title: Prognostic value of radiobiological hypoxia during fractionated irradiation for local tumor control.
abstract: OBJECTIVE
  Previous experiments showed that the fraction of radiobiologically hypoxic tumor cells (rHF) in un-treated tumors did not accurately predict local tumor control after fractionated irradiation. Thus, the prognostic value of rHF determined during fractionated irradiation was investigated.
  
  
  METHODS
  Six human squamous cell carcinoma lines were transplanted into nude mice and then irradiated with 15 fractions over 3 weeks. Thereafter, single dose irradiation under normal and clamped blood flow was given. Local tumor control rates were used to calculate the rHF and the TCD₅₀, i.e., the radiation dose necessary to control 50% of the tumors, after single dose irradiation. These values were compared with the in parallel determined TCD₅₀ after 30 fractions in 6 weeks.
  
  
  RESULTS
  The rHF after 15 fractions varied between 28% and 100%. No correlation was found with the TCD₅₀ after 30 fractions in 6 weeks. Single dose top-up TCD₅₀ under ambient and clamp conditions after 15 fractions significantly correlated with TCD₅₀ after 30 fractions in 6 weeks.
  
  
  CONCLUSIONS
  rHF after 15 fractions is not a prognostic parameter for the outcome after fractionated irradiation. In contrast, the radiobiological parameters number of tumor stem cells, intrinsic radiosensitivity, and number of radiobiologically hypoxic tumor cells appear promising to predict outcome after fractionated irradiation.
authors.affiliation: Department of Radiation Oncology and OncoRay, National Center for Radiation Research in Oncology, Dresden, Germany. Daniel.Zips@uniklinikum-dresden.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.forename: Simon
authors.initials: S
authors.lastname: Böke
authors.forename: Theresa
authors.initials: T
authors.lastname: Kroeber
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinzer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brüchner
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002477:Cells / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D011897:Random Allocation; D014183:Transplantation, Heterologous; D014965:X-Rays