title: Dose-rate effects in external beam radiotherapy redux.
abstract: Recent developments in external beam radiotherapy, both in technical advances and in clinical approaches, have prompted renewed discussions on the potential influence of dose-rate on radio-response in certain treatment scenarios. We consider the multiple factors that influence the dose-rate effect, e.g. radical recombination, the kinetics of sublethal damage repair for tumors and normal tissues, the difference in alpha/beta ratio for early and late reacting tissues, and perform a comprehensive literature review. Based on radiobiological considerations and the linear-quadratic (LQ) model we estimate the influence of overall treatment time on radio-response for specific clinical situations. As the influence of dose-rate applies to both the tumor and normal tissues, in oligo-fractionated treatment using large doses per fraction, the influence of delivery prolongation is likely important, with late reacting normal tissues being generally more sensitive to the dose-rate effect than tumors and early reacting tissues. In conventional fractionated treatment using 1.8-2Gy per fraction and treatment times of 2-1 min, the influence of dose-rate is relatively small. Lastly, the dose-rate effect in external beam radiotherapy is governed by the overall beam-on-time, not by the average linac dose-rate, nor by the instantaneous dose-rate within individual linac pulses which could be as high as 3 x 10(6)MU/min.
authors.affiliation: Varian Medical Systems, Palo Alto, CA, USA. lingc@mskcc.org
authors.forename: C Clifton
authors.initials: CC
authors.lastname: Ling
authors.forename: Leo E
authors.initials: LE
authors.lastname: Gerweck
authors.forename: Marco
authors.initials: M
authors.lastname: Zaider
authors.forename: Ellen
authors.initials: E
authors.lastname: Yorke
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage