PURPOSE: To investigate the effects of split-dose irradiation on primary
and metastatic uveal melanoma cell lines, with a clonogenic survival
assay. METHODS: Appropriate cell concentrations of four primary and four
metastatic human uveal melanoma cell lines were cultured for irradiation
with single doses and with two equal fractions separated by 5 hours. After
irradiation, colony formation was allowed for 7 to 21 days. Two cutaneous
melanomas were also tested for comparison. All survival curves were
analyzed using the linear quadratic (LQ) model. Specific parameters for
the intrinsic radiosensitivity (alpha-component, SF2), for the capacity of
repair of DNA damage (beta-component), as well as the alpha/beta ratio
were calculated. RESULTS: After single-dose irradiation a wide range in
the values of the alpha- and beta-component was obtained for both primary
and metastatic uveal melanomas, which resulted in a wide range of
alpha/beta ratios. In contrast, calculations based on split-dose data,
with which the beta-component could be estimated independent of the
alpha-component, indicated that estimates for the capacity of sublethal
DNA damage repair was very similar in all cell lines. This indicated that
intrinsic factors dominated the radiosensitivity of these cell lines.
Split-dose irradiation had little influence on the intrinsic
radiosensitivity (alpha-component), but cell survival increased for all
cell lines. For the two cutaneous melanomas comparable split-dose results
were obtained. CONCLUSIONS: For both primary and metastatic uveal melanoma
cell lines, data from single and fractionated doses indicate large
variations in radiosensitivity, which are mainly dominated by the
intrinsic radiosensitivities. Doses of approximately 8 Gy in five
fractions would be sufficient to eradicate 10(9) cells (approximately 1
cm3) of the most radioresistant tumor cell lines, but this schedule is an
overkill for the radiosensitive tumor cell lines. Based on specific
morphologic and histologic tumor markers, more individualized dose
fractionation schedules could improve the therapeutic ratio for uveal
melanomas