Radio surgical treatment of cranial lesions; Refining the art

Mohamed Abdulla M.D.Prof. of Clinical Oncology

Kasr Al-Aini School of MedicineCairo University.

Current View in 2015:

• Basic Definition by Leksell:“The delivery of a single high dose of irradiation to a small and critically located intracranial volume through the intact skull”

• Improvements of Pre-requisites of Application: 1. Neuroimaging.2. Neuroanatomy.3. Reliable radiation therapy delivery system.

• Achievements:1. Better understanding of radiobiological considerations.2. Introduction of more reliable radiation therapy devices.3. Extension to fractionated treatment (Extra-cranial targets).4. Dose/Volume constraints for normal tissues (OAR).

New Insights of SRS Radiobiology:

IR DNA Double Strand Breaks Variable Cellular Abilities of Repair Radiosensitivity.5Rs of Radiobiology:1. Repair.2. Redistribution.3. Repopulation.4. Reoxygenation.5. Radiosensitivity

Withers HR. The four R’s of radiotherapy. In: Lett JT AH, editor. Advances in Radiation Biology, Vol 5. New York: Academic Press; 1975. p. 241-271. Steel GG, McMillan TJ, Peacock JH. The 5Rs of radiobiology. Int J Radiat Biol 1989;56:1045-1048.

New Insights of SRS Radiobiology:

Radiobiological Effect of Single Fraction (> 10 Gy):1. Endothelial cell Damage Cytotoxicity & Apoptosis.2. Vascular Damage at High Doses ++ 2nd Cell Killing.3. Enhanced Anti-Tumor Immunity after Tumor Irradiation.4. Tumor Hypoxia is of Less Importance.

Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005;8:89-91.Clement JJ, Tanaka N, Song CW. Tumor reoxygenation and post- irradiation vascular changes. Radiology 1978;127:799-803. Hiniker SM, Chen DS, Knox SJ. Abscopal effect in a patient with melanoma. N Engl J Med 2012;366:2035. author reply 2035-2036.

• Brain is a late responding tissue; @/β = 2.• Radiobiological Classification of Cranial Targets:

1. Late responding target embedded in late responding tissues: AVM.

2. Late Responding target surrounded by late responding tissues: AN.

3. Early responding target embedded in late responding tissue: Low Grade Glioma.

4. Early responding target surrounded by late responding tissue: GBM and High Grade Glioma.

New Insights of SRSRadiobiological Complexity of Cranial Targets:

International Journal of Radiation Oncology Biology Physics, vol. 25, no. 3, pp. 557–561, 1993.

New Insights of SRSRadiobiological Complexity of Cranial Targets:

Cancer Treatment Reviews 37 (2011) 567–578

Gamma-Knife

LA based SRS Systems

BrainLAB Novalis Trilogy Tomotherapy

CyberKnife

Radiosurgery Tools:

Gamma knife

• Gamma-knife: 201 Cobalt source

• Only for intracranial lesions

• Rigid/ fixed frame required

• Single fraction treatment

Gamma-knifeIndications

- 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

CyberKnife: Unique propertiesHighly precise treatment delivery

Motion management

method Tumour tracking

‘Dose painting’

Excellent dose distribution

Fractionation schedule

No rigid fixation

‘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

CyberknifeIndications 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

Cyberknife Vs Gamma-Knife: DissimilarityGK CK Comments

Immobilization device

RT source

Rigid frame

Co60

Orfit

6MV

LA

CK has favorable orfit

GK need to replace sources every 5/6 yrs

Favorable dosimetry in CK

Even neurosurgeons can plan in GK

GK: more dose heterogeniety

Radiobiology favorable in CK

Increased indications with CK

Plannin

g Planning

method

No complex

planning Simple

Inverse

planning

ComplexIsodose prescription

Fractions

Tumour size

Usually

50% Single

Only smaller lesions canbe treated

Usually 80-95%

May treat multiple fraction

Larger lesions also can be treated in fractionated schedule

Electricity

Possible

Energy source

Verificatio

n

Radiation

Not possible

GK can work with less electricity

Even Intra-fraction movement

canbe corrected

CK more economical

Indications Only brain lesions Both extra & intra cranial

Cyberknife Vs Gamma-Knife: DissimilarityAdvantage 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

Cyberknife Vs Gamma-Knife Vs X-Knife:CK: Accuracy similar with Gamma-Knife

Treatment delivery accuracy: GK: ~1 mm

CK : ~1 mmLA based SRS: 1-2 mm (iso-

centric inacurracy; LUTZ test)

PTV margin:CK: <1 mmGK: <1 mmLA based SRS: 1-2 mm GK/CK LA based SRS

CK has the accuracy of GK and flexibility of LA based SRS

fSRSExtended 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

Volumetric Modulated Arc Therapy

• Rotational IMRT Technique.• Highly conformal dose distribution with better

sparing of OAR.• Dose Modulation: Gantry movements, dose

rate, beam aperture.• Shorter treatment time and MU.• SRS & SBRT for cranial and body lesions.

Medical Dosimetry 40 (2015) 3–8

SRS and Brain Metastases:Current Status:• SRS is highly effective in local control of single and

multiple metastatic lesions.• Even for radioresistant tumors (melanoma &

Kidney).• No technical superiority.• Doses usually > 18 Gy in single sessions.• Lesions > 8 – 10 cc Resection first.• GK is equally effective as surgery for smaller lesions.• Re-irradiation is possible.

B. Lippitz et al. / Cancer Treatment Reviews 40 (2014) 48–59

SRS and Brain Metastases:Current Status:

Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 710e717, 2015

Patients < 50 Years and 1 – 4 lesions Survival advantage for SRS alone, with no effect on distant brain relapse.

SRS and Brain Metastases:Current Status:

Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 710e717, 2015

Take Home Message:

• The art of RS is continuously evolving.• Better understanding of radiobiology.• Better technologies of radiation therapy

delivery.• The conventional approach for management

of metastatic brain disease has been changed dramatically in the past 2 years WBRT can be omitted in selected patients.

Thank You