Ophthalmic tumors. Wolfgang Sauerwein
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1 Ophthalmic tumors Wolfgang Sauerwein
2 Today s menu Introduction and some basics on uveal melanoma Brachytherapy for intraocular tumors Proton therapy for intraocular tumors Proton therapy for conjunctival melanoma High energy beams and PBS in ocular tumors? Controversial issues irradiation of retinoblastoma radiotherapy of the orbit in small children Folie Sauerwein PTCOG 53 Shanghai 2014
3 Ophthalmic tumors Rare diseases In Germany 800 new cases per year (>500 of them treated in Essen) What is different to normal radiotherapy? Very small treatment volume (electron equilibrium??) Very close to important functional structures Treated in dedicated centers with different equipment Special techniques are mandatory Folie Sauerwein PTCOG 53 Shanghai 2014
4 Ophthalmic tumors: Target volumes the entire eye (metastases) Localized tumor in the eye (melanoma, retinoblastoma) the retina and the vitreous (retinoblastoma, lymphoma) the orbit (retinoblastoma, melanoma ) others (iris, conjunctiva ) Folie Sauerwein PTCOG 53 Shanghai 2014
5 Ophthalmic tumors: Irradiation techniques Brachytherapy 90 Sr 106 Ru 125 I Folie Sauerwein PTCOG 53 Shanghai 2014
6 Ophthalmic tumors: Irradiation techniques External beam radiotherapy photons et electrons Folie Sauerwein PTCOG 53 Shanghai 2014
7 Ophthalmic tumors: Irradiation techniques External beam radiotherapy protons Folie Sauerwein PTCOG 53 Shanghai 2014
8 Ophthalmic tumors: Irradiation techniques External beam radiotherapy X rays Folie Sauerwein PTCOG 53 Shanghai 2014
9 Brachytherapy INTRAOCULAR TUMORS Folie Sauerwein PTCOG 53 Shanghai 2014
10 Irradiation of a tumor in the eye: uveal melanoma Protection of the optic nerve, the papilla and the macula, the orbit Dose >100 Gy Techniques - brachytherapy using radioactive plaques - protons Folie Sauerwein PTCOG 53 Shanghai 2014
11 Survival rate Chromosome 3 status predicts survival Tumour related survival of 374 enucleated patients ( ) Tumors with partial monosomy 3 Tumors with disomy 3 AI monosomy 3 Folie Sauerwein PTCOG 53 Shanghai 2014 Months after treatment of the primary tumour
12 Metastases in uveal melanoma risk factors genetics localization size extra-ocular growth Folie Sauerwein PTCOG 53 Shanghai 2014
13 Ru-106 plaques -irradiation with a background of /Bremsstrahlung maximal energy of rays: 3,53 MeV half-life: 366 days steep dose gradient: in 6 mm depth ~ 10% of dose rate at the surface big choice of different applicators prescribed dose: at the sclera 700 ( )Gy at tumor apex >130 Gy indicated for tumors 6 mm height Folie Sauerwein PTCOG 53 Shanghai 2014
14 Ru-106 plaques Folie Sauerwein PTCOG 53 Shanghai 2014
15 I-125 plaques Photon irradiation mean energy kev Half life: 60 days in mm depth 10% of dose rate at the surface Plaques have to be produced at the hospital (8-12 seeds/plaque) Prescribed dose: at the sclera 300(- 500 )Gy at tumor apex >80 Gy Indication for tumors 8-12 mm height Folie Sauerwein PTCOG 53 Shanghai 2014
16 I-125 plaques plaque in stainless steel with Persepex inlay Folie Sauerwein PTCOG 53 Shanghai 2014
17 I-125 / Ru-106 bi-nuclide-plaque Folie Sauerwein PTCOG 53 Shanghai 2014
18 Dosimetry for b-emitters Relative dosimetry difficult but we know how to do Absolute dosimetry real challenging only feasible together with the national standard laboratories (PTB, NIST) Folie Sauerwein PTCOG 53 Shanghai 2014
19 Dose distribution of a 106 Ru-plaque tumor: 8 mm dose: apex: 100 Gy base: 2200 Gy sclera opposite: 1Gy Folie Sauerwein PTCOG 53 Shanghai 2014
20 Dose distribution of a 125 I-plaque tumor: 8 mm dose: apex: 100 Gy base : 440 Gy sclera opposite: 15 Gy Folie Sauerwein PTCOG 53 Shanghai 2014
21 Dose distribution of a bi-nuclide plaque tumor: 8 mm dose: apex: 100 Gy base 1200 Gy sclera opposite: 9 Gy Folie Sauerwein PTCOG 53 Shanghai 2014
22 I-125 / Ru-106 bi-nuclide-plaque Advantages as compared to a 125 I-plaque > contact dose < integral dose > dose to the tumor < dose to structures at risk For tumors with height 7 11 mm Folie Sauerwein PTCOG 53 Shanghai 2014
23 Modified peneasy/penelope simulation CCB plaque, 7.5 mm apical height tumour Strahlenther Onkol (2013) 189, Folie Sauerwein PTCOG 53 Shanghai 2014
24 Modified peneasy/penelope simulation Cumulative dose-volume histograms Folie Sauerwein PTCOG 53 Shanghai 2014 Strahlenther Onkol (2013) 189, 68-73
25 Surgical technique Additional mattress suture Correlation of ophthalmoscopy and transillumination Folie Sauerwein PTCOG 53 Shanghai 2014
26 Follow up after Ru-106 brachytherapy juxta-papillary melanoma 8 mois 33 mois Folie Sauerwein PTCOG 53 Shanghai 2014
27 Local recurrences after Ru-106 P<0.001 N=1069 Tumor thickness < 4 mm 4-7 mm > 7 mm mois Folie Sauerwein PTCOG 53 Shanghai 2014
28 Visual acuity after after Ru-106 vision N=898 Blindness = CF and less N = 2536 juxtapapillary midperiphery periphery/cb months Folie Sauerwein PTCOG 53 Shanghai 2014 months
29 Visual acuity after I-125 Shields et al Folie Sauerwein PTCOG 53 Shanghai 2014
30 Ru-106: limits scleral necrosis incomplete destruction Tumor height Folie Sauerwein PTCOG 53 Shanghai 2014
31 I-125: limits Complications Long standing exsudative retinal detachment Radiation cataract Radiation induced optic neuropathy Radiation retinopathy, ocular ischemia, neovascular glaucoma Folie Sauerwein PTCOG 53 Shanghai 2014
32 I-125: limits Folie Sauerwein PTCOG 53 Shanghai 2014
33 I-125/Ru-106 bi-nuclide-plaque results N=100; mean follow-up 30 months Secondary enucleation in 15 eyes, 2 because of recurrent tumor growth Complications: Cataract 66% Retinopathy 47% Radiation papillopathy 44% Scleral staphyloma 15% Secondary glaucoma 11% Folie Sauerwein PTCOG 53 Shanghai 2014
34 Retinoblastoma brachytherapy 106 Ru vs. 125 I Essen (2005) Shields et al (2001) Treatment period Treated tumors 175 ( 106 Ru) 178 ( 125 I) Mean age [months] 23 ( ) 12 (1 96) Tumour diameter [mm] 7.5 ( ) 7.7 ( 1-18) Tumour height [mm 3.7 ( 1-7.6) 4.1 ( ) Distance to optic disk [mm] 7.2 ( 0 21) 6.4 ( 0 17) Retinal detachment 22 / / 178 Vitreous seeding 37 / / 178 Primary brachytherapy 56 / / 178 Mean duration of radiation 69 h 68 h Mean dose apex / base (rounded) 138 Gy / 419 Gy (NIST) 42 Gy /155 Gy Tumour recurrence / mean interval 4.6 % / 12.9 Monate 17% / 8 Monate Radiation retinopathy 12 % 26 % Folie Sauerwein PTCOG 53 Shanghai 2014
35 Proton treatment of ocular tumors Folie Sauerwein PTCOG 53 Shanghai 2014
36 % of dose Depth dose distribution 100 protons Cobalt photons 25 MV 50 electrons Depth (cm) Sauerwein Folie PTCOG 53 Shanghai 2014
37 % of dose Depth dose distribution Dose distribution in the Bragg peak: not convenient to treat a tumor. The peak needs to be enlarged, (or spread-out, or modulated) Folie Sauerwein PTCOG 53 Shanghai 2014
38 % of dose Depth dose distribution Dose distribution in the spread-out Bragg peak: 90 now suitable to treat a tumor with safety margins Folie Sauerwein PTCOG 53 Shanghai 2014
39 Wedge filter The dose distribution can be optimized by a wedge filter sparing the macula while maintaining a sufficient safety margin Folie Sauerwein PTCOG 53 Shanghai 2014
40 Bolus eyelid assumed at "-x" mm "0" mm deformation of isodoses by eyelid profile proton beam excessive irradiation due to eyelid at "-x" mm eyelid profile eye optic nerve Folie Sauerwein PTCOG 53 Shanghai 2014
41 Bolus eyelid assumed at x" mm eyelid profile proton beam no deformation of the isodoses bolus eye optic nerve Folie Sauerwein PTCOG 53 Shanghai 2014
42 3D Conformation of the proton beam diode wedge-filter Y bolus X modulator Z Folie Sauerwein PTCOG 53 Shanghai 2014 collimator
43 dose distributions Dose distribution of a 106 Ru plaque For a tumor of 8 mm Dose distribution of a 125 I plaque 60 Gy 30 Gy 12 Gy Dose distribution of a proton beam Folie Sauerwein PTCOG 53 Shanghai Gy 30 Gy 12 Gy
44 Folie Sauerwein PTCOG 53 Shanghai 2014
45 Preparation of the patient: positioning of markers CT scan after clipping always included Folie Sauerwein PTCOG 53 Shanghai 2014
46 Positioning devices for the patient Folie Sauerwein PTCOG 53 Shanghai 2014
47 BANC OPTIQUE 190 cm collimator tube RX dégradeur modulateur faisceau dans l'air chambres plates simulation lumineuse croisillon chaise de traitement cm feuille de kapton 0.13mm faisceau sous vide collimateur Ø 50mm collimateurs Ø 5mm capteur d image diode tube RX Béton baryté 1.8m 210 cm Folie Sauerwein PTCOG 53 Shanghai cm
48 treatment DIODE DIODE WEDGE FILTERS WEDGE FILTERS BOLUS VIDEO CAMERA COLLIMATOR Folie Sauerwein PTCOG 53 Shanghai 2014
49 Challenge for treatment planning: Does the model represent the reality? All the calculations made on a relatively simple mathematical model of the eye. + + The anatomy may differ from the model. To be accurate, the validity of the model has to be checked by CT and the model to be modified if necessary. Folie Sauerwein PTCOG 53 Shanghai 2014 CT-scan
50 If the model is not accurate, you will not hit the target Underdosage of real tumor Wrong model Folie Sauerwein PTCOG 53 Shanghai 2014
51 Positioning: same tumor, 3 different positions I II III Folie Sauerwein PTCOG 53 Shanghai 2014
52 Dose distributions for the three different positions lateral view 20% 50% 90% Folie Sauerwein PTCOG 53 Shanghai 2014 wide angle fundus view
53 20% 50% 90% Folie Sauerwein PTCOG 53 Shanghai 2014
54 Outcome of Uveal Melanoma treated in Nice (n= 2500) Percent Overall survival All Patients < 14.6 mm f > 14.6 mm f P = Local control 67% Months 82% 73.8% 98% T1 & T2 84% T3 & T4 P = Disease free survival < 5 mm thick > 5 mm thick P < Months Enucleation-free survival T1 & T2 T3 & T4 P = % 66 % 0 Folie Sauerwein PTCOG 53 Shanghai Months Months
55 Intraocular tumors: indications for different treatment modalities Type of applicator/ irradiation 106 Ru applicator mixed 106 Ru/ 125 I 125 I protons Maximal tumor thickness allowing an adequate dose distribution 5-7mm (depending from applicator) 6-10 mm (important influence of the activity) mm (depending from applicator) Homogeneous dose distribution always possible Depth dose distribution behind the target volume (% of dose at the apex) 1 mm: ca. 60% 5 mm: ca. 10% ca. 75 % ca. 10 % ca % ca % ca. 50% 0 Dose in healthy tissues prior the target volume (% of dose at the apex) ca 30-60% Lateral dose distribution 1 mm: ca. 20% ca % ca % (% of dose at the apex) 5 mm: ca. 3% ca % ca. 5-25% ca. 50% 0 Folie Sauerwein PTCOG 53 Shanghai 2014
56 Tumors of the conjunctiva: orphan diseases non-hodgkin lymphoma malignant melanoma squamous cell carcinoma extremely rare lesions: adeno-squamous carcinoma rhabdomyosarcoma others Folie Sauerwein PTCOG 53 Shanghai 2014
57 Complex target volume Complex geometry The problem of the fornix The problem of the depth Organs at risks in the neighborhood Target volume is also organ at risk Folie Sauerwein PTCOG 53 Shanghai 2014
58 Dose? No systematic dose finding studies Different tumor entities need different doses Due to the geometry there is always a dose gradient in the target volume to be considered Folie Sauerwein PTCOG 53 Shanghai 2014
59 Why protons? ballistic precision of the proton beam homogeneous irradiation of a complex treatment volume (necessity to treat large volume of bulbar and tarsal conjunctiva while sparing the internal structures in the eye) steep dose gradients at the edges and depth: protection of healthy structures Folie Sauerwein PTCOG 53 Shanghai 2014
60 Proton irradiation of conjunctival tumors distal shape of the irradiated volume: reproduces the relief of the beam entrance 20% Proton beam Clip Folie Sauerwein PTCOG 53 Shanghai 2014
61 Treatment technique Protection of intraocular structures Bolus: (gel+plexiglas-slice) 20% Proton beam Plane beam entrance: distal shape of the irradiated volume is flat Clip Folie Sauerwein PTCOG 53 Shanghai 2014
62 Treatment technique Bolus Folie Sauerwein PTCOG 53 Shanghai 2014
63 Treatment technique Semi-hemispherical plexiglas-compensator reduces the proton energy and modulates their range to protect healthy structures Folie Sauerwein PTCOG 53 Shanghai 2014 shielded volumen
64 Treatment technique Individual plexiglas-compensator bolus 20% Proton beam Clip Irradiated volume Folie Sauerwein PTCOG 53 Shanghai 2014 Protected volume
65 Dose distribution Folie Sauerwein PTCOG 53 Shanghai 2014
66 Treatment technique Individual plexiglas-compensator bolus Central shielding 20% Proton beam Clip Irradiated volume Folie Sauerwein PTCOG 53 Shanghai 2014
67 Individual collimators and compensators Double boost Partial protection of cornea and limbus Boost Folie Sauerwein PTCOG 53 Shanghai 2014 Extension /internal canthus
68 Folie Sauerwein PTCOG 53 Shanghai 2014
69 Dose prescription Large field irradiation 6 fractions of 5.2 Gy (6Gy Co Eq) Folie Sauerwein PTCOG 53 Shanghai 2014 Small field irradiation 2 fractions of 6.9 Gy (8Gy Co Eq)
70 Recurrences after proton radiotherapy (N = 20) - 6/20 (30%), 22.1 ± 5.7 months after therapy 3/6 within the target volume (31 Gy) 1/6 within the boost volume (45 Gy) 2/6 outside the target volume Exenteration 2/20 (10%) Metastatatic disease 6/20 (39%) Tumor-related death 4/20 (20%) Folie Sauerwein PTCOG 53 Shanghai 2014
71 survival Conjunctival Melanomas Survival Survival at median follow-up 30 months: 80.0% % of survival Folie Sauerwein PTCOG 53 Shanghai 2014 Months
72 The future of proton therapy for eye tumors? Pulsed beam Pencil beam scanning Image based treatment planning MeV Dedicated machine 65 MeV EYEPlan Folie Sauerwein PTCOG 53 Shanghai 2014
73 High energy beams and PBS for small, superficial tumors Collaboration Folie Sauerwein PTCOG 53 Shanghai 2014 work in progress Poster 005
74 Cyclotrons with continuous beams Folie Sauerwein PTCOG 53 Shanghai 2014
75 Synchrotron with pulsed beam w/o RiFi w RiFi DDF 80/20 (mm) DDF 90/10 (mm) Courtesy: Mario Ciocca Folie Sauerwein PTCOG 53 Shanghai 2014
76 PBS for ocular tumors? Spot size: 2 mm MC- simulation Courtesy: Jerome Mandrillon Folie Sauerwein PTCOG 53 Shanghai 2014
77 Bilateral retinoblastoma very young children multiple tumors in both eyes hereditary high risk of secondary cancer Folie Sauerwein PTCOG 53 Shanghai 2014
78 Secondary malignancies after RT in retinoblastoma Sethi et al. Cancer 2014 Folie Sauerwein PTCOG 53 Shanghai 2014
79 Dose distribution 6MeV Photons Folie Sauerwein PTCOG 53 Shanghai 2014
80 Retinoblastomkollimator (mit/ohne Zusatzkollimator) Phys. Med. Biol (2012) 57, Medical Physics (2014) 41 Folie Sauerwein PTCOG 53 Shanghai 2014
81 Dose distribution protons vs. photons What is better??? Folie Sauerwein PTCOG 53 Shanghai 2014
82 Protons can do better! Folie Sauerwein PTCOG 53 Shanghai 2014
83 RADIOTHERAPY OF THE ORBIT IN CHILDREN Folie Sauerwein PTCOG 53 Shanghai 2014
84 Irradiation of the orbit in children Folie Sauerwein PTCOG 53 Shanghai 2014
85 6 years after proton therapy of the orbit retinoblastoma tumor cells in the orbit 3 y old boy follow up 6 years Folie Sauerwein PTCOG 53 Shanghai 2014
86 6 years after brachytherapy of the orbit retinoblastoma tumor cells in the orbit 6 months old boy follow up 6 years Folie Sauerwein PTCOG 53 Shanghai 2014
87 Low dose rate brachytherapy of the orbit Strahlenther Onkol (2011) Folie Sauerwein PTCOG 53 Shanghai 2014
88 Radiotherapy of the orbit Folie Sauerwein PTCOG 53 Shanghai 2014
89 Radiotherapy of the orbit Folie Sauerwein PTCOG 53 Shanghai 2014
90 summary The dose distribution of protons is different from the dose distribution of photons not necessarily better If this difference is used in an appropriate way, it may lead to a benefit for the patient In any case: protons are wonderful Folie Sauerwein PTCOG 53 Shanghai 2014
91 Joël Herault Pierre Chauvel Dirk Flühs Norbert Bornfeld Lorenzo Brualla Gaëlle Angellier Henrike Westekemper Clare Stannard Jerome Mandrillon Mario Ciocca
92 Thank you! Folie Sauerwein PTCOG 53 Shanghai 2014
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