Title:
Radiobiology for eye plaque brachytherapy and evaluation of implant duration and radionuclide choice using an objective function.

Abstract:
Clinical optimization of Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy is currently limited to tumor coverage, consensus prescription dosage, and dose calculations to ocular structures. The biologically effective dose (BED) of temporary brachytherapy treatments is a function of both chosen radionuclide R and implant duration T. This study endeavored to evaluate BED delivered to the tumor volume and surrounding ocular structures as a function of plaque position P, prescription dose, R, and T.
Plaque-heterogeneity-corrected dose distributions were generated with MCNP5 for the range of currently available COMS plaques loaded with sources using three available low-energy radionuclides. These physical dose distributions were imported into the PINNACLE(3) treatment planning system using the TG-43 hybrid technique and used to generate dose volume histograms for a T = 7 day implant within a reference eye geometry including the ciliary body, cornea, eyelid, foveola, lacrimal gland, lens, optic disc, optic nerve, retina, and tumor at eight standard treatment positions. The equation of Dale and Jones was employed to create biologically effective dose volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs. Isobiologically effective prescription doses were calculated for T = 5 days down to 0.01 days, with BEDVHs subsequently generated for all ROIs using correspondingly reduced prescription doses. Objective functions were created to evaluate the BEDVHs as a function of R and T. These objective functions are mathematically accessible and sufficiently general to be applied to temporary or permanent brachytherapy implants for a variety of disease sites.
Reducing T from 7 to 0.01 days for a 10 mm plaque produced an average BED benefit of 26%, 20%, and 17% for (103)Pd, (125)I, and (131)Cs, respectively, for all P; 16 and 22 mm plaque results were more position-dependent. (103)Pd produced a 16%-35% BED benefit over (125)I, whereas (131)Cs produced a 3%-7% BED detriment, independent of P, T, and plaque size. Additionally, corresponding organ at risk physical doses were lowest using (103)Pd in all circumstances.
The results suggest that shorter implant durations may correlate with more favorable outcomes compared to 7 day implants when treating small or medium intraocular lesions. The data also indicate that implant duration may be safely reduced if the prescription physical dose is likewise diminished and that (103)Pd offers a substantial radiobiological benefit over (125)I and (131)Cs irrespective of plaque position, implant duration, and tumor size.