Author: Mishra K.K.; Daftari I.; Scholey J.; Quivey J.; Kacperek A.; Afshar A.R.; Damato B.; Char D.
Abstract: Purpose : Proton beam treatment for uveal melanoma (UM) has been well established internationally with dedicated ocular beamlines. With the emergence of universal, high-energy, non-fixed beamlines, we share key practices to minimize side effects. Methods : The University of California, San Francisco (UCSF), USA, and the Clatterbridge Cancer Centre (CCC), UK, both have longstanding facilities with dedicated, fixed, low-energy, ocular lines, which produce 67.5 and 60.0 MeV proton beams, respectively (range up to 3 cm). In total 5927 ocular patients, 93% with UM, have been treated. Standard UM dose is 56 Gray Equivalent (GyE) at UCSF and 57.2 GyE at CCC, delivered in 4 fractions. Planning and delivery procedures were analyzed as a bi-institutional effort to communicate key concepts to developing centers. Results : Low-energy dedicated eye beamlines provide critical beam characteristics for normal eye tissue sparing. 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). Analyses confirm that planned doses to critical ocular structures are independent predictors of vision, neovascular glaucoma, and other clinical outcomes (e.g. 28 GyE to macula [P<.0001], optic nerve [P<0.0004], lens [P<.0001], and ciliary body [P<.0001]). A rational 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. A common dosing regimen for UM is 60 GyE in 4 fractions globally. Unrandomized early retrospective data showed 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 systematically evaluated to minimize side effects. Eyelid toxicity is minimized by retraction techniques or treatment through closed lids. Conclusions : Experienced proton centers at UCSF and CCC with dedicated, low-energy, fixed eyelines, provide important practical clinical concepts for consideration by new centers to optimize high-energy universal beamline designs, particularly to reduce normal tissue toxicity.
Abstract: Purpose : Proton beam treatment for uveal melanoma (UM) has been well established internationally with dedicated ocular beamlines. With the emergence of universal, high-energy, non-fixed beamlines, we share key practices to minimize side effects. Methods : The University of California, San Francisco (UCSF), USA, and the Clatterbridge Cancer Centre (CCC), UK, both have longstanding facilities with dedicated, fixed, low-energy, ocular lines, which produce 67.5 and 60.0 MeV proton beams, respectively (range up to 3 cm). In total 5927 ocular patients, 93% with UM, have been treated. Standard UM dose is 56 Gray Equivalent (GyE) at UCSF and 57.2 GyE at CCC, delivered in 4 fractions. Planning and delivery procedures were analyzed as a bi-institutional effort to communicate key concepts to developing centers. Results : Low-energy dedicated eye beamlines provide critical beam characteristics for normal eye tissue sparing. 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). Analyses confirm that planned doses to critical ocular structures are independent predictors of vision, neovascular glaucoma, and other clinical outcomes (e.g. 28 GyE to macula [P<.0001], optic nerve [P<0.0004], lens [P<.0001], and ciliary body [P<.0001]). A rational 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. A common dosing regimen for UM is 60 GyE in 4 fractions globally. Unrandomized early retrospective data showed 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 systematically evaluated to minimize side effects. Eyelid toxicity is minimized by retraction techniques or treatment through closed lids. Conclusions : Experienced proton centers at UCSF and CCC with dedicated, low-energy, fixed eyelines, provide important practical clinical concepts for consideration by new centers to optimize high-energy universal beamline designs, particularly to reduce normal tissue toxicity.
