Radiobiology of Eye Plaque Brachytherapy

Here are a few pertinent publications:

Biologically Effective Dose (BED) is a measure of the true radiobiological effect delivered by a particular combination of radiation dose per fraction and total dose to a particular tissue. The formula is characterized by a specific α/β ratio, where α is the cell kill per Gy of the initial linear component (on a log-linear plot) and β the cell kill per Gy2 of the quadratic component of the radiation survival curve.

A very wide range of LQ model α/β ratios have been reported for uveal melanomas by Aardweg et. al. (Table 1) , which appear to differ considerably from cutaneous melanomas, so a fairly conventional α/β ratio of about 10 for acute effects and 3 for late effects was assumed for the calculations that follow.

Table 1 from Gerard J. M. J. van den Aardweg, Emine Kilic, Annelies de Klein, and Gregorius P. M. Luyten, Dose Fractionation Effects in Primary and Metastatic Human Uveal Melanoma Cell Lines, Investigative Ophthalmology & Visual Science, November 2003, Vol. 44, No. 11.

Table1


Below is a comparison of BED, calculated using a version of the linear-quadratic (LQ) model (Fowler 1989) for Low Dose Rate (LDR) brachytherapy, for typical eye plaque implant regimens of 85 Gy total dose delivered over a period of 3 to 8 days. The calculation was performed using the Eye Physics companion shareware product TDFPlan with the course modality set to LDR, assuming a T-half for repair of 1.5 hours and a Relative Biological Effect (RBE) of 1.4 for I-125 radiation.


TDFPlanComparison

In the Integrated Multicourse Regimen (IMR) section of the TDFPlan window capture shown above we see that the BED for acute effects (the A BEDn column) ranges from about 161 Gy10 for a 3 day implant down to about 135 Gy10 for an 8 day implant. The acute effects BEDn of 137.38 Gy10 for a 7 day (168 hr) implant is highlighted. The BED for late effects ranges from about 259 Gy3 down to about 173 Gy3. For the same total dose (e.g. 85 Gy), shorter duration implants deliver a greater biological effect to both the tumor and late responding normal tissues.

In the clinic, the concept of a therapeutic ratio (e.g. TCS42 pg.41) may be defined as the percentage of tumor cures that are obtained for a given level of normal tissue complications. According to Fowler the ratio of the tumor (ie acute effects) BED to the late BED is a good therapeutic ratio. Decreasing the dose rate by delivering the same total dose (e.g. 85 Gy) over a longer time period increases the therapeutic ratio (as does lowering the dose per fraction in external beam radiotherapy).

Days Acute BED Gy10 Late BED Gy3 Therapeutic Ratio
3 161.13 259.45 0.62
4 150.85 225.15 0.67
5 144.59 204.31 0.71
6 140.39 190.31 0.74
7 137.38 180.26 0.76
8 135.11 172.69 0.78

From a logistical perspective, Eye Physics recommends an implant duration of about 1 week because it fits well with most physician's and operating room schedules and may have, at least in theory, a therapeutic radiobiological advantage compared to shorter duration implants, especially if the α/β ratio of ocular melanoma is indeed greater than that of late responding tissues.

Because many institutions use different implant durations, it may be worth investigating the utility of adjusting one's total dose prescription to match the biological effect of some as yet unspecified, standardized treatment regimen.

TherapeuticRatio