This document discusses refinements in the art of radio surgical treatment of cranial lesions. Key points include: 1) Improvements in neuroimaging, neuroanatomy knowledge, and radiation therapy delivery systems have enhanced radio surgical treatments. 2) A better understanding of radiobiology, such as the 5 R's of radiobiology and effects of single high doses, has provided new insights. 3) Technologies like Gamma Knife, CyberKnife, and linear accelerator-based systems have expanded indications for radio surgery to include larger and extracranial lesions through fractionation.

1. Radio surgical treatment of cranial
lesions; Refining the art
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Kasr Al-Aini School of Medicine
Cairo University.

2. 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).

3. 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.

4. 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.

5. • 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 SRS
Radiobiological Complexity of
Cranial Targets:
International Journal of Radiation Oncology Biology Physics, vol. 25, no. 3, pp. 557–561, 1993.

6. New Insights of SRS
Radiobiological Complexity of Cranial
Targets:
Cancer Treatment Reviews 37 (2011) 567–578

7. Gamma-Knife
LAbased SRS Systems
BrainLAB
Novalis
Trilogy
Tomotherapy
CyberKnife
Radiosurgery Tools:

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

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

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

11. ‘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

12. 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

13. Cyberknife Vs Gamma-Knife: Dissimilarity
GK 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
Planning
Planning method
No complex planning
Simple
Inverse planning
Complex
Isodose prescription
Fractions
Tumour size
Usually 50%
Single
Only smaller lesions can
be treated
Usually 80-95%
May treat multiple fraction
Larger lesions also can be
treated in fractionated
schedule
Electricity
Possible
Energy source
Verification
Radiation
Not possible
GK can work with less electricity
Even Intra-fraction movement can
be corrected
CK more economicalIndications Only brain lesions Both extra & intra cranial

14. 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

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

16. 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

17. 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

18. 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

19. SRS and Brain Metastases:
Current Status:
Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 710e717, 2015

20. 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

21. 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.

22. Thank You