Utility of C-11-methionine PET in a clinical trial of Glivec and hydroxyurea in recurrent glioblastoma (GBM)

Objectives GBM is a highly malignant brain tumor with frequent over-expression of PDGFR and c-KIT expression in endothelial cells. We evaluated the use of C-11-methionine (MET) PET as a biomarker to assess the therapeutic response to a combination therapy (Glivec & Hydroxyurea) in GBM in comparison with Progression Free Survival (PFS) and Overall Survival (OS).

Methods Nineteen patients, 7f/12 m, median age 55 (range 22-72) with histologically confirmed GBM were included after their first recurrence, following surgery, radio- and chemo-therapy with temozolomide or nitrosourea, ECOG score ≤ 2. The primary objective of the clinical component of the Phase II open-label, single arm study was the objective response rate. In addition, patients underwent MET-PET before treatment and at weeks 3, 13, and 25 of therapy. Data were acquired 18-48 min after injection of approx. 400 Mbq MET preceded by 6 hr fasting. Scans were coregistered to each other and contrast-enhanced MRI. Tumor activity was analyzed by10mm spherical VOIs as tumor/reference ratio (T/R) and as active volume (ActVol) above initial half T/R.

Results Changes of T/R at first follow-up were highly correlated with changes at second follow-up (R=0.93, p=0.02). Overall PFS (median 74±39 d) and OS (149±16 d) were short and did not correlate significantly with T/R and ActVol changes. The strongest prognostic MET-PET parameter was ActVol prior to therapy.

Conclusions Treatment response on MET-PET at 3 weeks predicted the response at 13 weeks. Within this small sample and generally short survival times a relation between MET-PET changes and clinical outcome could not be established.