Significant dose can be lost by extended delivery times in IMRT with x rays but not high-LET radiations

Purpose: To experimentally simulate IMRT delivery using two human cell models in vitro and test the hypothesis that a loss in effective dose resulting from the prolongation of megavoltage x-ray treatment delivery time would be greatly reduced in corresponding IMRT simulations using higher-LET radiation. Methods: The effect of prolonging the delivery time of a treatment fraction was investigated in vitro using human PC-3 prostate and HGL21 glioblastoma tumor cell lines. Cells were irradiated with x rays from a conventional linear accelerator or with neutrons from a clinical d(48.5) + Be radiotherapy beam and maintained at 37 degrees C throughout. The delivery time for six closely spaced doses, simulating six multiple-port segments, was varied from acute to 60 min for x-ray irradiation, and acute to 120 min for neutron irradiation. Cell survival was measured following summed doses for the six segments of 0.5-6 Gy for x rays and 0.16-2 Gy for neutrons, covering the most likely range of dose per fraction used in clinical radiotherapy. Results: Prolonging x-ray delivery time (from initiation of segment 1 to initiation of segment 6) from 5 to 45 min resulted in a loss in effective total dose (in equivalent 2 Gy multifraction treatments) of 5.6% in the PC-3 cell line and 11.7% in the HGL21 cell line. More clinically common prolongations of 5-30 and 5-15 min resulted in effective dose reductions of 3.8% and 1.7% for PC-3, and 7.3% and 2.9% for HGL21. A loss of less than 0.5% in effective dose was observed for prolongations up to 45 min of similarly effective neutron irradiation of PC-3 and HGL21 cells. Conclusions: Prolonged delivery times of photon fractions could have a significant impact on treatment outcome especially for tumors with a low alpha/beta ratio and short repair halftime. These effects are significant at delivery times commonly associated with IMRT and are variable with cell type. X-ray IMRT should therefore always be planned to minimize dose-fraction delivery time. However, if IMRT treatments are delivered with high-LET radiation, this considerably reduces the dependence of the biological effect on fraction delivery time even out to 2 h. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3425792]