12.06.2015 Frank Zimmermann
Room Clio, 10:00 – 11:00 am
Klinik für Strahlentherapie und Radioonkologie
15th EURETINA Congress, Nice
Stereotactic Radiotherapy for Wet AMD using micro-collimated low-voltage X-ray:
Mechanisms and Synergy with anti-VEGF
Klinik für Strahlentherapie und Radioonkologie
Therapeutic approaches
• Local Anti-VEGF injections o Lucentis® o Avastin® o Macugen® o Eylea®
• Photodynamic / Laser therapy
• Radiation therapy
• Combined radiation therapy and Anti-VEGF
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – vascular effect in tumors
With single doses beyond 12 Gy, vascular effects by obliteration is dominant Song CW et al. Technical Basis of Radiation Therapy 2012
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – vascular effect in AVM
Regions of vascular constriction due to abnormal proliferation of surviving endothelial cells: hyaline and calcium deposits, thrombosis – obliteration in 80 % Single doses of > 16 Gy and smaller volumes with better results Levy RP et al. Neurosurg Clin N Am 1990; Andisheh B et al. J Neurosurg 2009
Klinik für Strahlentherapie und Radioonkologie
Results from radiosurgery: vascular malformation
Obliteration and reduced risk from AVM with 17.5 – 25 Gy
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – results from trials on AMD
Conflicting interpretation Best-corrected visual activity loss vs. reading ability vs. improved vision vs. visual acuity stabilization vs. daily living tasks dependent on vision vs. SF-36 questionaire Different techniques and poor precision in some techniques high energy photons, protons, brachytherapy Different concepts Single doses of 1 – 4 Gy, total doses 7.5 – 24 Gy, or HDR 12 – 15 Gy Rbrady et al. IJROBP 1997; RAD Study Group, Ophthalmology 1999; Bergink et al. Graefe’s Arch Clin Exp Ophthal 1998; Valmaggia et al. Am J Ophthalmol 2002; Evans et al. Cochrane Coll 2010; Dugel et al. Opthalmology 2013; Kishan et al. IJROBP 2013; van Houtte et al. Cancer Radiother 2014
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – results from trials on AMD
Different indications wet and/or dry macular degeneration, different disease extent Side effects no retinopathy, no optical neuropathy, no malignancy, but 15 % mild retinopathy at 5 years Small, non-significant advantage in favour of treatment, but biased for non-blinded trials Short follow-up !!!
Rbrady et al. IJROBP 1997; RAD Study Group, Ophthalmology 1999; Bergink et al. Graefe’s Arch Clin Exp Ophtahl 1998; Valmaggia et al. Am J Ophthalmol 2002; Trikha et al. Retina 2011; Dugel et al. Opthalmology 2013; Kishan et al. IJROBP 2013; van Houtte et al. Cancer Radiother 2014
Klinik für Strahlentherapie und Radioonkologie
Risk in radiation therapy – results from high doses
With doses beyond 20 Gy: focal area of photoreceptor loss and retinal pigment epithelial atrophy
Trikha et al. Retina 2011
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – biological rationale
Regression and inactivation of subretinal neo-vasculature Reabsorption of fluid and blood Reducing the risk of further leakage and bleeding Causing subretinal fibrosis and vascular obliteration
Brady et al. JROBP 1997
Klinik für Strahlentherapie und Radioonkologie
Why radiation therapy – biological rationale
Comparison of biological efficacy - 4 x 4 Gy in 4 minutes each - 12 Gy in 11 minutes - 16 Gy in 4 minutes For α/β-value of 4 Gy for vessels range from 30 – 100 Gy Need for risk reduction for late effects by high precision If RT, than precise with ~ 16 Gy
Klinik für Strahlentherapie und Radioonkologie
Why combined therapy – clinical rationale
The EXCITE Study - Phase-III-randomized trial - 353 patients - After 3-months: monthly > quarterly injections at 12
months Side effects (EXCITE and SUSTAIN studies): - 12 % conjunctival hemorrhage - 15 % eye pain - 7 % increased intraocular pressure - 1 % retinal hemorrhage Schmidt-Erfurth U et al. Ophthalmology 2011; Holz FG et al. Ophthalmology 2011
Klinik für Strahlentherapie und Radioonkologie
Greec στερεός stereós: „rigid, fix, constant, 3 dimensions“ τάξις táxis: „disposition, installation, arrangement“
Definition: Precise technique for small target area and steep dose decrease for optimal normal tissue protection
Stereotactic radiation therapy – new concept
Klinik für Strahlentherapie und Radioonkologie
High single dose Aim: strong local tissue reaction and small vessel obliteration by
endothel proliferation with fibrosis High precision 3D-coordinate system with high precision ( error < 1 mm ) Image / camera control to verify the precision Exact, robust and reproducible patient positioning and navigation
of the beam
Short treatment Only 1 session
Definition and prerequisite: radiosurgery ( single fraction stereotactic radiation therapy )
Klinik für Strahlentherapie und Radioonkologie
Quality assurance of stereotactic radiation therapy
3 robotically positioned 100 kV photon beams Test with modern algorithm in bulbus sizes of 20 – 28 mm Doses to - Lens - Optic nerve - Distal tip of central retinal artery - Retina outside target volume - Ciliary body
No significant variations: doses below critical levels !
Cantley J et al. Phys Med Biol 2013
Klinik für Strahlentherapie und Radioonkologie
Adjustment of the patients head
Klinik für Strahlentherapie und Radioonkologie
Quality assurance of stereotactic radiation therapy
Eye stabilization
Taddei PJ et al. Phys Med Biol 2010
Klinik für Strahlentherapie und Radioonkologie
Fine adjustement of the I-Guide
Klinik für Strahlentherapie und Radioonkologie
Quality assurance of stereotactic radiation therapy
Beam orientation Virtual dose distribution
Taddei PJ et al. Phys Med Biol 2010
Klinik für Strahlentherapie und Radioonkologie
Quality assurance of stereotactic radiation therapy
Dose distribution with 24 Gy
Hanlon J and Lee C American Ass Phys Med 2009; Moshfeghi DM et al. Br J Opthalmol 2011
Klinik für Strahlentherapie und Radioonkologie
Quality assurance of stereotactic radiation therapy
Dose distribution with 24 Gy
Hanlon J and Lee C American Ass Phys Med 2009
Klinik für Strahlentherapie und Radioonkologie
Prerequisite for intervention
Clear patient selection: - Actively leaking - < 4 mm
Extensive explanation also about alternatives Explanation of risk: early and late effects in detail
Jackson TL et al. Retina et al. 2015
Klinik für Strahlentherapie und Radioonkologie
Clinical effect
Pretreatment Intervall of injections: 4 weeks After 12 months Intervall of injections: 8 weeks
Klinik für Strahlentherapie und Radioonkologie
High biological effect Close interaction with anti-VEGF High precision / safety Comfortable, non-invasive treatment
The new aspects
Klinik für Strahlentherapie und Radioonkologie
Open for questions !
Merci beaucoup de votre attention
… questions?
12.06.2015Frank Zimmermann��Room Clio, 10:00 – 11:00 amTherapeutic approaches�Why radiation therapy – vascular effect in tumorsWhy radiation therapy – vascular effect in AVMResults from radiosurgery: vascular malformationWhy radiation therapy – results from trials on AMDWhy radiation therapy – results from trials on AMDRisk in radiation therapy – results from high dosesWhy radiation therapy – biological rationaleWhy radiation therapy – biological rationaleWhy combined therapy – clinical rationaleStereotactic radiation therapy – new conceptDefinition and prerequisite: radiosurgery �( single fraction stereotactic radiation therapy )Quality assurance of stereotactic radiation therapyAdjustment of the patients headQuality assurance of stereotactic radiation therapyFine adjustement of the I-GuideQuality assurance of stereotactic radiation therapyQuality assurance of stereotactic radiation therapyQuality assurance of stereotactic radiation therapyPrerequisite for interventionClinical effectThe new aspectsOpen for questions !��Merci beaucoup de votre attention
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