Improved detection of diffuse glioma infiltration with imaging combinations: a diagnostic accuracy study.

BACKGROUND: Surgical resection and irradiation of diffuse glioma are guided by standard MRI: T2/fluid attenuated inversion recovery (FLAIR)-weighted MRI for non-enhancing and T1-weighted gadolinium-enhanced (T1G) MRI for enhancing gliomas. Amino acid PET has been suggested as the new standard. Imaging combinations may improve standard MRI and amino acid PET. The aim of the study was to determine the accuracy of imaging combinations to detect glioma infiltration. METHODS: We included 20 consecutive adults with newly diagnosed non-enhancing glioma (7 diffuse astrocytomas, isocitrate dehydrogenase [IDH] mutant; 1 oligodendroglioma, IDH mutant and 1p/19q codeleted; 1 glioblastoma IDH wildtype) or enhancing glioma (glioblastoma, 9 IDH wildtype and 2 IDH mutant). Standardized preoperative imaging (T1-, T2-, FLAIR-weighted, and T1G MRI, perfusion and diffusion MRI, MR spectroscopy and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET) was co-localized with multiregion stereotactic biopsies preceding resection. Tumor presence in the biopsies was assessed by 2 neuropathologists. Diagnostic accuracy was determined using receiver operating characteristic analysis. RESULTS: A total of 174 biopsies were obtained (63 from 9 non-enhancing and 111 from 11 enhancing gliomas), of which 129 contained tumor (50 from non-enhancing and 79 from enhancing gliomas). In enhancing gliomas, the combination of apparent diffusion coefficient (ADC) with [18F]FET PET (area under the curve [AUC], 95% CI: 0.89, 0.79‒0.99) detected tumor better than T1G MRI (0.56, 0.39‒0.72; P < 0.001) and [18F]FET PET (0.76, 0.66‒0.86; P = 0.001). In non-enhancing gliomas, no imaging combination detected tumor significantly better than standard MRI. FLAIR-weighted MRI had an AUC of 0.81 (0.65-0.98) compared with 0.69 (0.56-0.81; P = 0.019) for [18F]FET PET. CONCLUSION: Combining ADC and [18F]FET PET detects glioma infiltration better than standard MRI and [18F]FET PET in enhancing gliomas, potentially enabling better guidance of local therapy.

A phase I study of monohydroxyethylrutoside in healthy volunteers.

The flavonol monohydroxyethylrutoside (monoHER) has demonstrated protection against doxorubicin-induced cardiotoxicity in in vitro and in vivo studies without affecting the antitumor effect. In the present phase I study, the possible side effects and the pharmacokinetics of monoHER were evaluated in healthy volunteers with the aim to develop a safe and feasible dose to be evaluated in cancer patients treated with doxorubicin. The study was performed as a single blind, randomized trial in healthy volunteers (age between 19 and 56 years). At each dose level, six subjects received monoHER and three placebo. MonoHER was solubilized in 100 ml dextrose 5% and administered as an i.v. infusion in 10 min. The placebo consisted of 100 ml dextrose 5%. The starting dose of monoHER was 100 mg/m(2). Dose escalation by 100% of the preceding dose took place after finishing each dose level until the protecting pharmacokinetic values for C (max) and AUC(infinity) (as observed in mice after 500 mg/kg monoHER i.p.) were reached and/or serious side effects were observed. The dose was escalated up to 1,500 mg/m(2). The mean values of C (max) and AUC(infinity) were 360+/-69.3 microM and 6.8+/-2.1 micromol min/ml, respectively. These values were comparable to the C (max) and AUC(infinity) observed under the protecting conditions in mice. No serious side effects occurred during the entire study. Thus, 1,500 mg/m(2) is a feasible and safe dose to be evaluated in a phase II study to investigate the protective properties of monoHER against doxorubicin-induced cardiotoxicity in cancer patients.