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Extracellular pH and P-31 Magnetic Resonance Spectroscopic Variables are Related to Outcome in Canine Soft Tissue Sarcomas Treated with Thermoradiotherapy

Authors' Affiliations: ¹ Departments of Radiation Oncology, Biostatistics and Bioinformatics, and Radiology, Duke University Medical Center, Durham, North Carolina; ² College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; and ³ School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts

Requests for reprints: Mark W. Dewhirst, Department of Radiation Oncology, Box 3455, Duke University Medical Center, Durham, NC 27710. Phone: 919-684-4180; Fax: 919-684-8718; E-mail: dewhi001{at}mc.duke.edu.

Purpose: The objective was to test whether tumor pH and ³¹P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy.

Experimental Design: Forty-two dogs with evaluable ³¹P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T₂ 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 cm³) 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 T₂ or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/ßATP 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.