title: Significant dose can be lost by extended delivery times in IMRT with x rays but not high-LET radiations.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48201, USA. joinerm@wayne.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.forename: Nagaraju
authors.initials: N
authors.lastname: Mogili
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
authors.forename: Jay
authors.initials: J
authors.lastname: Burmeister
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D009369:Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods*