title: Exploratory study of the prognostic value of microenvironmental parameters during fractionated irradiation in human squamous cell carcinoma xenografts.
abstract: OBJECTIVE
  To explore the prognostic value of microenvironmental parameters for local tumor control determined before and during fractionated irradiation.
  
  
  METHODS
  Six human squamous cell carcinoma (hSCC) lines were transplanted subcutaneously into the right hind leg of nude mice. Tumors were irradiated with 30 fractions within 6 weeks. Local tumor control was determined 120 days after irradiation. Radiation response was quantified as dose to cure 50% of tumors (TCD(50)). In parallel, untreated and irradiated tumors were excised after injection of pimonidazole (hypoxia marker) and Hoechst 33342 (perfusion marker) for histological evaluation.
  
  
  RESULTS
  Pimonidazole hypoxia decreased during fractionated irradiation in the majority of tumor lines. Fraction of perfused vessels and vascular area showed modest changes during fractionated irradiation. Histological parameters before treatment and after three and five fractions did not significantly correlate with TCD(50) after irradiation with 30 fractions within 6 weeks (p > 0.05). Hypoxic volume and perfused vessels after 10 fractions showed a significant association with local tumor control after fractionated irradiation (p = 0.018 and p = 0.019, respectively). None of these parameters remained statistically significant when the p value was adjusted for multiple comparisons.
  
  
  CONCLUSIONS
  The results from this exploratory study suggest that determination of microenvironmental parameters during treatment provides better prognostic information for the outcome after fractionated radiotherapy than pretreatment parameters, which warrants further investigation and confirmation in experimental and clinical studies.
authors.affiliation: OncoRay-National Centre for Radiation Research in Oncology, Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. ala.yaromina@tu-dresden.de
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Theresa
authors.initials: T
authors.lastname: Kroeber
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinzer
authors.forename: Simon
authors.initials: S
authors.lastname: Boeke
authors.forename: Howard
authors.initials: H
authors.lastname: Thames
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D019583:Dose Fractionation, Radiation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009593:Nitroimidazoles / Q000494:pharmacology; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole