title: Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment.
abstract: OBJECTIVE
  The objectives of this study were to evaluate effects of hyperthermia on tumor oxygenation, extracellular pH (pHe), and blood flow in 13 dogs with spontaneous soft tissue sarcomas prior to and after local hyperthermia.
  
  
  METHODS
  Tumor pO2 was measured using an Eppendorf polarographic device, pHe using interstitial electrodes, and blood flow using contrast-enhanced magnetic resonance imaging (MRI).
  
  
  RESULTS
  There was an overall improvement in tumor oxygenation observed as an increase in median pO2 and decrease in hypoxic fraction (% of pO2 measurements <5 mm Hg) at 24-h post hyperthermia. These changes were most pronounced when the median temperature (T50) during hyperthermia treatment was less than 44 degrees C. Tumors with T50 > 44 degrees C were characterized by a decrease in median PO2 and an increase in hypoxic fraction. Similar thermal dose-related changes were observed in tumor perfusion. Perfusion was significantly higher after hyperthermia. Increases in perfusion were most evident in tumors with T50 < 44 degrees C. With T50 > 44 degrees C, there was no change in perfusion after hyperthermia. On average, pHe values declined in all animals after hyperthermia, with the greatest reduction seen for larger T50 values.
  
  
  CONCLUSIONS
  This study suggests that hyperthermia has biphasic effects on tumor physiologic parameters. Lower temperatures tend to favor improved perfusion and oxygenation, whereas higher temperatures are more likely to cause vascular damage, thus leading to greater hypoxia. While it has long been recognized that such effects occur in rodent tumors, this is the first report to tie such changes to temperatures achieved during hyperthermia in the clinical setting. Furthermore, it suggests that the thermal threshold for vascular damage is higher in spontaneous tumors than in more rapidly growing rodent tumors.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: J M
authors.initials: JM
authors.lastname: Poulson
authors.forename: A A
authors.initials: AA
authors.lastname: Gaskin
authors.forename: D E
authors.initials: DE
authors.lastname: Thrall
authors.forename: R L
authors.initials: RL
authors.lastname: Page
authors.forename: H C
authors.initials: HC
authors.lastname: Charles
authors.forename: J R
authors.initials: JR
authors.lastname: MacFall
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
authors.forename: R E
authors.initials: RE
authors.lastname: Meyer
authors.forename: D M
authors.initials: DM
authors.lastname: Prescott
authors.forename: T V
authors.initials: TV
authors.lastname: Samulski
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy*
chemical_list: D010100:Oxygen