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Radiosurgery Beyond the Brain:Advances in the Treatment of Extracranial Radiosurgery

Haidy Lee MD

May 12, 2009

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Background• Extracranial radiosurgery = Stereotactic Body

Radiotherapy (SBRT)• Very large doses of extremely precise ionizing

radiation• A highly specialized form of image-guided

radiotherapy (IGRT)• Given in 1-5 fractions

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SBRT is biologically more potent

⎟⎟⎠

⎞⎜⎜⎝

⎛+=

βαdndBED 1

n = number of fractions

d = dose per fraction

α/β = tissue characteristic

Beware: Linear-quadratic model may not be accurate with these fraction sizes!

Fowler, et al. In Stereotactic Body Radiation Therapy, Lippincott Williams & Wilkins, 2005.

Slide courtesy of Brian Kavanagh, U. Colorado

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Intracranial Stereotactic Radiosurgery versusSBRT

Slide courtesy of Brian Kavanagh, U. Colorado

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Patient Immobilization

BodyFix dual vacuum system with abdominal compression

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Patient Immobilization

Aquaplast mask

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Intracranial Stereotactic Radiosurgery versusSBRT

Slide courtesy of Brian Kavanagh, U. Colorado

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Repositioning

• Accuracy between treatment planning and treatment

• Multiple treatments• Patient comfort

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Intracranial Stereotactic Radiosurgery versusSBRT

Slide courtesy of Brian Kavanagh, U. Colorado

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Imaging

• CT scan or x-rays on treatment couch• Registration of anatomy• Fiducial references

Image showing both kVCT (grey) and MVCT (green)

Before Registration After Registration

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Intracranial Stereotactic Radiosurgery versusSBRT

Slide courtesy of Brian Kavanagh, U. Colorado

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Respiratory Control

• Abdominal compression• Respiratory gating• Tumor tracking

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Abdominal Compression

• Paddle used to induce shallow breathing

Elekta Stereotactic Body Frame

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Beam ON Beam ONBeam OFF

tumortumor

tumor

Respiratory Gating

Slide courtesy of P. Keall, VCU

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Tumor Tracking

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Treatment Delivery

• Ablative doses• Conformal delivery• Rapid dose fall off

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Treatment Delivery

ManufacturerSBRT

Radiation Unit

Image Guidance

RespiratoryManagement

FieldCollimation

Unit restrictedto SRS

Accuray CyberKnifeDual Fixed X-ray;

Simultaneous Imaging

Frameless real time fiducial based tracking Circular cones only Yes

BrainLab NovalisDual Fixed X-ray;

Sequential Imaging

Respiratory gating with IR markers

Micro-MLC with minimum of 3 mm

at isocenter or circular cone attachments

No: Field size limited to 10x10 cm at

isocenter

Elekta Synergy S

Rotating kV x-ray for fixed planar

views and kVCBCT

Active breathing control (ABC): Breath hold technique and frame/abdominal

compression

Micro-MLC with minimum of 4 mm

at isocenter or circular cone attachments

No, Field size limit

16 x 21 cm atisocenter

Siemens Primatom

In-room CT scanner with

couch coupled to linac

Frame/ abdominal compression

MLC with 1 cm leaf or circular cone

attachmentsNo

Tomotherapy HiArtTomotherapy Fan beam MVCT Frame/ abdominal

compression

Minimum MLC leaf configuration of 6 mm and 6 mm jaw

width

No

Varian Trilogy

Rotating kV x-ray for fixed planar

views and kVCBCT

Respiratory gating with IR marker system

Micro-MLC with minimum of 5 mm

at isocenter or circular cone attachments

No

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Treatment Delivery

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Indications• Organs

– Parallel vs Serial Organs• Definitive treatment

– Early stage NSCLC– Hepatoma– Prostate– Pancreas

• Palliative treatment– Oligometastatic disease

• Lung, Liver, Spine– Recurrence

• Prior radiation therapy

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Indications• Organs

– Parallel vs Serial Organs• Definitive treatment

– Early stage NSCLC– Hepatoma– Prostate– Pancreas

• Palliative treatment– Oligometastatic disease

• Lung, Liver, Spine– Recurrence

• Prior radiation therapy

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Indications• Parallel Organs• Serial Organs

Lung: Serial organ structure proximally becominga parallel organ structure distally

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Tumors in serial organ structures are not always candidates for SBRT due to risk of downstream injury

Indications

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Early stage NSCLC

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Early stage NSCLC56 year old woman with a 1.2 cm biopsy proven right lung lesion as her only site of disease

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Early stage NSCLCIsodose distribution

37.5Gy in 3 fractions

Axial

Sagittal

c Coronal

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Early stage NSCLCThe planning scan is co-registered with the MVCT scan prior to

treatment to ensure accuracy of delivery

Planning CT in grey

MVCT in yellow

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Pretreatment scan 2 months post treatment

3 months post treatment 6 months post treatment

- early fibrosis

12 months after treatment

12 months post treatment

- fibrosis

Early stage NSCLC

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Metastatic sarcoma 20 Gy in one fraction

Pretreatment CT scan 2 months post treatment

Palliation Lung

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Prospective Liver Metastasis SBRT Clinical Trials

• Hoyer phase II colorectal metastases (n = 44); 45 Gy/ 3 fxs 2-year actuarial lesion control rate of 86%

• Kavanagh phase I/II trial (n = 36)36-60 Gy/ 3 fxs without reaching DLT (I); 93% local control at 18mo with no grade 4 toxicity (II)

Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 2006;45:823-830.Kavanagh BD, Schefter TE, et al. Interim analysis of a prospective phase I/II trial of SBRT for liver metastases. Acta Oncol 2006;45:848-855.

PalliationLiver

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Palliation Liver

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First Spinal RS• University of Arizona

– 45 Gy external radiation previous XRT

– 8-10 Gy for recurrent tumor in single fraction

• Setup aided by surgically implanted device that docked into external frame (FIGURE)

• 5 patients followed median 6 months– Good local control and palliation

described

Hamilton et al, Neurosurgery. 36(2):311-319, February 1995

Palliation Spine

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• Continuous 20-sec MRI during normal breathing • Spinal cord motion is generally small (< 0.5 mm)

Palliation Spine

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Study n Dose (Gy) Pain Improvement

Jin (2007) 196 10-18 85%

Gibbs (2007) 74 16-25 84%

Gerszten (2007) 500 12.5-25 84%

Gerszten (2005) 26 16-20 92%

Degen (2005) 51 10-37.5 97.3%

Gerszten (2004) 115 12-20 94%

DeSalles (2004) 14 8-21 50%

Benzil (2004) 31 0.5-50 94%

Ryu (2004) 49 10-16 85%

Sheehan 34 18-24 90%

Pain Relief

PalliationSpine

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Study n Control

Gerszten (2007) 500 90%

Gwak (2006) 3 33%

Ryu (2004) 49 95%

Sheehan 34 90%

Tumor Control

PalliationSpine

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Palliation Spine

Isodose Distribution24 Gy in 3 fractions

Axial Coronal Sagittal

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MSKCC Spinal SBRT Experience

• 93 patients, 103 lesions– No spinal cord compression

• Single fraction 18-24 Gy– CTV usually vertebral body– PTV = CTV +2mm– Spinal cord max 12-14 Gy

• Better control at higher dose (24 Gy) than lower (above)

Yamada et al, Int J Rad Oncol Biol Phys, 2008

Metastatic Colorectal CA

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Spinal Target volumes, from “Partial Volume Tolerance of the Spinal Cord and Complications of Single-Dose Radiosurgery”

Ryu et al, Cancer, 2007

• Cord drawn 6mm above and below target• Major constraint: no more than 10% of cord receives

dose above 10 Gy• Only 1 observed cord complication among 177 pts

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Note: Patient was heavily pre-and post-treated with chemotherapy.Symptoms included RLE weakness, resolved with steroids

Toxicity“Partial Volume Tolerance of the Spinal Cord and Complications of Single-Dose Radiosurgery” Ryu et al, Cancer, 2007

Pretreatment Isodose Plan

Post treatment

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Toxicity

Freedom from grade 3-5 toxicity

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Toxicity

• 40 patients treated at UVA

• T1-2 non-small cell lung cancer

• 45-60Gy in 3 fractions

Number (%) n=40

Chest Wall pain 9 (23%)

Rib Fracture 2 (5%)

Pneumonitis

Grade 1 5 (12%)

Grade 2 1 (2%)

Grade 3 1 (2%)

Median (range)

Onset of Pain (months) 7.1 (0.6 - 32.3)

Time to rib fracture (months) 20.6 (8.9 – 33.3)

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Future Directions

• Radiobiology• Interaction with chemotherapy,

targeted agents, radioprotectors• Improved Treatment Delivery• Long-term outcome data• Economics

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Disclosures

• None

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Credits

University of Virginia Department of Radiation Oncology– Paul Read MD, PhD– Stan Benedict PhD– Ke Sheng PhD– Jing Cai PhD– Neal Dunlap MD– Jason Sheehan MD (Dept of Neurosurgery)