ABSTRACT: Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas, but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven. We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma.
This open, randomised, phase 2 trial was undertaken in 24 centres in six countries. 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS, cranial nerves, or eyes, aged 18-75 years, and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were centrally randomly assigned by computer to receive four courses of either methotrexate 3.5 g/m(2) on day 1 (n=40) or methotrexate 3.5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice a day on days 2-3 (n=39). Both regimens were administered every 3 weeks and were followed by whole-brain irradiation. The primary endpoint was complete remission rate after chemotherapy. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00210314.
All randomly assigned participants were analysed. After chemotherapy, seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission, with a complete remission rate of 18% (95% CI 6-30) and 46% (31-61), respectively, (p=0.006). Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response, with an overall response rate of 40% (25-55) and 69% (55-83), respectively, (p=0.009). Grade 3-4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects (three vs one).
In patients aged 75 years and younger with primary CNS lymphoma, the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone.
Swiss Cancer League.
The Lancet 09/2009; 374(9700):1512-20. · 38.28 Impact Factor
ABSTRACT: Contrast-enhanced magnetic resonance (MR) imaging with gadolinium-based contrast agents is widely used for the detection of cerebral metastases with standard contrast agents. Newer developments in MR contrast agents have led to a higher relaxivity and/or concentration for these agents.
To assess the effectiveness of a standard dose of 1.0 M gadobutrol compared with a standard dose of gadopentetate dimeglumine for the MR detection of brain metastases.
27 patients with at least one cerebral metastasis were examined twice with contrast-enhanced MR imaging, using gadobutrol at 0.1 ml/kg and gadopentetate dimeglumine at 0.2 ml/kg (i.e., identical gadolinium dosage of 0.1 mmol/kg bodyweight). The interval between examinations was 18 hours, and the order of injection was fully randomized. Images were acquired using a three-dimensional (3D) fast gradient echo sequence, and evaluated in blinded fashion by two experienced neuroradiologists in consensus in terms of the total number of lesions detected at each examination in each patient and qualitatively in terms of the lesion conspicuity observed.
A total of 67 lesions were detected after gadobutrol compared with 65 lesions detected after gadopentetate dimeglumine. In two patients, a lesion was seen only after gadobutrol. Qualitative comparison of images revealed improved lesion conspicuity after gadobutrol in 10/27 cases compared with 0/27 cases after gadopentetate dimeglumine, and equivalent conspicuity in 17/27 cases (P=0.002, gadobutrol vs. gadopentetate dimeglumine).
At equal gadolinium dosage, gadobutrol appears to offer significant advantages over gadopentetate dimeglumine for the visualization of brain metastases, with particular benefit for improving the conspicuity of detected lesions.
Acta Radiologica 08/2009; 50(8):933-40. · 1.37 Impact Factor
ABSTRACT: Magnetic Resonance Angiography (MRA) is one of the most practical diagnostic imaging modalities in the field of neurovascular imaging where risks associated with catheter angiography are high. Evaluation of the extracranial supraortic vessels, and in particular the carotid arteries, is the major field of application for MRA. Before the development of rapid contrast-enhanced (CE) acquisition sequences, the major limitations of MRA pertaining to the carotid arteries was the limited volume of study when 3D time-of-flight (TOF) images were acquired, and the saturation effects together with low spatial resolution and movement artifacts when 2D TOF images were acquired. Although technical improvements helped overcome some of these limitations, MRA was still not considered a valid diagnostic alternative to DSA for the evaluation of carotid artery stenosis until the advent of CE acquisitions. Most published studies on CE-MRA of the carotid arteries have been performed with standard gadolinium-based chelates which have similar r1 relaxivity values. Newer gadolinium chelates such as gadobenate dimeglumine (Multihance, Gd-BOPTA, Bracco) have higher intravascular r1 relaxivity than other agents such as Gd-DTPA. This leads to higher vascular peak enhancement of longer duration which has proven beneficial for improving vascular contrast. CE-MRA is today considered a highly suitable replacement for conventional MRA techniques and DSA for the evaluation of extracranial carotid artery disease. Compared with unenhanced MRA sequences, CE-MRA permits complete and reliable evaluation of the internal carotid artery from the bifurcation to the intracranial segment. Moreover, the technique offers better overall accuracy for the depiction of tight stenosis and more confident diagnosis of real carotid occlusion versus subocclusive stenosis.
European Radiology 11/2006; 16 Suppl 7:M27-34. · 3.22 Impact Factor