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

Abstract

Purpose: 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. Experimental Design: 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 betweenT 2 or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/hATP 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.Location, histologic grade, and tumor volume are three wellestablished predictors of clinical outcome for soft tissue sarcomas (STS) in humans and dogs (1 -3). These factors, however, do not adequately identify patients who are at the highest risk for development of metastatic disease. Approximately half of the patients diagnosed with high-grade sarcomas will eventually develop metastases (4), but currently, there is no established test to distinguish which patients in this group are at highest risk. In addition, variation among pathologists leads to disagreement up to 25% of the time when staging sarcomas (4). For these reasons, imaging is being used more frequently to stage tumors in the clinic.Magnetic resonance imaging (MRI) is used routinely to assess the characteristics and anatomic extent of tumors. Several groups have reported that contrast-enhanced MRI is of prognostic value for survival (5) and local changes in sarcomas in response to therapy (6). Additionally, T 2 relaxation time and phosphorous magnetic resonance spectroscopy (P-31MRS) variables including intracellular pH (pHi) have been associated with the percentage of necrosis and duration of local tumor control following thermo...

Imaging Tumor Metabolism Using In Vivo Magnetic Resonance Spectroscopy

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Chromatin: a capacitor of acetate for integrated regulation of gene expression and cell physiology

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Molecular imaging for personalized cancer care

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