Comparison of integrated biological effectiveness of eye plaques with ¹²⁵ I and ¹⁰³ Pd photon sources using equivalent uniform RBE‐weighted dose

Background The COMS (Collaborative Ocular Melanoma Study) eye plaques are based on the application of low‐energy photon sources such as iodine‐125 ( 125 I) and palladium‐103 ( 103 Pd). Compared to 125 I, 103 Pd is characterized by different radiobiological and physical parameters, which include the half‐life, relative biological effectiveness (RBE), and average photon energy. Variation of these parameters may increase or decrease the integrated cell‐killing effect of eye plaques; therefore, quantitative evaluation of biological effects may be used to optimize the dose prescription and improve the therapeutic ratio. Purpose The goal of this article is to show that the higher RBE of lower‐energy photons from 103 Pd sources counteracts the steeper dose fall‐off in heterogeneous eye plaque geometry and the effect of radiation protraction to produce the higher cell killing effect compared to 125 I sources. Methods Biological effectiveness of COMS eye plaques with 125 I and 103 Pd sources is evaluated using the equivalent uniform RBE‐weighted dose (EUD RBE ). The EUD RBE is defined as the uniform dose distribution with RBE = 1 that produces the cell survival equal to a nonuniform dose distribution with variable RBE. The EUD RBE was proposed for comparison of cell survival in radiotherapy with a nonuniform dose and the RBE effect, and such a concept can be applied to both external beam fractionated radiotherapy and continuous irradiation in brachytherapy. The EUD RBE is computed in a 1D model of COMS eye plaques using the dose distributions in a water‐equivalent medium with heterogeneity correction from MC calculations. The EUD RBE is computed in five dose fractions using the linear quadratic (LQ) cell survival model corrected for the effects of protracted irradiation and RBE. The EUD RBE for eye plaques is compared to the reference dose of 50 Gy(RBE) that is the lowest total dose (delivered in five fractions) used in hypofractionated proton therapy for ocular melanoma. Results In the simulations with a hypothetical RBE = 1, the EUD RBE for eye plaques with both 125 I and 103 Pd sources is lower than the reference dose of 50 Gy(RBE) for most of the simulated implant durations and tumor heights. Also, the EUD RBE for eye plaques with 103 Pd sources is lower compared to 125 I sources. If the measured RBE of 1.4 and 1.9 is applied for 125 I and 103 Pd, respectively, the EUD RBE for eye plaques becomes larger than the reference dose of 50 Gy(RBE). The range of EUD RBE for 125 I is within 50–60 Gy(RBE) depending on the implant duration and tumor height; therefore, the lowest EUD RBE is comparable to the dose used in hypofractionated proton therapy. The range of EUD RBE for 103 Pd is within 57–67 Gy(RBE), which is higher compared to 125 I. Conclusions The effects of RBE for COMS eye plaques with 125 I and 103 Pd sources should be considered to explain the tumor control probability (TCP) > 80% observed in clinical practice. The EUD RBE for 103 Pd sources is larger than the EUD RBE for both the 125 I sources and hypofractionated proton therapy; therefore, the dose de‐escalation relative to 85 Gy may be considered.