Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.
OBJECTIVE
To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection.


METHODS
This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors.


RESULTS
Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis.


CONCLUSIONS
Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.
Zehetmayer
M
M
Department of Ophthalmology, Oncology Service, University of Vienna, Medical School, Allgemeines Krankenhaus, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Kitz
K
K
Menapace
R
R
Ertl
A
A
Heinzl
H
H
Ruhswurm
I
I
Georgopoulos
M
M
Dieckmann
K
K
Pötter
R
R
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000601:surgery*; D008875:Middle Aged; D011446:Prospective Studies; D016634:Radiosurgery / Q000009:adverse effects; D012307:Risk Factors; D014604:Uveal Neoplasms / Q000601:surgery*