Primary malignant tumors of the eye and orbit are rare. Their treatment requires special knowledge of the anatomical, conditions, individualized, usually very complex, irradiation techniques, and cooperation between the, clinical disciplines involved. The risks are blindness-related, extreme loss of quality of life, cosmetic changes, to patient appearance, and economic effects. With few, able to pay for complex radiation techniques, only select, patients, willing insurance companies, and high-resource, national health systems allow complex radiation therapy, techniques that preserve eye, function, and life., The rarity of eye tumors and the complex technical, requirements needed to develop conservative treatments, led to the formation of highly specialized regional, referral centers. Unfortunately, each center typically has, only one radiation technology for ocular malignancies., These radiation alternatives include plaque brachytherapy, (e.g., iodine-125 [125I], palladium-103 [103Pd], and/, or ruthenium-106 [106Ru]) or proton beam irradiation.1, Since there is usually only one approach available at each, center, there is little possibility of choosing the optimal, radiation technique for each clinical situation., This chapter reflects our initiative to pair two clinical, centers—one in Essen, Germany and one in Nice,, France—such that each offered a different treatment, modality to maximize clinical outcomes based on select, physical tumor characteristics. We considered the following, hypothetical treatment recommendations. For, example, in Essen we used 106Ru beta-applicators for relatively, flat tumors, as to utilize its most favorable ratio, of tumor dose/dose to normal tissues, as well as 125I (or, mixed 106Ru with 125I), whose dose distribution allows, treatment of larger target tumor volumes.2 Other nonparticipating, centers have reportedly used low-dose rate, (LDR) 90Sr and 103Pd as well as high-dose rate (HDR) 90Y, (see Chapters 17–19, 21, and 22).3-5 However, it is important, to note that along with deeper plaque radiation, penetration, existing LDR plaque therapy is associated, with a wider side-scatter penumbra, leading to less, favorable irradiation of surrounding healthy tissues.6-8 In, our experience, plaque brachytherapy for tumors at the, posterior pole (in the immediate vicinity of the radiation-, sensitive structures of the macula, optic disc, and, optic nerve) rarely results in functional vision. In contrast,, proton treatment of tumors of the posterior pole, offers at least theoretical advantages, provided that the, beam energy, treatment planning, and technical implementation, offer the highest quality to obtain precision., In our experience, compared to LDR plaque brachytherapy,, proton therapy can produce better results in large, tumor volumes where there exists more dose homogeneity., Thus, we have seen less subsequent necrosis, local, accumulation of toxic degradation products, and secondary, glaucoma. However, in general practice, the potential, of proton therapies has not yet been realized in that the, currently used high single-dose fractions have had an, opposite effect., In 1991, a collaboration between the Cancer Center, Antoine Lacassagne in Nice (France) and the University, Hospital in Essen (Germany) provided availability, to a dedicated proton facility for German patients. Cases, were selected for proton therapy when brachytherapy, was not technically feasible (Mind map 20-1). Examples, include diffuse conjunctival melanoma and intraocular, tumor locations that would certainly lead to short-term, blindness (e.g., choroidal melanomas near or touching, the optic disc and/or fovea). This chapter reports on our, subjective experience over 3 decades of proton therapy, and teaches on pragmatic aspects we have used to optimize, our proton beam therapy.