P-31 MAGNETIC-RESONANCE SPECTROSCOPY AS PREDICTOR OF CLINICAL-RESPONSE IN HUMAN EXTREMITY SARCOMAS TREATED BY SINGLE-DOSE TNF-ALPHA PLUS MELPHALAN ISOLATED LIMB PERFUSION

Irresectable extremity sarcomas are large (grade II/III) tumors requir ing amputation of the limb for local control, Limb salvage can be achi eved by isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha), interferon-gamma and melphalan, To obtain insight into t he effects of single dose ILP on extremity tumors, phosphate metabolis m was monitored by P-31 magnetic resonance spectroscopy (MRS) using th e chemical shift imaging (CST) technique, 2D CSI was used in combinati on with a slice select gradient in the third dimension to obtain true 3D localization, Spectral maps obtained prior to ILP revealed reductio ns in phosphocreatine (PCr) level and increases in phosphomonoester (P ME) and phosphodiester (PDE) in tumor compared with muscle tissue, ILP treated tumors showed highly divergent changes in P-i while PME decre ased in all cases (n=11), Tumor volume, unchanged on day 8 after ILP, was decreased by 58+/-29% (mean+/-SD) at 2 months, Linear regression a nalysis revealed correlation between the changes in tumor metabolites measured on day 8, with percent volume decrease (P-i: r=-0.88, p<0.001 ) and percent necrosis at resection (PME:r=-0.79, p-0.01), Correlation between pretreatment spectra and effectiveness of ILP treatment was n ot found, It is concluded that a single ILP with TNF-alpha+melphalan i nduced changes in tumor metabolite levels (measured on day 8) that ref lect treatment efficacy, P-31 MRS can thus provide information facilit ating the decision as to when to remove tumor (residue) and, in the ca se where tumor remains inoperable, whether or not to apply additional therapy.