Dose-painted volumetric modulated arc therapy of high-grade glioma using 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine positron emission tomography.

OBJECTIVE To determine whether dose painting with volumetric modulated arc therapy for high-grade gliomas using 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-FDOPA) positron emission tomography (PET) could achieve dose-escalated coverage of biological target volumes (BTVs) without increasing the dose to cranial organs at risk (OARs). METHODS 10 patients with high-grade gliomas underwent CT, MRI, and 18F-FDOPA PET/CT images for post-operative radiation therapy planning. Two volumetric modulated arc therapy plans were retrospectively generated for each patient: a conventional plan with 60 Gy in 30 fractions to the planning target volume delineated on MRI and a dose-escalated plan with a maximum dose of 80 Gy in 30 fractions to BTVs. BTVs were created by thresholding 18F-FDOPA PET/CT uptake using a linear quadratic model that assumed tracer uptake was linearly related to tumour cell density. The maximum doses and equivalent uniform doses of OARs were compared. RESULTS The median volume of the planning target volume receiving at least 95% of the prescribed dose (V 95%) was 99.6% with and 99.5% without dose painting. The median V 95% was >99.2% for BTVs. The maximum doses and equivalent uniform doses to the OARs did not differ significantly between the conventional and dose-painted plans. CONCLUSION Using commercially available treatment planning software, dose painting for high-grade gliomas was feasible with good BTV coverage and no significant change in the dose to OARs. ADVANCES IN KNOWLEDGE A novel treatment planning strategy was used to achieve dose painting for gliomas with BTVs obtained from 18F-FDOPA PET/CT using a radiobiological model.

[1]  Cristiana Maurella,et al.  Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma , 2017, Oncotarget.

[2]  Jacob G. Scott,et al.  A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. , 2017, The Lancet. Oncology.

[3]  James A. Purdy,et al.  Phase I three-dimensional conformal radiation dose escalation study in newly diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03. , 2009, International journal of radiation oncology, biology, physics.

[4]  Wei Chen,et al.  18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[6]  Uwe Haberkorn,et al.  Intra-individual comparison of ¹⁸F-FET and ¹⁸F-DOPA in PET imaging of recurrent brain tumors. , 2014, Neuro-oncology.

[7]  Alan Nichol,et al.  High-grade glioma radiation therapy target volumes and patterns of failure obtained from magnetic resonance imaging and 18F-FDOPA positron emission tomography delineations from multiple observers. , 2013, International journal of radiation oncology, biology, physics.

[8]  Shin Jung,et al.  Pathologic analysis of glioblastoma via multiple stereotactic biopsies of active tumor and necrosis. , 2011, Oncology reports.

[9]  I. Gibbs,et al.  Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. , 2018, Neurosurgery.

[10]  Thomas Czech,et al.  Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  Joseph O Deasy,et al.  The use and QA of biologically related models for treatment planning: short report of the TG-166 of the therapy physics committee of the AAPM. , 2012, Medical physics.

[12]  Charles Mayo,et al.  Radiation dose-volume effects of optic nerves and chiasm. , 2009, International journal of radiation oncology, biology, physics.

[13]  C C Ling,et al.  Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. , 2000, International journal of radiation oncology, biology, physics.

[14]  Maria Werner-Wasik,et al.  Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. , 2004, International journal of radiation oncology, biology, physics.

[15]  E. Bar,et al.  Glioblastoma, Cancer Stem Cells and Hypoxia , 2011, Brain pathology.

[16]  N. Dowson,et al.  Increasing feasibility and utility of (18)F-FDOPA PET for the management of glioma. , 2015, Nuclear medicine and biology.

[17]  A. Ahnesjö,et al.  Dose painting by numbers based on retrospectively determined recurrence probabilities. , 2017, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  F. Lieberman,et al.  Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial , 2017, JAMA.

[19]  N. Shah,et al.  Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume , 2016, Radiation oncology.

[20]  R. Komotar,et al.  The role of brachytherapy in the treatment of glioblastoma multiforme , 2017, Neurosurgical Review.

[21]  L. Bogner,et al.  A Biologically Adapted Dose-Escalation Approach, Demonstrated for 18F-FET-PET in Brain Tumors , 2008, Strahlentherapie und Onkologie.

[22]  M. Goitein,et al.  Fitting of normal tissue tolerance data to an analytic function. , 1991, International journal of radiation oncology, biology, physics.

[23]  J. Barnholtz-Sloan,et al.  CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013. , 2016, Neuro-oncology.

[24]  X. Li,et al.  An estimation of radiobiologic parameters from clinical outcomes for radiation treatment planning of brain tumor. , 2006, International journal of radiation oncology, biology, physics.

[25]  Deric M. Park,et al.  Improving the radiosensitivity of radioresistant and hypoxic glioblastoma. , 2010, Future oncology.

[26]  Mark Muzi,et al.  Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  G. Stoffels,et al.  Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas , 2012, Strahlentherapie und Onkologie.

[28]  S. Lam,et al.  Patient and treatment factors associated with survival among adult glioblastoma patients: A USA population-based study from 2000–2010 , 2015, Journal of Clinical Neuroscience.

[29]  Yue Cao,et al.  Concurrent Temozolomide and Dose-Escalated Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma , 2011, Clinical Cancer Research.

[30]  N Satyamurthy,et al.  Regioselective radiofluorodestannylation with [18F]F2 and [18F]CH3COOF: a high yield synthesis of 6-[18F]Fluoro-L-dopa. , 1992, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.

[31]  Charles Mayo,et al.  Radiation associated brainstem injury. , 2010, International journal of radiation oncology, biology, physics.

[32]  M. Bernaudin,et al.  [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[33]  E. Mackenzie,et al.  Multimodal imaging based on MRI and PET reveals [18F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[34]  Ian Law,et al.  Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. , 2016, Neuro-oncology.

[35]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[36]  A. Grosu,et al.  Radiotherapy for High-Grade Gliomas , 2004, Strahlentherapie und Onkologie.

[37]  T. Cloughesy,et al.  Impact of 3,4-Dihydroxy-6-18F-Fluoro-l-Phenylalanine PET/CT on Managing Patients with Brain Tumors: The Referring Physician's Perspective , 2012, The Journal of Nuclear Medicine.

[38]  Steven D Chang,et al.  Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. , 2017, International journal of radiation oncology, biology, physics.

[39]  M. Aznar,et al.  Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer. , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[40]  Val J Lowe,et al.  Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. , 2013, Neuro-oncology.

[41]  Vincent Gregoire,et al.  Molecular imaging-based dose painting: a novel paradigm for radiation therapy prescription. , 2011, Seminars in radiation oncology.

[42]  Søren M Bentzen,et al.  Theragnostic imaging for radiation oncology: dose-painting by numbers. , 2005, The Lancet. Oncology.

[43]  Z. Moravek,et al.  18F-FET-PET-Based Dose Painting by Numbers with Protons , 2010, Strahlentherapie und Onkologie.

[44]  P. Lambin,et al.  Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy – the influence of the choice of the reference region and conversion function , 2017, Acta oncologica.

[45]  N. Bleehen,et al.  A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. , 1991, British Journal of Cancer.

[46]  Junia C Costa,et al.  Patterns of failure for patients with glioblastoma following O-(2-[18F]fluoroethyl)-L-tyrosine PET- and MRI-guided radiotherapy. , 2017, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.