title: Extracellular pH and P-31 magnetic resonance spectroscopic variables are related to outcome in canine soft tissue sarcomas treated with thermoradiotherapy.
abstract: OBJECTIVE
  The objective was to test whether tumor pH and (31)P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy.
  
  
  METHODS
  Forty-two dogs with evaluable (31)P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T(2) relaxation times, intracellular pH, and selected phosphometabolite ratios were examined for correlation with clinical outcome.
  
  
  RESULTS
  From 39 dogs, pHe was a predictor of metastasis-free survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS) with (HR, 0.36; P = 0.013). Tumor volume (>19 cm(3)) was related to MFS (HR, 2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P = 0.03). There was no association between T(2) or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/betaATP ratio were identified as significant predictors for MFS, with (HR, 2.66; P = 0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR, 2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24; P = 0.017).
  
  
  CONCLUSIONS
  pHe was predictive of metastasis and OS in canine spontaneous sarcomas. To our knowledge, this is the first time that pHe has been shown to be predictive of clinical outcome. The results suggest that additional studies should be considered evaluating the prognostic significance of this variable. Phospholipid resonances, related to membrane metabolism, were related to clinical outcome, confirming recent results reported in human patients with soft tissue sarcomas treated with thermoradiotherapy.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Michaël
authors.initials: M
authors.lastname: Lora-Michiels
authors.forename: Daohai
authors.initials: D
authors.lastname: Yu
authors.forename: Linda
authors.initials: L
authors.lastname: Sanders
authors.forename: Jean M
authors.initials: JM
authors.lastname: Poulson
authors.forename: Chieko
authors.initials: C
authors.lastname: Azuma
authors.forename: Beth
authors.initials: B
authors.lastname: Case
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Donald E
authors.initials: DE
authors.lastname: Thrall
authors.forename: H Cecil
authors.initials: HC
authors.lastname: Charles
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010759:Phosphorus Isotopes; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D010759:Phosphorus Isotopes