Constraints in the use of repair half times and mathematical modelling for the clinical application of HDR and PDR treatment schedules as an alternative for LDR brachytherapy.

Using theoretical models based on radiobiological principles for the design of new treatment schedules for HDR and PDR brachytherapy, it is important to realise the impact of assumptions regarding the kinetics of repair. Extrapolations based on longer repair half times in a continuous LDR reference scheme may lead to the calculation of dangerously high doses for alternative HDR and PDR treatment schedules. We used the clinical experience obtained with conventional ERT and LDR brachytherapy in head and neck cancer as a clinical guideline to check the impact of the radiobiological parameters used. Biologically equivalent dose (BED) values for the in clinical practice of LDR brachytherapy recommended dose of 65-70 Gy (prescribed at a dose rate between 30-50 cGy/h) are calculated as a function of the repair half time. These BED values are compared with the biological effect of a clinical reference dose of conventional ERT with 2 Gy/day and complete repair between the fractions. From this comparison of LDR and ERT treatment schedules, a range of values for the repair half times of acute or late responding tissues is demarcated with a reasonable fit to the clinical data. For the acute effects (or tumor control) the best fits are obtained for repair half times of about 0.5 h, while for late effects the repair half times are at least 1 h and can be as high as 3 h. Within these ranges of repair half times for acute and late effects, the outcome of "alternative' HDR or PDR treatment schedules are discussed. It is predominantly the late reacting normal tissue with the longer repair half time for which problems will be encountered and no or only marginal gain is to be expected of decreasing the dose rate per pulse in PDR brachytherapy.

Radiation therapy for subfoveal choroidal neovascular membranes in age-related macular degeneration. A pilot study.

BACKGROUND: The natural course of the visual acuity of age-related subfoveal choroidal neovascularisation (CNV) membranes is poor. Laser photocoagulation of subfoveal CNV is recommended if the patient is willing to accept a large decrease in visual acuity immediately after treatment. A large proportion of patients with subfoveal CNV do not meet the Macular Photocoagulation Study Group (MPS) guidelines for laser photocoagulation. The fact that so few patients meet these criteria makes further research into new treatment techniques warranted. Ionising radiation may prevent the proliferation of endothelial cells of newly formed subretinal capillaries and may induce obliteration of the aberrant new vessels. METHODS: In this study, the effect of radiation therapy on subfoveal CNV membranes was evaluated. Four groups of ten patients were treated with external beam radiotherapy (16-MV photons) on an area of 1 cm2 (macular region) using a lens-sparing technique and total doses of 8-24 Gy. The first group received 8 Gy in one fraction. The second, third and fourth groups received 12 Gy in 2 fractions, 18 Gy in three fractions and 24 Gy in four fractions respectively. The studied parameters included best-corrected visual acuity and membrane size and leakage on the fluorescein angiogram. We included 17 occult and 23 classic CNV membranes as defined by the MPS, with a duration of less than 5 weeks at presentation. Complete ophthalmic examination including fluorescein angiography was performed before and 3, 12 and 18 months after radiation treatment. We analysed the angiogram using a standard overprojection sheet. The results concerning the visual acuity and fluorescein angiography (FA) were compared with the extensively published, natural course data. RESULTS: The first group (including three cases of occult CNV) received 8 Gy in a single fraction. In this group only four of ten patients had stable visual acuity and stable FA appearance after 21 months follow-up. The visual acuity and FA remained stable after 13.6 months follow-up in seven of the patients in group 2 (12 Gy in two fractions, four occult CNV). The third group (18 Gy in three fractions, seven occult CNV) contained six patients with stable visual acuity, although two of them had CNV deterioration on the FA (11.1 months follow-up). In the last group (24 Gy in four fractions, three occult CNV), with a short follow-up of 5.6 months, eight patients had stable visual acuity and FA appearance. We did not note any regression of the CNV membrane on the angiogram. The visual acuity in groups 2, 3 and 4 decreased to 0.1 or worse in only three cases, three cases and one case respectively after at least 6 months follow-up. CONCLUSION: Comparison of these findings with the natural history data of subfoveal age-related CNV suggests a beneficial effect of radiation therapy with a total dose of 12 Gy or more on the progression of CNV. To date no negative side effects have been observed.