Treatment planning Investigation on the role of integrated PET/MRI for target volume definition and radiotherapy planning in patients with high grade glioma Pierina Navarria a,⇑ , Giacomo Reggiori a , Federico Pessina b , Anna Maria Ascolese a , Stefano Tomatis a , Pietro Mancosu a , Francesca Lobefalo a , Elena Clerici a , Egesta Lopci c , Alberto Bizzi d , Marco Grimaldi d , Arturo Chiti c , Matteo Simonelli e , Armando Santoro e , Lorenzo Bello b , Marta Scorsetti a a Radiotherapy and Radiosurgery Department; b Neurosurgical Oncology Department; c Nuclear Medicine Department; d Neuroradiology Department; and e Oncology and Hematology Department, Istituto Clinico Humanitas Cancer Center, Milan, Italy article info Article history: Received 30 March 2014 Received in revised form 8 September 2014 Accepted 9 September 2014 Available online 9 October 2014 Keywords: High grade glioma Radiotherapy-planning MET-PET abstract Purpose: To evaluate the impact of fluid-attenuated-inversion-recovery MRI (FLAIR/MRI) and Carbon- 11-labeled-methionine PET (11C-MET-PET) on high grade glioma (HGG) tumor volume delineation for radiotherapy planning. Material and methods: Sixty-nine patients with HGG were evaluated. The clinical target volumes (CTV1, generated by adding a 10 mm margin to FLAIRMRI area, CTV2 by adding a 20 mm margin to enhanced T1MRI) and biological target volume (BTV) were delineated on pre-operative MRI images and 11CMETPET respectively. Results: The overlap between CTV1 and CTV2 showed a low correlation between the two volumes with CTV1 not always fully included into the CTV2. In all cases the whole BTV was included into the CTV1, while in 35/69 patients (50%) part of BTV was outside the CTV2 despite larger margins were added. In all cases recurrences were within the CTV1 volume and in 19/38 (50%) partially outside the CTV2. In all patients relapse corresponded to the BTV area. Conclusions: Our data suggest that the target volume definition using FLAIR–MRI is more adequate com- pared to enhanced T1MRI. 11C-METPET uptake could help identify microscopic residual areas. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 112 (2014) 425–429 The current standard of care for newly diagnosed glioblastoma (GBM) is maximal safe resection, followed by adjuvant radiother- apy and chemotherapy [1]. The results, however, have not been satisfying [2], and the main site of treatment failure is usually included in the high-dose region [3,4]. To improve local control and survival, a clearer identification of the volume at the greatest risk of recurrence is required, while the radiation exposure of healthy brain tissue should be reduced. The critical point is reach- ing a correct tumor delineation, based on imaging. Over the past decade considerable improvements have been made by combining Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) in the radiotherapy planning process [5]. The contrast enhancement T1-weighted-MRI usually outlines the most aggres- sive tumor area where the blood brain barrier is disrupted. In this sequence however the main tumor infiltrating border is not visible thus leading to an underestimation of the target volume. Fluid-attenuated-inversion-recovery (FLAIR) is a T2-weighted MR sequence with the suppression of Cerebral Spinal Fluid (CSF) sig- nal. FLAIR provides a better delineation of the lesion once the con- founding effect of CSF has been removed. Therefore this sequence allows a more accurate definition of the infiltrating microscopic disease growing outside the enhanced area on T1 MRI [6–8]. More recently, the use of Positron-Emission-Tomography (PET) with different radio-labeled tracers has been investigated for tumor delineation. Particularly, initial reports suggest that Car- bon-11-labeled-methionine PET (11C-MET-PET) improves diag- nostic accuracy for both diagnosis and treatment planning of brain tumors. This tracer is characterized by a high uptake by the tumor cells and very limited by the healthy brain tissue, providing with very useful functional informations. In fact, while MRI gives a morphological tumor delineation [9,10], 11C-MET-PET provides with a complementary metabolic information allowing a more pre- cise viable tumor cell identification. The literature data concerning the definition of the treatment volumes based on PET and T1MRI images are controversial. Grosu et al., integrating MET-PET into the planning procedure, improved target volumes for both menin- giomas and gliomas by enlarging them [11]. Another MET-PET planning study performed by Matsuo et al. [12] found the best http://dx.doi.org/10.1016/j.radonc.2014.09.004 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Istituto Clinico Humanitas Cancer Center, Radiation Oncology, Rozzano, Italy. E-mail address: piera.navarria@cancercenter.humanitas.it (P. Navarria). Radiotherapy and Oncology 112 (2014) 425–429 Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com