We also concurred that many radionuclide sources can be used, but only 125I, 103Pd, and 106Ru are used in three or more ABS-OOTF centers. Although there exist tumor thickness restrictions for 106Ru and 90Sr, 17-AAG concentration taller tumors can be treated with 125I or 103Pd techniques [7], [11], [13] and [72]. Overall, the ABS-OOTF expanded general indications for uveal melanoma patient selection (Table 2). Fianlly, we found that plaque brachytherapy is not commonly used for Rb. However, indications include: small anterior tumors in unilateral cases, for salvage after chemoreduction with subsequent alternative therapies and in select cases in which macular laser will likely cause loss of vision. The ABS-OOTF recommends

that the eye cancer community use universal

AJCC–UICC staging to define tumor size, location, and associated variables Navitoclax price [87] and [88]. This would enable multicenter communication, comparative analysis, and patient education. This in turn, would allow for collection of numbers large enough to reach statistical significance. The ABS-OOTF recommends the development of a site-specific staging system for complications after ophthalmic radiation therapy. This would facilitate scientific comparisons between treatments, help predict ophthalmic side effects, and improve informed consent. However, the ABS-OOTF acknowledges the myriad unanswered questions that challenge ophthalmic plaque brachytherapy researchers. Select questions offered by the ABS-OOTF include: What are the radiobiological differences between continuous low-dose-rate plaque brachytherapy in comparison with fractionated high-dose-rate proton beam irradiation? What is the “correct” apical prescription dose and dose rate required for treatment of uveal melanoma, and how do we accommodate for the steep

dose gradient within the tumor? For example, should there be a dose deescalation study or a thickness-based sliding scale in treatment of uveal melanoma? Can there be international standards for dosimetry to determine the relative efficacy of photons, electrons, and protons? Is there a role for radiation sensitizers during plaque therapy? Should the presence of intravitreal melanoma acetylcholine seeds affect case selection? What is the role and best timing for the use of anti-VEGF agents in treatment of radiation maculopathy and optic neuropathy? Are there differences in the efficacy of anti-VEGF agents related to radionuclide, radiation dose, and dose rate? Do notched and slotted plaques address geographic miss in the treatment of juxtapapillary and circumpapillary tumors? With regard to Rb, are there oncogenic risks of plaque brachytherapy? What are the optimal parameters for tumor size selection and radiation dose (if used before or after chemotherapy)? The ABS-OOTF hopes future research will answer some of these questions. Currently, plaque brachytherapy offers an eye and vision sparing alternative to enucleation annually for thousands of patients’ worldwide.