Author: Mishra K.K.; Daftari I.K.; Quivey J.M.; Kacperek A.; Afshar A.R.; Scholey J.; Damato B.; Char D.H.
Abstract: Purpose/Objective(s): Proton beam treatment for ocular tumors has been well established with dedicated eye beamlines internationally. Given the emergence of universal, high-energy, non-fixed beamline options, we share key practices for uveal melanoma (UM) treatment planning and delivery. We focus particularly on practical clinical and physics concepts to minimize important ocular side effects. Materials/Methods: Practices were studied from two well-established international dedicated proton ocular institutions with very longstanding facilities, both using fixed, low-energy, ocular beamlines to treat eye tumors only. Since the 1970s and 1980s until now, the respective cyclotrons produce 67.5 and 60.0 MeV proton beams (range up to 3 cm). In total 5927 ocular patients, 93% with UM, have been treated. Standard UM dose is 56 Gray Equivalent (GyE) and 57.2 GyE, respectively, delivered in 4 fractions. Planning and delivery procedures were analyzed as a bi-institutional effort to communicate key concepts to newer developing proton centers. Result(s): Normal eye tissue sparing is related to critical beam characteristics provided in the setting of low-energy dedicated eye beamlines. Both centers offer a very sharp dose fall off (distal ~1 mm and lateral ~1.1-1.6 mm), high dose homogeneity, excellent range precision and short treatment time (~0.5-2 minutes). Planned doses to critical ocular structures are independent predictors of ocular complications such as vision loss and neovascular glaucoma, including the following parameters: 28 GyE to macula [P<.0001], optic nerve [P<0.0004], lens [P<.0001], and ciliary body [P<.0001]. A systematic tumor/critical structure dose evaluation is used to optimize treatment parameters, i.e. lateral margin, distal range, gaze angle, and aperture shape. New high-energy non-dedicated beam designs, which degrade energy to deliver ocular treatment, may require significant beam adjustment and treatment planning procedures to achieve adequate characteristics. Regarding UM dose, a common regimen is 60 GyE in 4 fractions globally. Unrandomized early retrospective data shows lower local tumor control with 48 GyE (P = 0.02). Critical structures including the retina, lacrimal gland, cornea, tear ducts, lids, bony orbit, and limbal stem cells are methodically evaluated to minimize side effects. Eyelid toxicity is reduced by institutional retraction techniques or treatment through closed lids. Conclusion(s): Experienced international specialty proton ocular centers with dedicated, low-energy, fixed eyelines, provide important practical concepts for consideration by developing centers to optimize high-energy universal beamline designs for eye treatments. As new centers with different beam designs emerge globally, key clinical and treatment planning/delivery practices will need to be applied, particularly to reduce potential normal tissue toxicity for ocular patients.
