Abstract:Purpose/Objective: Intensity Modulated Radiation Therapy has proven extraordinary capability in physical terms such as target conformity, dose escalation in the target volume and sparing of neighbouring risk structures. But intensity modulation of radiation beams requires sophisticated methods which increase the time of one fraction drastically and therefore lower the dose-rate. Using the step and shoot technology irradiation is performed with a sequence of several subsegments in intervals of some seconds. Complex IMRT-plans result in a pulsed dose delivery consisting of more than hundred subsegments with a fraction time of up to 30 minutes. The radiobiological consequences of this decreased dose-rate and pulsed dose application is still unclear. Their influence on cell survival an cell cycle progression shall be examined. Materials/Methods: Clonogenic survival of human melanoma cells (MeWo) was determined using the colony forming assay. Survival of lymphoblastoid cells (TK6) was examined using the microtiter plate dilution assay. Cell cycle distributions were analysed using one colour flow cytometry. All irradiations were performed with a Siemens linear accelerator PRIMUS at energies of 6 or 15 MeV. In a preliminary series of experiments cells were irradiated in cell culture flasks using 6 different radiation plans simulating a successive decrease of dose-rate and a pulsed dose delivery as it appears in IMRT. In each plan a total dose of 2 Gy was applied, at first in one single pulse, then in two pulses with intervals of 5, 15 and 30 minutes. In the last two plans the dose was delivered in 6 respectively 21 pulses, each in an overall time of 30 minutes. The second experimental series was performed using a new biophysical phantom of cylindrical shape to transfer IMRT-patient plans into an experimental setup (Schaefer et al. submitted an abstract about this phantom and special software). 4 plans of patients with meningeoma, breast cancer and 2 nasopharynx carcinomas were chosen. Cells were irradiated at various points of the plans and survival was analyzed. Results: Preliminary experiments After 12 repetitions the clonogenic survival of MeWo and TK6 increased with the growing number of pulses and growing fraction time. Both cell lines showed risen survival rates. Especially interesting is the difference between plan 2 representing a conventional two field plan and plan 6 beeing closest to the protracted dose application in IMRT. Melanoma cells showed a highly significant increase of survival of 7.03 % (p=0.0002, t-test) and lymphoblasts an increase of survival of 2.24 % (p=0.04, t-test) beeing borderline significant. Cell cycle distributions at various times after irradiation using plan 2 and 6 showed no significant differences. Experiments using patient plans Cells were irradiated at various points of patient plans receiving doses at a range of 0.6 Gy to 2.4 Gy. In comparison to irradiation in a 4-field-box with a dose-rate of 1 Gy/min Melanoma cells showed sigificantly increased cell survival in the IMRT plans with dose rates lower than 0.12 Gy/min. At various doses the survival was significantly higher (about 5 to 7%). Conclusions: With an increasing number of pulses and increasing fraction time both cell lines showed risen survival rates. Cell cycle distributions showed no significant differences after different radiation plans. Fraction time differences seem to be too small to cause any effects in cell cycle progression. Our data indicate that the lowered dose-rate in IMRT has an effect on survival and should be considered in further optimization of IMRT.
Sterzing MD, F,
Radio-biological Investigation of Dose-Rate Effects in Intensity Modulated Radiation Therapy. Radiological Society of North America 2003 Scientific Assembly and Annual Meeting, November 30 - December 5, 2003 ,Chicago IL.
http://archive.rsna.org/2003/3238673.html
