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31 P magnetic resonance spectroscopy as predictor of clinical response in human extremity sarcomas treated by single dose TNF‐α+ melphalan isolated limb perfusion
Author(s) -
Sijens Paul E.,
Dijk Pieter Van,
Oudkerk Matthijs,
Eggermont Alexander M. M.
Publication year - 1995
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1940080506
Subject(s) - melphalan , phosphocreatine , chemistry , perfusion , tumor necrosis factor alpha , sarcoma , magnetic resonance imaging , nuclear medicine , metabolite , medicine , nuclear magnetic resonance , chemotherapy , pathology , radiology , physics , energy metabolism
Irresectable extremity sarcomas are large (grade II/III) tumors requiring amputation of the limb for local control. Limb salvage can be achieved by isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF‐α), interferon‐γ and melphalan. To obtain insight into the effects of single dose ILP on extremity tumors, phosphate metabolism was monitored by 31 P magnetic resonance spectroscopy (MRS) using the chemical shift imaging (CSI) technique. 2D CSI was used in combination with a slice select gradient in the third dimension to obtain true 3D localization. Spectral maps obtained prior to ILP revealed reductions in phosphocreatine (PCr) level and increases in phosphomonoester (PME) and phosphodiester (PDE) in tumor compared with muscle tissue. ILP treated tumors showed highly divergent changes in P i while PME decreased 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 analysis 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 not found. It is concluded that a single ILP with TNF‐α+melphalan induced changes in tumor metabolite levels (measured on day 8) that reflect treatment efficacy. 31 P MRS can thus provide information facilitating the decision as to when to remove tumor (residue) and, in the case where tumor remains inoperable, whether or not to apply additional therapy.