PREDICTING HUMAN TUMOR RESPONSE BY 31P MRS

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DESCRIPTION: This application from CCCMH, Detroit, Michigan. The 31-P Magnetic Resonance Spectroscopy (MRS) of human cancers in vivo typically have metabolic characteristics which differ from those of normal tissues. These include elevations of phosphomonoesters (PME), phosphodiesters (PDE), and cellular pH, and dimished phosphocreatine (PCr). These characteristics have been shown to provide useful prognostic indices and predictors of sensitivity to radiotherapy combined with hyperthermia in soft tissue sarcomas. This background indicates that it would now be appropriate to examine the clinical utility of MRS in the management of cancer patients. The study proposed in this application is a cooperative prospective trial in a large number of patients with types of cancers especially well suited to address this issue. This proposal is one of 8 Interactive R01 applications from 8 institutions collaborating to study over 1400 patients with non- Hodgkin's lymphomas, locally advanced primary breast cancers, soft tissue sarcomas, and carcinomas of the head and neck. Careful attention will be paid to patient selection, protocol management, technical quality control and group statistical analysis. State-of-the-art techniques have been or will be established at all institutions, to include: dual tuned 1H 31-P surface coils needed to access the wide variety of anatomic locations of these cancers; proton decoupling of 31- P to distinguish individual components of phospholipid metabolites; image guided 3 dimensional chemical shift imaging to accurately localize 31-P MR spectra to tumor masses; absolute quantitation of metabolites; and pattern recognition of spectra. The applicants will test the hypothesis that the in vivo 31-P Mr spectrum can predict the sensitivity or resistance to treatment by correlating the initial response to metabolic features in the baseline spectrum and to changes that occur in the spectrum early after the initiation of treatment. The applicants will also test the hypothesis that 31-P MRS contains prognostic information by correlating disease-free survival in responders, and where feasible overall survival, to metabolic features in the baseline and followup spectra. This study will establish standards for cooperative MRS trials in other cancers and clinical settings, and will pave the way for clinical trials in which MRS could be used to intervene in the selection of treatment regimens in individual cancer patients.