Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts

<p>Abstract</p> <p>Background</p> <p>Particle irradiation was established at the University of Heidelberg 2 years ago. To date, more than 400 patients have been treated including patients with primary brain tumors. In malignant glioma (WHO IV) patients, two clinical trials have been set up-one investigating the benefit of a carbon ion (18 GyE) vs. a proton boost (10 GyE) in addition to photon radiotherapy (50 Gy), the other one investigating reirradiation with escalating total dose schedules starting at 30 GyE. In atypical meningioma patients (WHO °II), a carbon ion boost of 18 GyE is applied to macroscopic tumor residues following previous photon irradiation with 50 Gy.</p> <p>This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas.</p> <p>Methods</p> <p>33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0.</p> <p>Results</p> <p>Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient.</p> <p>Conclusions</p> <p>Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials.</p

Volumetry of [11C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme

We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [(11)C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM).MET-PET and contrast-enhanced MRI with Gd-DTPA were performed in 12 uniformly pretreated patients with recurrent GBM. To calculate the volumes in cubic centimetres, a threshold-based volume-of-interest (VOI) analysis of the metabolically active tumour volume (MET uptake indexes of > or = 1.3 and > or = 1.5) and of the area of Gd-DTPA enhancement was performed after coregistration of all images.In all patients, the metabolically active tumour volume as shown using a MET uptake index of > or = 1.3 was larger than the volume of Gd-DTPA enhancement (30.2 + or - 22.4 vs. 13.7 + or - 10.6 cm(3); p = 0.04). Metabolically active tumour volumes as shown using MET uptake indexes of > or =1.3 and > or = 1.5 and the volumes of Gd-DTPA enhancement showed a positive correlation (r = 0.76, p = 0.003, for an index of > or =1.3, and r = 0.74, p = 0.005, for an index of > or =1.5).The present data suggest that in patients with recurrent GBM the metabolically active tumour volume may be substantially underestimated by Gd-DTPA enhancement. The findings support the notion that complementary information derived from MET uptake and Gd-DTPA enhancement may be helpful in developing individualized, patient-tailored therapy strategies in patients with recurrent GBM