Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma

Background and purpose: To evaluate prospectively local tumor control and m orbidity after 1-3 fractions of stereotactic external beam irradiation (SEB I) in patients with uveal melanoma; unsuitable for ruthenium-106 brachyther apy or local resection. Material and methods: This phase I/II study includes 62 selected patients w ith uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With th e Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equa l fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated wit h three fractions of 15 GL each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean t otal 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-effect s were analyzed with the Cox proportional hazards model for possible risk f actors. 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% afte r 12, 24 and 36 months, respectively. Seven patients developed metastases ( 11%). Secondary enucleation was performed in eight eyes (13%). Morbidity wa s 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 exud ative retinal detachment. In this model, the high-dose volume irradiated wi th more than 10 Gy/fraction was the strongest risk factor for radiation-ind uced 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 ac hieving local tumor control in uveal melanoma. Further clinical studies usi ng smaller fraction doses, and consequent smaller high dose volumes, are ju stified to optimize dose and fractionation. Fractionated stereotactic irrad iation has a challenging potential as an eye preserving treatment in uveal melanoma. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.