiation edema 

Patel GCRI 2008

16 2 - 16 75 1 pt hd hemorrhage, 1 pt hd necrosis

Radiosurgery experience in AVMs from India

Only few prospective studies from India on AVM with SRS

Three studies showing at per obliteration rate & toxicity as western literature

SRS is feasible in our set [email protected]

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Rigid frame based SRS: Work Flow

Fixation of frame

DSA

CT Scan

Image fusion

Planning

QA (LUTZ test)

Treatment

One day procedureNeed admission of patientFrame fixed >6-8 hours

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Jalali, Dutta et al. J Cancer Res Ther, 2009

Min Max Mean SD

Nidus Volume (cc) 1.1 5.6 3.6 1.6

Marginal dose (Gy) 14.4 25 19.2 3.2

12 Gy normal brain vol (cc) 3.3 15.3 8.3 4.2

Maximum dose (Gy) 16 27.5 22 3.7

12 Gy marginal volume (cc) 0.3 9.6 5 4.4

Isodose Coverage (%) 80 91 87.5 3.3

Optic Chiasm dose (Gy) 0.5 0.5 0.4 0.01

Brainstem dose (Gy) 0.5 6 2.5 2.5

(n=23)

Nidus Vol: 3.6 ccMean marginal dose: 19.2 (14.4-25 Gy)

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Follow up (mo)  Mean

24.3 (1.57 to 71.2)

Median 22 Number of patient referred for SRS 87Number of patients planned for SRS 23 Number of patients treated with SRS 21

LFU status clinical examination No deficits 22 Neurological deficit persists after 2 yr FU 01Type of Imaging done for Assessment

MRI and MRA done at 2 yrs FU 15DSA 12

Imaging awaited on follow up 06Last Follow up status on Imaging

MRA proven obliteration 15 Obliteration confirmed on DSA 11

No Obliteration on DSA 01Complication after SRS

No complication 18Temporary worsening 02

Persistent neurological deficit 01

Follow up & obliteration rate

Obliteration rate at 2 yr follow up DSA: 92%

Median FU: 22 moObliteration rate: 92%Persistent Deficit: 1 pt

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Rigid frame (screw) based radiosurgery

Issues with frame fixationPain & hematomaFixed frame: 6-8 hoursOne day procedure

[email protected]

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Primary aim of the study:Evaluation of obliteration rate at 1 yearSecondary aim:Complication rateEvaluation of dose distribution parameters Evaluation of factors influencing obliteration rate

Title: Robotic -based stereotactic radiosurgery for selected AVMs: preliminary experience from Apollo Hospital, Chennai

Study type: Prospective observational study (DNB dissertation)

Study duration: 3 years (Initial data presented here)

Pt number: 30 (Accrued till date)Institute: Apollo Speciality Hospital, Chennai

Study design: Frameless Robotic SRS in AVM

[email protected]

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Eligibility Criteria Radiologically confirmed AVMs in brain.Spetzler Martin grade I-IIINidus size <4 cmHistory of prior hemorrhage, headache, tinnitus or convulsion.Willing for robotic radiosurgery treatment

Ineligibility criteriaActive haemorhageLarge AVMs (>5 cm nidus)Presence of aneurysm or AV shuntingPresence of calcification and intranidal fistulaPrevious radiation (n=30)

Study design: Frameless Robotic SRS in AVMTitle: Robotic -based stereotactic radiosurgery for selected AVMs: preliminary experience from Apollo Hospital, Chennai

[email protected]

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30 pts willing for Robotic SRS fulfilling the criteria accrued from Oct 2011 & have

more than 6 month FU were accrued for analysis

Site distribution: 14 in temporo-parietal region, 10 in frontal, 4 had intraventricular ,

1 in thalamic and 1 in cerebellar region .

Planning CT, CT angiogram, MRI, MR angiogram with 1 mm slice thickness.

Fusion and planning with Multiplan, Accuray system

Dose prescription was considered according to the flickenger’s model keeping

obliteration rate >80% & severe neurological toxicity <2%

6Dskull tracking .

Study design: Frameless Robotic SRS in AVM

(n=30)[email protected]

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Frameless SRS: Work Flow

Thermoplastic mask

CT AngioMR AngioCT Scan

Image fusionPlanning

QA

2 days procedureOUT PATIENTNo admission of patientTreatment with mask

Next day:

Day 1:

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Planning: Frameless Robotic SRS in AVM

(n=30)

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Treatment delivery: Frameless Robotic SRS in AVM

Treatment time: 20-45 minThermoplast based SRSPts received Dexa/ PPINo acute toxicity for majority of patients (one pt had brain oedema requiring MDT)

[email protected]

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Age (yr) mean (SD) 31.13 YRS

Range 6- 60 YRSGender male 17

Female 13

Duration of symptoms (mo) Mean5.8

Range1-60

Primary presenting symptoms

Headache alone 12 (40%)

Convulsions alone6(20%)

Neurological deficit alone3(10%)

Headache and neurodeficit1(3%)

Headache and convulsion8(27%)

Location TP region 14

Frontal10

Intraventricular region4

Thalamic1

Cerebellar 1

Demographic profiles: Frameless Robotic SRS in AVM

AVM size <1cm 0

1-2 cm 22- 3 cm 183 - 4 cm 10

SM grade

I-II18

III 12

Previous H’hge 12

Previous neurodeficit3

(n=30)

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Nidus Vol: 2.97 cc

Marginal dose:17.5 Gy (15-22 Gy)

Isodose prescription: 85%(80-90%)

Treatment time: 35 min (23-70 min

Dosimetric profile Min Max Mean

Nidus volume (cc) 0.46 7.7 2.97

Max dose (Gy) 15 22 17.5

Isodose coverage (% ) 80 90 85

Optic chiasm dose (cGy) 4 760 280

Rt eye dose (cGy) 3 448 146

Lt eye dose (cGy) 4 719 108

Beam lets 56 165 107

Treatment time (min) 23 70 35

HI 1.09 1.25 1.17

(n=30)

Dosimetric parameters: Frameless Robotic SRS in AVM

[email protected]

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Follow up duration(in months)

Mean* 14

Median 6-30

Pt condition on last followup

Normal* 18

Deficits

Nil

Type of imaging

MR angio at 6 months 30

MR angio at 12 months 16

MR Angio obliteration more than 1 yr follow up

Complete obliteration 13

Reduction in nidus volume 3

OUTCOMEMR ANGIO >1 YR - 16 ptCOMPLETE OBLITERATION - 13 pt (81%)

(n=30)

Results: Frameless Robotic SRS in AVM

Follow up: 14 monthsMedian Dose: 18 GyObliteration rate: 81%No Persistent Neurological deficit

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Framebased versus Frameless SRS in AVM

Frame based

Frameless

Rigid FrameFrame Fixed: 4-8 hrsPain/ HematomaAdmission

Thermoplastic maskMask with pt: <30 minNo Pain/ HematomaOut-patient

[email protected]

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Framebased versus Frameless SRS in AVMProblems with Screws

Pain / HematomaCompliance issueLong duration fixed frame (4-8 hrs)

‘Quality of life’ issue

Subdural hematoma 10%

[email protected]

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Framebased versus Frameless SRS in AVM

Frame based

Frameless

Dosimetry & treatment parameters

Nidus Vol: 3.6 ccMean marginal dose: 19.2 (14.4-25 Gy)Frame fixed 4-8 hrs

Nidus Vol: 2.97 cc

Marginal dose:17.5 Gy (15-22 Gy)

Isodose prescription: 85%(80-90%)

Treatment time: 35 min (23-70 [email protected]

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Framebased versus Frameless SRS in AVM

Frame based

Frameless

N=23Median FU: 22 moMedian does: 19.2 GyObliteration rate: 92%Persistent Deficit: 1 pt

N=16Median FU: 14 monthsMedian Dose: 18 GyObliteration rate: 81%No Persistent Neurological deficit

Obliteration rate & Toxicity

[email protected]

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Frame based versus Frameless SRS in AVM

- It seems, Obliteration rate in both frame based & frameless almost similar

- In frame based system, frame usually used for 4-8 hrs & frameless system only 30-45 min

- Compliance higher with frameless, out-patient treatment

- ‘Early quality of life’ better with frameless

- In Multiplan planning system dosimetric parameters exciting [email protected]

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Flickinger et al.. Rad Onc 2002; 63:347-354.

Flickinger model

Dose prescription (Isocentre)

Marginal dose ( Gy)

12 Gy normal brain vol (cc)

Obliteration:Depends upon marginal dose

Complication:Depends upon 12 Gy normal brain vol

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Beam reduction effect on 12 Gy Normal brain Vol

Optimum plan after approval taken for study

Marginal dose: 22 Gy; Pres Isodose: 85%Coverage: 99.5%Nidus size: 2.5 cmNidus Vol: 5.2 cc12 Gy Normal Brain Vol: 22.5 cc

Beams: 85Total MU:14414Min MU: 15 Max MU: 622

Beam reduction done by reducing beams with minimum MU in steps of 50, 100, 150, 200, 250 MU Collimator size kept same

Prescription Isodose changes to keep Nidus coverage >99%[email protected]

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0 50 100 150 200 250

8579

59

51

3326

Beam reduction effect on 12 Gy Normal brain Vol

No of Beams

Beam reduction in steps of 50 MU

Increasing the beamlets MU cutoff limit reduce low MU beams [email protected]

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85 79 59 51 33 26 23 22 21 20

CI 1.67 1.67 1.85 1.78 3.12 3.54 3.75 3.96 3.83 3.7

nCI 1.69 1.69 1.86 1.79 3.14 3.57 3.77 3.99 3.87 3.73

HI 1.18 1.18 1.2 1.2 1.72 1.85 1.92 2 2 2

0.25

0.75

1.25

1.75

2.25

2.75

3.25

3.75

4.25C

I /

nC

I /

HI

MU 14106 14190 14512 14189 16500 17523 17171 18558 17621 17299

Coverage (%) 99 99.1 99.3 99.1 99.2 99.2 99.3 99.2 99.2 99.1Pres Isodose 85 85 83 83 58 54 52 50 50 5012Gy Vol 23.5 26.4 27.5 25.8 36.6 39.9 44.6 45 45.4 46.8

Beam reduction effect on 12 Gy Normal brain Vol

[email protected]

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85 79 59 51 33 26 23 22 21 20

23.526.4 27.5

25.8

36.6

39.9

44.6 45 45.4 46.8

12Gy Normal brain Vol (cc)

0 50 100 150 200 250

85

79

59

51

33

26

No of Beams

85 79 59 51 33 26

Beam reduction effect

Beam reduction effect on 12 Gy Normal brain Vol

Beams

Correlation Coefficient: 95.6% p-value: 0.003

Pearson correlation [email protected]

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Beam reduction effect: Neurodeficit probability

85 79 59 51 45 33 26 22 210

5

10

15

20

25

30

35

40Occip-italFrontalParital

Pers

isten

t Neu

rolo

gica

l def

icit p

roba

bility

(%)

Beam numbers

20-50% increase in PND with beam reduction

According to Flickinger et al.. Rad Onc 2002; 63:347-354.

[email protected]

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Nidus Diameter

Coverage (%)

Pres Isodose CI

2.5 cm 99 85 1.673.5 cm 99.4 77 1.354.5 cm 99.9 73 1.3

Effect of increased nidus vol on 12Gy Normal brain Vol

Nidus size: 2.5 cmNidus Vol: 5.2 ccMarginal dose: 22 GyCoverage: 99.5%Presription Isodose: 85%

0.5 cm margin to NidusNidus diameter: 3.5 cm

1 cm margin to NidusNidus diameter: 4.5 cm

Marginal dose: 22 GyCoverage >99%

Change CollimeterChange prescription Isodose

Evaluate 12Gy Normal brain Vol

PTV2.5

PTV3.5

PTV4.5

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Nidus Diameter Beams

Correlation Coeff p-value

12Gy Vol (cc)

Correlation Coeff p-value

2.5 cm 8599.6 0.003

23.593.4 0.0523.5 cm 167 63.6

4.5 cm 227 247

Series1

85

167

227

2.5 cm Nidus

3.5 cmNidus

4.5 cm Nidus

p-value: 0.003

Series1

23.5

63.6

247

2.5 cm Nidus

4.5 cm Nidus

p-value: 0.052

3.5 cmNidus

No of Beams 12Gy Normal Brain Vol (cc)

Impact of larger nidus

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Obliteration rate: It seems, Frameless SRS system is similar to frame based

systems

Frameless system: Compliance is excellent, out-patient procedure

Multiple beamlets may have dosimetric advantages with lesser 12 Gy normal

brain volume and acceptable marginal dose

‘Quality of life’ and acceptance by patient is excellent with frameless system

AVM- Conclusions

[email protected]