1. SRS 2013

2. Leaning objectives Available teqs. Radiobiology. Review the clinical use. Side effects. Planning evaluation.

3. STEREOTACHTIC STEREO:FROM GREEEK WORD STEREO MEANING SOLID AS IN 3D TACHTIC: ARRANGEMENT,ORIENTATION

4. RADIOSURGERY: High dose Radiation delivered in generally one fraction. Considered ablative. Generally yields high rate of local control.

5. Modern definition The delivery of stereotactically directed, highly focal, large single dose of radiation to inactivate tumor growth or obliterate a vascular lesion. (ASTRO 2009).

6. Developed by, Lars Leksell a neurosurgeon in late 1940s Using Protons, Leksell and larsson studied SRS on humans and animals in Uppsala, Sweden 1950s Developed gamma knife in 1960s.

7. Basic Principles Inverse relationship between dose and volume to respect tolerance. Thus larger target volume must receive lower dose Lower dose=Lower probability of obliteration or tumor control larger single dose damaging to late responding tissue

8. Radiobiology Treat with larger single fraction of radiation 1- The radiobiological response of benign tumors and vascular lesion is closer to the surrounding normal tissue than malignant tumor. 2- High dose single fraction works better in malignant tumor than previously believed. (effect on vasculature) 3-By treating tumor with no extra margin, you can give higher dose of radiation Improved conformality by piecemeal irradiation Radiosurgery can replace surgical intervention

10. A classic example of in vivo Chinese Hamster cell survival illustrating the linear tail (on a log-linear plot) of the cell survival curve at high dose where cell killing becomes purely exponential.

11. Effect of single dose on low and high α / β Comparison of single-dose effect curves (A) and fractionated dose-effect curves (B) for low and high α / β tissues. The small advantage seen in the low-dose region sparing low α / β tissues (A) is amplified through dose fractionation (B).

13. SRS delivery system Gamma Knife Linear Accelerator 1-Standared Linac. 2-Cyberknife. 3-Tomotherapy. 4-Rapid Arc. Charged particle 1-Protons. 2-Carbon Ions.

14. Gamma- Knife Cone-BaseMLC Based RadiationNuclearLinac Dose Prescription to Periphery of Target 50% Isodose70-90%Isodose Usually 80% Dose Homogeneity Peripheral dose =50% of max dose Peripheral dose 70-90% of max dose ConformalityGamma-Knife better than cone based Linac treatment Comparable to Gamma- Knife

15. Linac Vs Gamma Periphery dos =50% Maximal dose=100% Periphery dos =80%

16. Dose delivery SRS dose is prescribed to isocenter as well as to tumor periphery. Tumor periphery dose often quoted as percent of maximal dose e.g. (tumor completely covered by 80% isodose line). Dose at the target periphery is the clinically relevant dose, since this generally reflects the minimum dose delivered to the target. Peripheral dose 50-80% Central dose 100%

17. SRS Plan Evaluation 100% target coverage is desirable. RTOG:Entire target must be covered by 90%

18. Why 80%

19. SRS plan evaluation PI/TV=planning isodose volume to target volume ratio PI/TV=Radiation dose volume/taget volume Ideal conformity PITV=1.0 PI/TV<2.0 meets RTOG SRS guidelines Rule of thumb PITV=1.2 is good

20. HI= D max ⁄ D Rx ≤ 2 Acceptable <3.5.

21. SRS needs steep dose gradient out side of the target Better than 60% per 3 mm. Generally we worry about distance between prescription isodose shell and 1/2of prescription isodose shell

22. What is treated with SRS? Brain metastasis <4 cm as a boost or salvage Primary brain malignancy <4 cm. generally as a boost or salvage Acoustic neuroma <3 cm. Menengioma <3cm. Pitutary adenoma residual or recurrent. Arteriovenous malformation. Trigiminal neuralgia(target is verve root). Parkinson’s disease and sezures.

23. Think About Irradiate the target safely Ablate the tumor/target. Minimize the risk of toxicity to normal organ. Relevant Variables: Dose Volume Location/neighboring critical structures

24. What are the critical structures Brain Stem Normal Brain Tissue Hippocampus temporal lobes Insula Motor cortex Language area Cranial Nerves Cochlea

25. Review the literature Mostly retrospective Single institution Late toxcicity.

26. SRS Toxicities Acute(1-2%) Sezures mostly occures in the first 24 h (cortial structure, prior sezures, anti epileptic medications H/A, nausea, vomiting, aphasia, motor neuropathy Late: Radiation necrosis(2-3%) 2ndy malignancy Death extremely rare

27. Optic Nerve and Chiasm Cavernous sinus meningiome

28. Pituitary adenoma

29. Risk of Optic Neuropathy Max ose<88101215>15 U.Pitt0% (0/35) 24% (4/17) U.Pitt0% (0/31) 67% (2/3) k.Franzen.U 27% (6/22)78% (9/13) U.Pitt1 case3 cases of 2400 Mayo clinic2% (1/58) 7% U.Maryland0% (0/20) Acturial incidence @3 years SRS=Fractionated RT in case of Optic neuropathy Tishler et al, IJOBP 27 215-21,1993 Duma et al, Neurosurgery 32:699-740,1993 Girkin et al, Opthalmology.104 1634-43,1997 Leber et al,J. Neurosurgery.88:43-50,1998tishle Stafford et al IJOROBP 55:1177-81,2003 Ove et al.InT J Cancer9 90:343-50,2000 Shrieve et al, J neurosurgery S3:390-5,2004

30. Radiation induced Optic Neuropathy occurs with in 3 years after SRS. Is Rare. No Dose constrains based upon: length of optic nerve Volume of Optic apparatus Location along the nerve Prior external beam Combined illness

31. Which one is safer?

32. Uncertanity ? DVH what parameter we should use to predict toxicity. Precision of contouring. Regional variation in dose suitability volume of the nerve? prepheral vs central? Chiasm versus nerve?

33. Hearing Date from retrospective studies of benign tumors (Aquestic neuroma, cerebello- pontine angle meningioma) Hearing loss associated with the dose prescribed to the tumor periphery

34. Hearing Relevant Questions Is hearing loss from: 1-Radiation effect of the nerve VIII? 2-Radiation effect of vasculature of the nerve? 3-Radiation effect on the brain stem? 4-Radiation effect on the cochlea? 5-Tumor effect

35. Hearing Relevant variables impacting risk of hearing loss 1-Tumor related Size Location (intra-canlecular Vs CP angle) 2-Patient related Age Pretreatment hearing status. 3-Treatment related variables Dose Volume 4-Assement related variables Frequency of hearing assessment

36. Hearing Loss : acoustic neuroma dose Peripheral dose <88101215>15Gy U.Pitt5 year preserved hearing =75% 5year survivable hearing is 95% 50 * 60% * Komak iCityHearing preservation=68%13% # U.Pitt10 years5 year preserved hearing =44% 10year survivable hearing is 85% * SRS dose de-escalation 18-20 Gy to 16-18 to 14-16. # p=<.001

37. Hearing outcomes after Stereotactic Radiosurgery for unilateral shwannoma (IJORO,2013 seol national university) 60 patients tumor in the canal All treated with RT as initial treatment All patients treated with cyberknife Max dose to tumor 24.3 Gy Marginal dose 12.2Gy Isodose line used 50% Maximal dose to chochlea 8 Gy and mean is 4.2Gy. Acturail hearing loss 70,63 and 55 at 1,2 5 years.

38. Hearing :Cochlea Dose Stable/improved vs. worse hearing 1-median cochlear dose 3.7 vs. 5.3, p=0.0005 in 82 patients 2-lower radiation dose to cochlea volume over range of 2-11Gy, P=0.0001 Messager et al.J.neurosurg.107:733-9,2007 U.Hospital Erasme,Belgium 3-cochlear point dose 4.6 vs 4.8 (NS) in 175patients Gabertet al. Neurochirurgie 50:350-7,2004 U.de latimon,France 4-cochlear max 9.1vs 7.8 (NS) in 25 patients Peaket al.cance 104:580-90, seol,France,205

39. Hearing loss FSRT vs SRS Between 97-2008 42 patients Dose is 54 Gy/27-30 Acturial Tumor control at 2, 4,10 were 100,91,85% Servivable hearing loss at 2 years almost 50 % and reaching to 100%by 10 years.

40. To improve Hearing Prescribe marginal dose of 12-13Gy Contour brain stem Contour cochlea Delineate tumor and nerve exclude Viii from GTV.

42. CT images of normal right inner ear anatomy: (a–f) axial superior to inferior images. 1, internal auditory canal (IAC); 2, superior semicircular canal (SCC); 3, lateral SCC; 4, posterior SCC; 5, vestibule; 6, basal turn of cochlea; 7, apical turn of cochlea; 8, vestibular aqueduct; 9, facial nerve.

44. Figure 3fNormal anatomy of the temporal bone. Axial high-resolution (a–e) and coronal MPR (f) multidetector CT images of the temporal bone show the external auditory canal (EAC), carotid canal (CC) and jugular bulb (JB), malleus (M), facial nerve (FN), cochlea (C), semicircular canals (SCC), internal auditory canal (IAC), incus (I), vestibule (V), vestibular aqueduct (VA), and mastoid air cells (MAC).

45. Trigeminal and facial nerve Variables impacting CN V and VII toxicity Prescribed Radiation Dose length and volume of nerve irradiated modern imaging prior resection Brain Stem maximal dose

46. Trigeminal and facial Nerve University of Florida retrospective study of 149 patients treated with SRS for AN 1- Prior SX confined to 5 folds increased in toxicity. 2-Brain stem Maximum dose p<0.0001 BS max dose > 17.5 Gy resulted in 50 fold incresed risk 3- Univariate analysis CN V, VII significant for the nerve length.

48. Brain Stem Accepted dose 10-12 Gy max,(Loffler NSJ 2008). Confounding factors Tumor type Regional variation

49. Brain Stem Retrospective study of 38 patients SRS for Benign and low grade lesions 7 developed adverse radiation imaging effect 4 new neurologic deficits 3 no neurologic deficits 3 developed permanent neurologic defecits Sharma et al.Neurosurgery J,U.Pitts 2008

50. Thank you