Proton Radiation Therapy of Ocular Melanoma at PSI

Size: px

Start display at page:

Download "Proton Radiation Therapy of Ocular Melanoma at PSI"

Ross Morton
5 years ago
Views:

1 Proton Radiation Therapy of Ocular Melanoma at PSI G. Goitein*, A. Schalenbourg, J. Verwey*, A. Bolsi*, C. Ares*, L. Chamot, E. Hug*, L. Zografos *Paul Scherrer Institut, 5232 Villigen PSI; Hôpital Ophtalmique, Av. de France 15, 1004 Lausanne

Ocular Melanoma Rare tumors, ~ 40 50 cases/year in CH Melanomas develop from melanocytes Ocular melanomas rise in the pigmented parts of the eye: choroida, ciliary body, iris.

2 Ocular Melanoma Rare tumors, ~ cases/year in CH Melanomas develop from melanocytes Ocular melanomas rise in the pigmented parts of the eye: choroida, ciliary body, iris. In addition, melanomas occur in the conjunctiva and the eye lid The precise cause of the development of ocular melanoma is unclear (as for many other tumors) Origin of ancestors, genetique (race), endogenic/hormonal, UV during childhood, are being discussed

Ocular Melanomas Are malignant with metastatic potential Diagnose is mostly made by clinical examination; patients complain about impaired vision, light flashes, impression of

3 Ocular Melanomas Are malignant with metastatic potential Diagnose is mostly made by clinical examination; patients complain about impaired vision, light flashes, impression of catarrhact Funduscopy allows diagnosis in most cases Additional examinations such as US, fundus photography, fluorescein-angiography, CT, MRI and, if necessary, biopsy are performed

4 Ocular Melanoma Until the 1970 s enucleation was the therapy of choice Irradiation with radioactoive plaques is efficient if the hight of the lesion does not lead to underdosage in the apex of the tumor Protons have shown to be most efficient in the treatment of this particular, rare, and demanding disease Ocular melanomas are the by far largest tumor entity treated with proton beams worldwide: > patients

5 Proton radiation therapy for ocular tumors was introduced at PSI (former SIN) in 1984 The technology of the first therapy installation at the HCL was copied with modifications The therapy planning program EyePlan was and still is in use; modifications and extensions have been made and introduced into the daily routine in collaboration with the Clatterbridge Center for Oncology CCO All ophthalmological patients are referred and surgically prepared by the University Eye Hospital Hôpital Ophtalmique Jules Gonin in Lausanne Follow-up examinations are performed by the external ophthalmologists and by HOJG

6 The Paul Scherrer Institut Center for Proton Therapy GG 11/09

7 Proton therapy for ocular melanoma Diagnose

8 Proton therapy for ocular melanoma Surgery to suture tantalum clips around the tumor base Tumor Tantal clip Optic nerve Surgical procedure (under general anaesthesia): luxation of the eye, translumination to make the tumor base visible, suturing of the clips as close as possible to the tumor base

9 Proton therapy for ocular melanoma Simulation Lid retractor Fixation light to keep the ganzing angle Bite block and face mask to immobilize the head Position in front of the beam tube

Proton therapy for ocular melanoma Radiological

information about the clip position in ralation

10 Proton therapy for ocular melanoma Radiological measuring of the clip position vis-à-vis the central beam axis Plastic model of an eye bulb with tantalum clips Surgical report with information about the clip position in ralation to the tumor base Clip positions as seen in the X-ray image

Proton therapy for ocular melanoma Individual treatment plan Eyeplan: The first computer based therapy planning program: the eye is modelled, first as a shere,

11 Proton therapy for ocular melanoma Individual treatment plan Eyeplan: The first computer based therapy planning program: the eye is modelled, first as a shere, meanwhile also as elypsoid. Clip positions in relation to the reconstructed tumor base are included, the optimal gazing angle is defined and the dose distribution is calculated.

12 Proton therapy for ocular melanoma Individual collimators

13 Patient numbers March 1984 December 2009 Total of > n year

14 A great moment for HHJG, PSI and all involved people August patients The Team 2009 GG 03/09

15 Patient numbers March 1984 December 2008 Total of 5076 Of the 5076 patients treated 85% had uvueal melanomas 2.5% conjunctival melanomas ~1% iris melanomas relaps of chor. mel. choroidal melanoma conjunctival tumors chor. hemangiomas intraocular M1 ARMD iris melanomas vasc. retinal tu's miscell. Tumor type 2.6% relapses of choroidal melanomas 4.1% choroidal hemangiomas 2.5% conjunctival tumors 1.3% intraocular metastases 1.2% ARMD (Age Related Macular Degeneration) 0.7% iris melanomas 0.4% vascular retinal tumors 0,2% miscellaneous

16 Proton therapy for ocular melanoma Previous analysis of 2837 patients treated between has shown that Local recurrence has influence on survival (Tumor Related Death). TRD from ocular melanoma is death from distant metastases Therefore, local tumor control is the primary goal of proton radiotherapy for ocular melanoma % TRD at 10 ys no rec. 0-2 ys >2 ys % TRD Time after PT

17 2993 Patients analyzed (2006), who received proton radiation therapy between III/1984 and VIII/2005 Follow up 15 months 21 years; median 3ms Confirmed diagnosis of melanoma (HOJG Lausanne) Unilateral disease No reduced (<2mm) safety margin Negative familial history Visible fundus No adjuvant chemotherapy Proton dose of 4x15= 60 Gy RBE (former CGE, Cobalt Gray Equivalent)

18 Patient characteristics Age min max Mean / median <20 / / / > /57 22/ 1307 / % / 43.9% / 48.6% / 6.8% Gender male / female 1433 / % / 52.1% Lagest tumor diameter (mm) Tumor thickness (mm) Position of anterior tumor margin Distance of posterior tumor margin to optic disc (mm) Distance of posterior tumor margin to macula (mm) min / max mean / median 10 / / / >20 min / max mean / median 3 / / / >10 anterior to equator ciliary body iris min / max mean / median invasion of / contact with optic disc <2 / >2 min / max mean / median invasion of / contact with macula <2 / >2 4 / / / 1051 / 1208 / % / 35.1% / 40.4% / 16.4% 0.9 / / / 827 / 1369 / % / 27.6% / 45.7% / 11-5% / / / / / / / / % 30.1% 4.0% 6.2% / 11.8% 17.9% / 64.1% 15.0% / 9.3% 18.9% / 56.8%

19 Patient characteristics Exteriorisation (extra-scleral tumor extens.) absent present % 4.7% Symptoms absent present % 89.6% Diagnose fortuitous through symptoms % 87.2% Visual acuity (%) 0.8 / / / / 577 / 610 / % / 19.3% / 20.4% / 18.9% Retinal detachment (quadrants) <1 q/ 1qs / 2 qs / 3 qs / total 1774 / 586 / 566 / 64 / % / 19.6% / 18.9% / 2.1% / 0.1% Haemorrhage absent / tumor / mild vitreous / massive vitreous 2663 / 221 / 83 / 11 89% / 7.4% / 2.8% / 0.4% Melanocytosis absent present % 3.0%

20 Factors influencing outcome Survival (lr- p-value) Survival (Cox regr. an.p) Local control (lr- p-value) Local control (Cox regr. an.p) Age 55> < n.s. Gender n.s Localization anterior to aequ. iris ciliary body < < <0.001 < <0.001 Largest tumor diameter < Tumor thickness < (>10mm) Exteriorization < Retinal detachment <0.001 n.s

21 Local relapse Largest tumor diameter lr-p-value <10mm (10/244) 10-15mm (20/1051) mm (31/1208) time Freedom from LF 96% 95% 95% 98% 98% 95% 97% 96% 93% > 20mm (22/490) 94% 92% 92%

22 <10mm - 5/10/15 ys mm - 96/93/89% mm - 90/81/77% >20mm - 77/59/46%

23 Local relapse Tumor thickness lr-p-value mm (11/454) 3.1-5mm (14/827) mm (43/1369) time Freedom from LF 98% 98% 98% 97% 97% 97% 96% 95% 91% > 10mm (15/343) 94% 93% 87%

24 <3mm - 5/10/ 3.1-5mm - 95/90/86% mm - 89/79/75% >10mm - 80/68/59%

25 Local relapse zs NO local relapse 91/84/80%

Enucleation Tumor thickness lr-p-value 0.001 time enucleation 3mm (9/454) 2% 4% 4% 3.

26 Enucleation Tumor thickness lr-p-value time enucleation 3mm (9/454) 2% 4% 4% 3.1-5mm (25/827) 3% 5% 5% mm (121/1369) 10% 14% 19% > 10mm (60/343) 23% 26% 39%

27 Enucleation Tumor diameter time enucleation 3mm (8/244) 3.1-5mm (54/1051) lr-p-value mm (100/1208) lr-p-value >10mm (53/490) Lr-p-value < % 4% 4% 6% 7% 11% 9% 13% 18% 15% 18% 18%

28 Enucleation Distance post. tu-margin to optic disc lr-p-value <0.001 Invasion of disc (17/187) Contact (46/352) lr-p-value > 0-2mm (32/536) lr-p-value >2mm (120/1918) lr-p-value <0.001 time enucleation 11% 14% 27% 14% 19% 19% 7% 9% 13% 7% 9% 13%

29 Clinical causes for enucleation Glaucoma Loss of function Confirmed local relapse Severe inflammation Suspicion of local relapse Painful eye Unclear tumor situation Phtisis bulbi

30 Visual acuity after proton radiation therapy Reduced visual acuity prior to proton therapy (most patients see the ophthtalmologist because of reduced vision!) Tumor thickness Small distance between tumor and optic disc & macula Amount of retinal detachment Advanced age Part of previous anaysis

31 Conclusion Proton radiotherapy for ocular melanoma results in very satisfying local control (overall and tumor specific survival rates (overall ys) Differentiated outcome analyses show that age tumor size (diameter and thickness) localization and relation to other structures (optic disc, ciliary body, iris) have the strongest influence on local failure, enucleation rate and survival

32 2 - the future of ocular proton radiotherapy at PSI COMET the new dedicated medical proton accelerator PIF experim. beam line 2 Gantry 2 (2007) Existing Gantry 1

25 Years of Proton Radiation Therapy at PSI an Overview

25 Years of Proton Radiation Therapy at PSI an Overview Gudrun Goitein for the Team of the Center for Proton Therapy Center for Proton Therapy Paul Scherrer Institut (www.psi.ch) 5232 Villigen PSI Switzerland