Exploratory Analysis of Serial 18F-fluciclovine PET-CT and Multiparametric MRI during Chemoradiation for Glioblastoma.

Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) shows preferential glioma uptake but there is little data on how uptake correlates with post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) activity during adjuvant treatment. This pilot study aimed to compare 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM), and in a parallel pre-clinical GBM model, to investigate correlation between 18F-fluciclovine uptake, MRI findings, and tumour biology. 18F-fluciclovine-PET-computed tomography (PET-CT) and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. MRI volumes were manually contoured; PET volumes were defined using semi-automatic thresholding. The similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary was measured using the Dice similarity coefficient (DSC). CT-2A tumour-bearing mice underwent MRI and 18F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. 6 patients were recruited (GBM 1-6) and grouped according to overall survival (OS)-short survival (GBM-SS, median OS 249 days) and long survival (GBM-LS, median 903 days). For GBM-SS, PET tumour volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM-LS, Gd-T1 and DCE-MRI were greater than PET. Tumour-specific 18F-fluciclovine uptake on pre-clinical PET-CT corresponded to immunostaining for Ki-67, nestin and ASCT2. Results suggest volumes of 18F-fluciclovine-PET activity beyond that depicted by DCE-MRI and Gd-T1 are associated with poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed 18F-fluciclovine uptake reflected biologically active tumour.

Volumetric and dosimetric impact of post-surgical MRI-guided radiotherapy for glioblastoma: A pilot study.

Objectives: Glioblastoma (GBM) radiotherapy (RT) target delineation requires MRI, ideally concurrent with CT simulation (pre-RT MRI). Due to limited MRI availability, <72 h post-surgery MRI is commonly used instead. Whilst previous investigations assessed volumetric differences between post-surgical and pre-RT delineations, dosimetric impact remains unknown. We quantify volumetric and dosimetric impact of using post-surgical MRI for GBM target delineation. Methods: Gross tumour volumes (GTVs) for five GBM patients receiving chemo-RT with post-surgical and pre-RT MRIs were delineated by three independent observers. Planning target volumes (PTVs) and RT plans were generated for each GTV. Volumetric and dosimetric differences were assessed through: absolute volumes, volume-distance histograms and dose-volume histogram statistics. Results: Post-surgical MRI delineations had significantly (p < 0.05) larger GTV and PTV volumes (median 16.7 and 64.4 cm3, respectively). Post-surgical RT plans, applied to pre-RT delineations, had significantly decreased (p < 0.01) median PTV doses (ΔD99% = -8.1 Gy and ΔD95% = -2.0 Gy). Median organ-at-risk (OAR) dose increases (brainstem ΔD5% =+0.8, normal brain mean dose =+2.9 and normal brain ΔD10% = 5.3 Gy) were observed. Conclusion: Post-surgical MRI delineation significantly impacted RT planning, with larger normal-appearing tissue volumes irradiated and increased OAR doses, despite a reduced coverage of the pre-RT defined target. Advances in knowledge: We believe this is the first investigation assessing the dosimetric impact of using post-surgical MRI for GBM target delineation. It highlights the potential of significantly degraded RT plans, showing the clinical need for dedicated MRI for GBM RT.

Patient position verification in magnetic-resonance imaging only radiotherapy of anal and rectal cancers.

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-only treatment pathways require either the MR-simulation or synthetic-computed tomography (sCT) as an alternative reference image for cone beam computed tomography (CBCT) patient position verification. This study assessed whether using T2 MR or sCT as CBCT reference images introduces systematic registration errors as compared to CT for anal and rectal cancers. MATERIALS AND METHODS: A total of 32 patients (18 rectum,14 anus) received pre-treatment CT- and T2 MR- simulation. Routine treatment CBCTs were acquired. sCTs were generated using a validated research model. The local clinical registration protocol, using a grey-scale registration algorithm, was performed for 216 CBCTs using CT, MR and sCT as the reference image. Linear mixed effects modelling identified systematic differences between modalities. RESULTS: Systematic translation and rotation differences to CT for MR were -0.3 to + 0.3 mm and -0.1 to 0.4° for anal cancers and -0.4 to 0.0 mm and 0.0 to 0.1° for rectal cancers, and for sCT were -0.4 to + 0.8 mm, -0.1 to 0.2° for anal cancers and -0.6 to + 0.2 mm, -0.1 to + 0.1° for rectal cancers. CONCLUSIONS: T2 MR or sCT can successfully be used as reference images for anal and rectal cancer CBCT position verification with systematic differences to CT <±1 mm and <±0.5°. Clinical enabling of alternative modalities as reference images by vendors is required to reduce challenges associated with their use.

IPEM Topical Report: an international IPEM survey of MRI use for external beam radiotherapy treatment planning.

Introduction/Background. Despite growing interest in magnetic resonance imaging (MRI), integration in external beam radiotherapy (EBRT) treatment planning uptake varies globally. In order to understand the current international landscape of MRI in EBRT a survey has been performed in 11 countries. This work reports on differences and common themes identified.Methods. A multi-disciplinary Institute of Physics and Engineering in Medicine working party modified a survey previously used in the UK to understand current practice using MRI for EBRT treatment planning, investigate how MRI is currently used and managed as well as identify knowledge gaps. It was distributed electronically within 11 countries: Australia, Belgium, Denmark, Finland, France, Italy, the Netherlands, New Zealand, Sweden, the UK and the USA.Results. The survey response rate within the USA was <1% and hence these results omitted from the analysis. In the other 10 countries the survey had a median response rate of 77% per country. Direct MRI access, defined as either having a dedicated MRI scanner for radiotherapy (RT) or access to a radiology MRI scanner, varied between countries. France, Italy and the UK reported the lowest direct MRI access rates and all other countries reported direct access in ≥82% of centres. Whilst ≥83% of centres in Denmark and Sweden reported having dedicated MRI scanners for EBRT, all other countries reported ≤29%. Anatomical sites receiving MRI for EBRT varied between countries with brain, prostate, head and neck being most common. Commissioning and QA of image registration and MRI scanners varied greatly, as did MRI sequences performed, staffing models and training given to different staff groups. The lack of financial reimbursement for MR was a consistent barrier for MRI implementation for RT for all countries and MR access was a reported important barrier for all countries except Sweden and Denmark.Conclusion. No country has a comprehensive approach for MR in EBRT adoption and financial barriers are present worldwide. Variations between countries in practice, equipment, staffing models, training, QA and MRI sequences have been identified, and are likely to be due to differences in funding as well as a lack of consensus or guidelines in the literature. Access to dedicated MR for EBRT is limited in all but Sweden and Denmark, but in all countries there are financial challenges with ongoing per patient costs. Despite these challenges, significant interest exists in increasing MR guided EBRT planning over the next 5 years.

Feasibility of magnetic resonance imaging-only rectum radiotherapy with a commercial synthetic computed tomography generation solution.

BACKGROUND AND PURPOSE: Synthetic computed tomography (sCT) images enable magnetic resonance (MR)-based dose calculations. This work investigated whether a commercially available sCT generation solution was suitable for accurate dose calculations and position verification on patients with rectal cancer. MATERIAL AND METHODS: For twenty rectal cancer patients computed tomography (CT) images were rigidly registered to sCT images. Clinical volumetric modulated arc therapy plans were recalculated on registered CT and sCT images. Dose deviations were determined through gamma and voxelwise analysis. The impact on position verification was investigated by identifying differences in translations and rotation between cone-beam CT (CBCT) to CT and CBCT to sCT registrations. RESULTS: Across twenty patients, within a threshold of 90% of the prescription dose, a gamma analysis (2%, 2 mm) mean pass rate of 95.2 ±â€¯4.0% (±1 σ ) and mean dose deviation of -0.3 ±â€¯0.2% of prescription dose were obtained. The mean difference of translations and rotations over ten patients (76 CBCTs) was <1 mm and <0.5° in all directions. In the sole posterior-anterior direction a mean systematic shift of 0.7 ±â€¯0.6 mm was found. CONCLUSIONS: Accurate MR-based dose calculations using a commercial sCT generation method were clinically feasible for treatment of rectal cancer patients. The accuracy of position verification was clinically acceptable. However, before clinical implementation future investigations will be performed to determine the origin of the systematic shift.