title: Quantification of tumor reoxygenation during accelerated radiation therapy.
abstract: OBJECTIVE
  To determine the effect of accelerated fractionated radiation therapy on the reoxygenation of chronic hypoxic tumor cells by means of a three-dimensional Monte Carlo simulation.
  
  
  METHODS
  Tumor growth (cell cycle time [Tc] of 2 or 5 days), irradiation (alpha = 0.3 Gy-1, alpha/beta = 10 Gy), oxygen tension (oxygen enhancement ratio of 3.0), capillary network distortion, and shrinkage of a small (10(4)-cell) tumor were modeled on a workstation. Conventional (2 Gy delivered five times per week), accelerated (1.6 Gy delivered twice a day for 5 d/wk), and split-course (1.6 Gy delivered twice a day for 5 d/wk with a break in week 3) radiation therapies were simulated with total doses of 50-70 Gy.
  
  
  RESULTS
  Tumors grew in cords with a central necrotic area surrounded by hypoxic cells (hypoxic fraction, 25%). If undisturbed tumor shrinkage occurred, complete reoxygenation took 2 1/2 weeks for accelerated, 3-5 weeks for split-course, or 4-6 weeks for conventional radiation therapy. If shrinkage was prevented, the hypoxic fraction rose to 90%-100% at 2-3 weeks. In the shrinking, reoxygenation tumors with a Tc of 2 days, accelerated radiation therapy increased tumor control by 40%-80% over the control with conventional radiation therapy. With split-course therapy, this advantage was lost at doses below 70 Gy. Shrinking tumors with a Tc of 5 days were all controlled with 50 Gy.
  
  
  CONCLUSIONS
  Fast-growing tumors that reoxygenate by shrinking are especially sensitive to acceleration and treatment breaks.
authors.affiliation: Department of Radiotherapy, University of Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kocher
authors.forename: H
authors.initials: H
authors.lastname: Treuer
authors.forename: R P
authors.initials: RP
authors.lastname: Müller
mesh_terms: D002455:Cell Division; D003198:Computer Simulation; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010100:Oxygen / Q000378:metabolism*; D011879:Radiotherapy Dosage
chemical_list: D010100:Oxygen