Previous studies of murine tumors has suggested that it may be feasible to predict tumor response or sensitivity to anti-neoplastic therapy based on changes in metabolites that can be detected noninvasively by 31P NMR spectroscopy. Preliminary clinical studies from numerous institutions, studying a wide range of tumors, with a plethora of varied techniques, have suggested that although the spectral changes detected in murine and clinical studies are different, nevertheless, it may be feasible to predict clinical response on the basis of spectral changes. This study proposes to study a single tumor, extremity sarcomas, in detail, and determine whether 31P NMR spectroscopy can be used as an a priori or early predictor of tumor response. This study will utilize volume localization (chemical shift imaging) to limit spectral contamination. To enhance spectral resolution, 1H spin decoupling will be used; previous murine and clinical studies have indicated that resolving the PME and PDE resonances into individual peaks, may yield further information, than the data that can be otherwise obtained. Absolute quantitation of the various metabolites, with correction for the effects of B1 inhomogenity, coil loading, T1 effects, will be done. The data will be directly related to clinical outcome. As a single institution study, we will have ready access to all clinical data, i.e. pathology at the time of surgery (including % necrosis), outcome, disease free interval, response rate, and other tumor markers. The data will be obtained using identical techniques to other groups, including Duke University. Thus the data can be used to independently assess whether the pretreatment parameters that they have found to predict response, can be corroborated at our institution, and their can verify the validity of predictors found in this study. In addition to addressing the important question of whether 31P NMR spectroscopy can be used to predict tumor response, this study will also provide insight into phospholipid metabolism by monitoring changes in phospholipid anabolites and catabolites. Phospholipid metabolism may be an important factor in determining tumor growth, cell cycle distribution, metastases and other important facets of tumor biology, and the NMR studies may yield new insights into this area.
|Zakian, Kristen L; Shukla-Dave, Amita; Meyers, Paul et al. (2003) Identification of prognostic markers in bone sarcomas using proton-decoupled phosphorus magnetic resonance spectroscopy. Cancer Res 63:9042-7|