SRS/SRT in Vicinity to Anterior Optic Pathway

Transcription

1 SRS/SRT in Vicinity to Anterior Optic Pathway Vladyslav Buryk, Maris Mezeckis, Dace Saukuma, Jelena Nikolaeva, Indra Surkova, Galina Boka, Maris Skromanis Stereotactic radiosurgery center Sigulda, Latvia Visual Pathway Optic Nerves Optic Chiasm Optic Tracts Lateral Geniculate Nucleus Optic radiations Primary visual cortex 1

2 Optic Nerves Optic Chiasm Optic Tracts Lateral Geniculate Nucleus Optic radiations Primary visual cortex pathology visual field assessment 2

3 neighboring structures Anteriorly : ACA and their communicating artery Posteriorly: pituitary gland stalk, hypothalamus Superiorly: 3 rd ventricle Inferiorly: Sphenoid Sinus, Pituitary gland Laterally: Cavernous Sinus, CN III, IV, V1, V2, VI, ICA pathology tumors of the eye globe/ uveal melanoma, retinoblastoma orbital tumors tumors of the optic canal, superior orbital fissure and sphenoid wing, sella turcica, ACF, MCF 3

4 pathology tumors of the eye globe orbital tumors/ optic nerve sheath mеningioma, optic nerve glioma, metastases, cavernoma tumors of the optic canal, superior orbital fissure and sphenoid wing, sella turcica, ACF, MCF pathology tumors of the eye globe orbital tumors tumors of the optic canal, superior orbital fissure and sphenoid wing, sella turcica, ACF, MCF: pituitary adenoma, meningioma, metastases, craniopharyngeoma, chiasmatic glioma, hamartoma 4

5 pathology clinical symptoms Visual acuity impairment Ophtalmoparesis Exophtalmus Headache Hypopituitarism Trigeminal neuralgia Epileptic seizures Neurological deficits are usually present in up to 70 % of patients with skull base tumors as a consequence of tumour growth or previous surgery, and are mainly represented by deficits of cranial nerves II VI Multiplanar Sagital and Coronal Small FOV cm 2-3 mm slice T1W, T2W Post T1W + FS Dynamic enhanced for pituitary lesions pathology MRI diagnostic 5

6 pathology CT diagnostic hyperdense with well-defined margins arising from the dura uniformly enhancing hyperostosis (thickening and sclerosis) of the contiguous bone dense calcification in particular at the tuberculum sella AVP and pathology contour 6

7 AVP and pathology contour pathology treatment Radiation treatment Surgery Chemotherapy (lymphoma, mts) Multidisciplinary approach neurosurgeon, neuro/ophtalmologist, ENT, radiation oncologist, oncologist, endocrinologist 7

8 Distant RT External beam radiation therapy (EBRT) (FCSRT, IMRT, VMAT) Particle Therapy (proton therapy, boron neutron capture therapy(bnct)) Stereotactic Radiosurgery (SRS/FSRS) single fraction SRS hypofractinated FSRS Local RT Brachytherapy/UM palladium-103, ruthenium/ intracavity yttrium-90,p32(cranipharyngioma) pathology treatment Radiation treatment Goals of RT: Locoregional tumor control Normal structures and tissues protection 8

9 pathology treatment Radiation treatment Goals of RT: Locoregional tumor control Normal structures and tissues protection radiation treatment toxicity optical apparatus post radiation toxicity brain tissue necrosis pituitary deficits with neuroendocrine disorders cognitive and memory deficits 9

10 radiation treatment toxicity optical apparatus post radiation toxicity brain tissue necrosis pituitary deficits with neuroendocrine disorders cognitive and memory deficits radiation treatment toxicity optical apparatus post radiation toxicity (eye, retina, optic tract) ACUTE Radiation Morbidity (3 month) Grade 1 Grade 2 Grade 3 Grade 4 Mild conjunctivitis w/ or w/o scleral injection increased tearing Moderate conjunctivitis w/ or w/o keratitis requiring steroids and/or antibiotics dry eye requiring artificial tears iritis with photophobia Severe keratitis with corneal ulceration / objective decrease in visual acuity or in visual fields / acute glaucoma / panophthalmitis Loss of vision (uni or bilateral) 10

11 radiation treatment toxicity optical apparatus post radiation toxicity(eye, retina, optic tract) LATE Radiation Morbidity Grade 1 Grade 2 Grade 3 Grade 4 asymptomatic cataract minor corneal ulceration or keratitis symptomatic cataract moderate corneal ulceration minor retinopathy or glaucoma severe keratitis severe retinopathy or detachment Panophthalmitis / blindness Radiation-induced optic neuropathy RION radiation treatment toxicity Radiation-induced optic neuropathy/rion sudden, painless, monocular visual loss from 3 months to more than 8 years (or longer) after radiation exposure majority of patients develop symptoms within 3 years after RT, with peak incidence at 1 to 1.5 years severe loss to the level of no light perception occurs in 45% with up to 85% risk factors: dose, compression, previous RT, CHT, diabetes, acromegaly 11

12 radiation treatment toxicity Radiation-induced optic neuropathy/rion Multifactoral: optic nerve ischemia (vascular endothelium damage) and neuroglial cells damage anterior RION: orbital and intraocular lesions(distal to lamina cribrosa (head of optic nerve, prelaminar part ON) posterior RION: retrolaminar (more common) Lesions anterior to the chiasm will affect the ipsilateral eye Lesions of the chiasm will affect the bilateral temporal visual fields Lesions posterior to the chiasm will affect visual fields in both eyes radiation treatment toxicity Radiation-induced optic neuropathy/rion Multifactoral: ischaemic demyelination, reactive astrocytosis, endothelial hyperplasia, obliterative endarteritis, fibrinoid necrosis anterior RION: pale OD edema with incidental splinter hemorrhages. posterior RION: no OD edema, visual fields deficits. Lesions anterior to the chiasm will affect the ipsilateral eye Lesions of the chiasm will affect the bilateral temporal visual fields Lesions posterior to the chiasm will affect visual fields in both eyes 12

13 radiation treatment toxicity Radiation-induced optic neuropathy/rion radiation treatment toxicity Radiation-induced optic neuropathy/rion 13

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16 External beam radiation therapy (EBRT) The Emami (1991) data for dose: 5% risk for 50 Gy/ tolerance dose for chiasm, optic nerves of toxicity in 5 years (TD 5/5) 50% risk for 60Gy/ tolerance dose for chiasm, optic nerves of toxicity in 5 years (TD 50/5) Emami B, et al: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21(1): , 1991 QUANTEC (2010) data estimates the risk of TX optic nerve/chiasm Maximum point dose (Dmax) < 55 Gy < 3% Gy 3%-7% >60 Gy >7%- 20% 16

17 Parsons (1994), 131 patients/ EBRT for H&N tumors 5 patients anterior RION/ 12 patients retrobulbar RION The 15-year risk of radiation-induced optic neuropathy (RION) No injuries were observed in total dose of < 59 Gy. 11% with doses >60 Gy, dose fractions of less than 1.9 Gy 47% with doses >60 Gy, dose fraction size was greater than or equal to 1.9 Gy 17

18 Risk factors Age: Parsons et al. reported an increased risk of RION with increasing age y.o. > 60 Gy none RION 50-70y.o. > 60 Gy 26% RION >70 y.o. > 60 Gy 56% RION Re-irradiation: Flickinger et al. 1 of 10 patients: RION initial 40 Gy/ 7.5-year interval/46 Gy; both at 2 Gy/fractions Data on other clinical factors such as chemotherapy, diabetes mellitus, and hypertension have been inconsistent. Risk factors Tolerance might be lower in patients with pituitary tumors. Complications at doses as low as 46 Gy at 1.8 Gy/fraction have been reported Mackley (2007) et al. constrained the optic structure Dmax to 46 Gy Mackley HB, Reddy CA, Lee SY, et al. Intensity-modulated radiotherapy for pituitary adenomas: The preliminary report of the Cleveland Clinic experience. Int J Radiat Oncol Biol Phys 2007;67: van den Bergh (2003) et al. constrained the optic structure Dmax to 45 Gy van den Bergh AC, Dullaart RP, Hoving MA, et al. Radiation optic neuropathy after external beam radiation therapy for acro- megaly. Radiother Oncol 2003;68: The RION latency was shorter in patients with pituitary tumors 10.5 vs 31 months (range, 5 168) in patients with pituitary targets and nonpituitary targets, respectively 18

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20 Radiation treatment Stereotactic Radiosurgery (SRS/FSRS) Radiosurgery high dose, high precision radiotherapy where whole prescribed dose is delivered in single/few(up to 5) fraction > 8 Gy for 1 fraction or total for BED> 100 Gy high dose gradient tumor / normal tissues from 1 to 5, in some cases up to 8 fractions for a short treatment time 20

21 Historically, Single fr. SRS (Dmax) limit to the AVP 8 Gy(<10 Gy) Single fr. SRS doses that control benign tumors (13-16 Gy), At this dose, risk of blindness as high as 27% has been reported Leber KA, Bergloff J, Pendl G: Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 88(1):43-50, 1998 Historically, Single fr. SRS (Dmax) limit to the AVP 8 Gy(<10 Gy)/level III evidence/ Tishler RB, Loe er JS, Lunsford No. of LD, Prescription et al. Tolerance doseof cranial Dmax nerves to of OAthe cav- ernous Visual sinus decline to rate study patients (range,gy) (range,gy) (%) radiosurgery. Int J Radiat Oncol Biol Phys 1993; 27: Tishler et al (1993)* 62/ <8 Gy 8-10 Gy/ >10 Gy 0 4pts/ 24% Leber et al(1998)** 45 14,3( ) <10 Gy Gy >15 Gy 0 26,7% 77,8% *Tishler RB, Loe er JS, Lunsford LD, et al. Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat Oncol Biol Phys 1993; 27: **Leber KA, Bergloff J, Pendl G: Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 88(1):43-50, 1998 Jason P. Sheehan and Zhiyuan Xu Optic Apparatus Tolerance Up to 8 Gy Sheehan and Gerszten, Controversies in Stereotactic Radiosurgery: Best Evidence Recommendations, 2014 Thieme Medical Publishers 21

22 SRS recent studies/dose escalation level III evidence/ study No. of patients Prescription dose (range,gy) Dmax to OA (range,gy) Staffort et al (2003)* (12-30) Gy <8 Gy 8-10 Gy Gy (no EBRT) >12 Gy Visual decline rate (%) 1,7%(0% no EBRT) 1,7%(0% no EBRT) 0 6,9% (3% no EBRT) * Stafford SL, Pollock BE, Leavitt JA, et al. A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2003; 55: John C. Flickinger, Douglas Kondziolka, and L. Dade Lunsford/ Optic Apparatus Tolerance Greater than 8 Gy/ Sheehan and Gerszten, Controversies in Stereotactic Radiosurgery: Best Evidence Recommendations, 2014 Thieme Medical Publishers 1.1% RISK RION for patients receiving up to 12 Gy to the optic apparatus SRS recent studies/dose escalation Mayo Clinic reported on 88 patients treated with SRS for skull base meningiomas, with no RION at a median Dmax of 10 Gy (range: 1-16 Gy) Morita A, Coffey RJ, Foote RL, et al: Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: 222 patients treated with SRS for perioptic tumors, 1 developed unilateral blindness after receiving a Dmax of 12.8 Gy, these results, support the concept that small portions of the AVP (2-4 mm 3 ) can safely receive radiation doses up to 12 Gy with a low risk of RION. Leavitt JA, Stafford SL, Link MJ, et al: Long-term evaluation of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 87(3): ,

23 SRS recent studies/dose escalation Pollock(2014), Among 133 treated patients who had not received previous irradiation, with a total of 266 anterior visual sides analyzed, 29 anterior visual pathways (11%) received a maximum dose of greater than 12 Gy, and no RION occurred with a 95% CI risk of optic neuropathy of 0%- 13.9% at 12 Gy Pollock BE, Link MJ, Leavitt JA, et al: Dose-volume analysis of radiation- induced optic neuropathy after single-fraction stereotactic radiosurgery. Neurosurgery 75(4): , 2014; [discussion 460] recent review of radiation dose-volume effects of the optic structures, QUANTEC(2010) threshold limits for single-fraction SRS 12 Gy Fractinated SRS studies: Adler (2006), 49 patients with perioptic tumors treated with fsrs showed excellent tumor control and visual field preservation at mean follow-up of 49 months, with 94% tumor control and 1 patient (2%) experiencing RION Adler Jr JR, Gibbs IC, Puataweepong P, et al: Visual field preservation after multisession Сyberknife radiosurgery for perioptic lesions. Neurosurgery 59(2): , 2006; [discussion ] Killory (2009), 20 patients treated with SRS for perichiasmatic pituitary adenomas who received 25 Gy in 5 fractions, vision remained intact in all patients and improved in 3 patients Median maximum chiasm dose was 23.3 Gy (range: Gy) Killory BD, Kresl JJ, Wait SD, et al: Hypofractionated CyberKnife radiosurgery for perichiasmatic pituitary adenomas: Early results. Neuro- surgery 64(suppl 2):A19-A25,

24 Fractinated SRS studies: Liao (2014) excellent results were reported in a series of patients treated for pituitary adenomas close to the optic apparatus to 21 Gy in 3 fractions, with dose to the optic apparatus reported as mean dose of 16.7 Gy to the nerve and 14.6 Gy to the chiasm. Liao HI, Wang CC, Wei KC,et al: Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus. J Clin Neurosci 21(1): , 2014 Minniti et al.(2014), also report outcomes after fsrs for patients with skull base metastases involving the anterior visual pathway who received 25 Gy in 5 fractions, and found a 2-year local control of 72%, with no RION and 51% of patients having improvement of preexisting cranial nerve deficits. Minniti G, Esposito V, Clarke E, et al: Fractionated stereotactic radio- surgery for patients with skull base metastases from systemic cancer involving the anterior visual pathway. Radiat Oncol 9:110, 2014, 24

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27 Patient selection: not available for NS, residual, recurrent tumor Targer identification: CT, MRI with contrast Dose: RT 1,8 Gy/ 45Gy-54Gy-60Gy /25-30 fr Dmax:1,8Gy/<60Gy SRS Gy (>3 mm from chiasma/nerve, D<3 cm) fsrs 5-8 Gy/18-25 Gy/ 3-5 fractions Dose tolerance limits for optic pathways a less than 1% incidence of RION an optic apparatus maximum point dose/dmax 1 fr/12gy 3 fr/19.5gy 5fr/25Gy risk 1%HRL D50% 1fr 6,5Gy 3fr/10Gy 5fr/12Gy Material and Methods: there were treated 18 patients with tumors in the area of the optical path in SRC "Sigulda" from Among them, 11 patients with meningioma, 5 patients with pituitary adenoma, 1 with cranipharyngioma, 1 recurrent anaplastic V nerve neurinoma. Patients had CyberKnife M6 SRS treatment at doses ranging from 2100cGy to 2500 cgy in 3-5 fractions. All patients received doses with regard to tolerance adjacent normal critical structures. 27

28 X-RAY ROBOT SYNCHRONY LINAC TREATMENT CONTROL SYSTEM ROBOTIC DELIVERY SYSTEM X-RAY DETECTOR TREATMENT TABLE CyberKnife M6 SRS/FSRT Cranioorbital meningioma Gr II. St. after NS V=35,9 cc, fsrs 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 20,6Gy 28

29 Cranioorbital meningioma Gr II. St. after NS V=35,9 cc, fsrs 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 20,6Gy Tuberculum sella meningioma. St. after NS V=0,49 cc, fsrs, 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 25,1Gy 29

30 Tuberculum sella meningioma. St. after NS V=0,49 cc, fsrs, 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 25,1Gy D50%=1,76Gy corticotrophic pituitary adenoma. St. after NS(2)+(endovs) V=5,42 cc, fsrs 5,5Gy/4f/22Gy Dmax OCH=17,2Gy LON=17,86Gy RON=11,31Gy 30

31 corticotrophic pituitary adenoma. St. after NS(2)+(endovs) V=5,42 cc, fsrs 5,5Gy/4f/22Gy Dmax OCH=17,2Gy LON=17,86Gy RON=11,31Gy corticotrophic pituitary adenoma. St. after NS(2)+(endovs) V=5,42 cc, fsrs 5,5Gy/4f/22Gy Dmax OCH=17,2Gy LON=17,86Gy RON=11,31Gy 31

32 NF pituitary adenoma V=37,5 cc, fsrs 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 24,34Gy NF pituitary adenoma V=37,5 cc, fsrs 5Gy/5f/25Gy Dmax AVP(CH,LON,RON)= 24,34Gy 32

33 Cavernous sinus meningioma V=19,3 cc, fsrs, 5Gy/5f/25Gy Dmax OCH=25,1Gy LON=25,07Gy RON=14,9Gy Cavernous sinus meningioma V=19,3 cc, fsrs, 5Gy/5f/25Gy Dmax OCH=25,1Gy LON=25,07Gy RON=14,9Gy 33

34 Craniopharyngioma V=4,15 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=24,9Gy D50%=3,81Gy Craniopharyngioma V=4,15 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=24,9Gy D50%=3,81Gy 34

35 Craniopharyngioma V=4,15 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=24,9Gy D50%=3,81Gy After 2 month Meningioma post fsrs(1 year) V1=11,4cc fsrs, 5Gy/5f/25Gy/ 75% isodose Dmax AOP=21,4Gy D50%=3,41Gy 35

36 Meningioma post fsrs(1 year) V1=11,4cc fsrs, 5Gy/5f/25Gy/ 75% isodose Dmax AOP=21,4Gy D50%=3,41Gy Meningioma post fsrs(1 year) V1=11,4cc V=7,71 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=21,4Gy D50%=3,41Gy 36

37 Meningioma post fsrs(1 year) V1=11,4cc V=7,71 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=21,4Gy D50%=3,41Gy Meningioma post fsrs(1 year) V1=11,4cc V=7,71 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=21,4Gy D50%=3,41Gy 37

38 Meningioma post fsrs(1 year) V1=11,4cc V=7,71 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=21,4Gy D50%=3,41Gy Meningioma post fsrs(1 year) V1=11,4cc V=7,71 cc, fsrs, 5Gy/5f/25Gy/ 80% isodose Dmax AOP=21,4Gy D50%=3,41Gy 38

39 Uveal melanoma, V=3,3 cc, SRS, 21Gy/1f/21Gy Dmax LE=26,5Gy OCH=0,9Gy LON=23,5Gy RON= 2,2Gy Uveal melanoma, V=3,3 cc, SRS, 21Gy/1f/21Gy Dmax LE=26,5Gy OCH=0,9Gy LON=23,5Gy RON= 2,2Gy 39

40 results Median observation is 9 months. So first we evaluated the possible acute complications of treatment. Minimal side effects were found during or within a few weeks after completion of treatment mainly in the form of erythema and tearing. In 1 patients with craniopharingioma was worsening of vision 2 month after treatment due to tumor aedema, tumor size reduction was determined in patients with other defined stabilization. Continued growth of the tumor during the observation was not observed. Conclusions perioptic tumors can be safely treated with single-fraction and hypofractionated SRS with excellent local control and a low rate of vision complications multi-centric data provide support for hypofractionated dose constraints for the optic structures as safe guidelines and suggests a less than 1% incidence of RION in group of patients treated with an optic apparatus pathway maximum point dose of 12Gy in 1, 19.5Gy in 3, and 25Gy in 5 fractions. 40

41 Thank you for attention! Stereotactic radiosurgery center Sigulda, Latvia 41