Purpose: This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome. Experimental Design: Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival. Results: Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (P = 0.015) and 0.68 (P = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (P < 0.002) and 0.44 to 0.55 (P < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and 31 P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor. Conclusions: This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas. Numerous phase III clinical trials have shown that thermor-adiotherapy is superior to radiotherapy alone for achieving local tumor control and, in some cases, improving survival (1 -6). It is well known that hyperthermia changes tumor oxygenation, inhibits DNA damage repair, and is directly cytotoxic (7, 8). The effects described above are strongly dependent on temperature and duration of heat exposure, but which effect dominates in improving tumor control with thermoradiotherapy is not known. In preclinical models, mild to moderate heating (41-43jC) leads to increased perfusion and oxygenation, whereas higher thermal exposures can cause vascular damage and hypoxia (8). Presumably, this latter effect would be deleterious to optimal thermoradiotherapy response, but there are no definitive clinical studies showing this.Previous work with canine sarcomas have reported improved oxygenation following a single hyperthermia treatment when median temperatures were <44jC (9) and that changes in oxygenation can persist throughout a course of fractionated thermoradiotherapy (10). Milligan and Panjehpour (11) reported that perfusion was improved throughout a course of thermoradiotherapy in dogs with mast cell tumors. These data support the notion that part of the effect that mild hyperthermi...

Supplementary Data from Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy

<div>Abstract<p><b>Purpose:</b> This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome.</p><p><b>Experimental Design:</b> Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival.</p><p><b>Results:</b> Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (<i>P</i> = 0.015) and 0.68 (<i>P</i> = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (<i>P</i> < 0.002) and 0.44 to 0.55 (<i>P</i> < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and ³¹P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor.</p><p><b>Conclusions:</b> This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas.</p></div>