Comparison of integrated biological effectiveness of eye plaques with ¹²⁵I and ¹⁰³Pd photon sources using equivalent...

The COMS (Collaborative Ocular Melanoma Study) eye plaques are based on the application of low-energy photon sources such as iodine-125 (¹²⁵I) and palladium-103 (¹⁰³Pd). Compared to ¹²⁵I, ¹⁰³Pd 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.

The goal of this article is to show that the higher RBE of lower-energy photons from ¹⁰³Pd 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 ¹²⁵I sources.

Biological effectiveness of COMS eye plaques with ¹²⁵I and ¹⁰³Pd 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.

In the simulations with a hypothetical RBE = 1, the EUD_RBE for eye plaques with both ¹²⁵I and ¹⁰³Pd 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 ¹⁰³Pd sources is lower compared to ¹²⁵I sources. If the measured RBE of 1.4 and 1.9 is applied for ¹²⁵I and ¹⁰³Pd, respectively, the EUD_RBE for eye plaques becomes larger than the reference dose of 50 Gy(RBE). The range of EUD_RBE for ¹²⁵I 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 ¹⁰³Pd is within 57-67 Gy(RBE), which is higher compared to ¹²⁵I.

The effects of RBE for COMS eye plaques with ¹²⁵I and ¹⁰³Pd sources should be considered to explain the tumor control probability (TCP) > 80% observed in clinical practice. The EUD_RBE for ¹⁰³Pd sources is larger than the EUD_RBE for both the ¹²⁵I sources and hypofractionated proton therapy; therefore, the dose de-escalation relative to 85 Gy may be considered.