Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) - protocol of a randomized phase II trial (NOA 10/ARO 2013-1)

Oliver Oehlke, Michael Mix, Erika Graf, Tanja Schimek-Jasch, Ursula Nestle, Irina Götz, Sabine Schneider-Fuchs, Astrid Weyerbrock, Irina Mader, Brigitta G Baumert, Susan C Short, Philipp T Meyer, Wolfgang A Weber, Anca-Ligia Grosu, Oliver Oehlke, Michael Mix, Erika Graf, Tanja Schimek-Jasch, Ursula Nestle, Irina Götz, Sabine Schneider-Fuchs, Astrid Weyerbrock, Irina Mader, Brigitta G Baumert, Susan C Short, Philipp T Meyer, Wolfgang A Weber, Anca-Ligia Grosu

Abstract

Background: The higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV). A small single-center non-randomized prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET was integrated in target volume delineation, in comparison to patients treated based on CT/MRI alone.

Methods: This protocol describes a prospective, open label, randomized, multi-center phase II trial designed to test if radiotherapy target volume delineation based on FET-PET leads to improvement in progression free survival (PFS) in patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared to target volume delineation based on T1Gd-MRI. The target sample size is 200 randomized patients with a 1:1 allocation ratio to both arms. The primary endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans and/or biopsy/surgery if suspicious of progression. Secondary endpoints include overall survival (OS), locally controlled survival (time to local progression or death), volumetric assessment of GTV delineated by either method, topography of progression in relation to MRI- or PET-derived target volumes, rate of long term survivors (>1 year), localization of necrosis after re-irradiation, quality of life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety of FET-application in AA-PET imaging and toxicity of re-irradiation.

Discussion: This is a protocol of a randomized phase II trial designed to test a new strategy of radiotherapy target volume delineation for improving the outcome of patients with recurrent GBM. Moreover, the trial will help to develop a standardized methodology for the integration of AA-PET and other imaging biomarkers in radiation treatment planning.

Trial registration: The GLIAA trial is registered with ClinicalTrials.gov ( NCT01252459 , registration date 02.12.2010), German Clinical Trials Registry ( DRKS00000634 , registration date 10.10.2014), and European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date 27.02.2012).

Keywords: Amino-acid PET; Re-irradiation; Recurrent glioblastoma; T1-Gd-MRI.

Figures

Fig. 1
Fig. 1
Flowchart of the GLIAA trial. AA-PET = amino acid positron emission tomography; MRI = magnetic resonance imaging; FET = O-(2-[18F]fluoroethyl)-L-tyrosine; Gd = gadolinium
Fig. 2
Fig. 2
a and b Definition of GTV according to contrast enhancement in T1-MRI (green) and increased FET uptake (Tumor to Background Ratio >1.8, red). c and d Resulting PTV according to study arm A (FET-PET, pink). e and f Resulting PTV according to treatment arm B (MRI, pink). The corresponding treatment plan according to Arm A is shown in (g), and the corresponding treatment plan for Arm B is shown in (h). Isodose distribution is displayed as follows: 95 % isodose line (yellow), 80 % isodose line (green), and 50 % isodose line (blue). Source and copyright: Center for Diagnostic and Therapeutic Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany

References

    1. Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer. 2007;7:949–60. doi: 10.1038/nrc2288.
    1. Burnet NG, Jena R, Burton KE, Tudor GS, Scaife JE, Harris F, Jefferies SJ. Clinical and practical considerations for the use of intensity-modulated radiotherapy and image guidance in neuro-oncology. Clin Oncol (R Coll Radiol) 2014;26:395–406. doi: 10.1016/j.clon.2014.04.024.
    1. Whitfield GA, Kennedy SR, Djoukhadar IK, Jackson A. Imaging and target volume delineation in glioma. Clin Oncol (R Coll Radiol) 2014;26:364–76. doi: 10.1016/j.clon.2014.04.026.
    1. Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010;96:325–7. doi: 10.1016/j.radonc.2010.08.001.
    1. Niyazi M, Brada M, Chalmers AJ, Combs SE, Erridge SC, Fiorentino A, et al. ESTRO-ACROP guideline “target delineation of glioblastomas”. Radiother Oncol. 2016;118:35–42. doi: 10.1016/j.radonc.2015.12.003.
    1. Grosu AL, Weber W, Feldmann HJ, Wuttke B, Bartenstein P, Gross MW, et al. First experience with I-123-alpha-methyl-tyrosine spect in the 3-D radiation treatment planning of brain gliomas. Int J Radiat Oncol Biol Phys. 2000;47:517–26. doi: 10.1016/S0360-3016(00)00423-5.
    1. Grosu AL, Feldmann H, Dick S, Dzewas B, Nieder C, Gumprecht H, et al. Implications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas. Int J Radiat Oncol Biol Phys. 2002;54:842–54. doi: 10.1016/S0360-3016(02)02984-X.
    1. Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, et al. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:64–74. doi: 10.1016/j.ijrobp.2005.01.045.
    1. Grosu AL, Weber WA, Franz M, Stärk S, Piert M, Thamm R, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:511–9. doi: 10.1016/j.ijrobp.2005.01.056.
    1. Munck Af Rosenschold P, Costa J, Engelholm SA, Lundemann MJ, Law I, Ohlhues L, Engelholm S. Impact of [18F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma. Neuro-Oncology. 2015;17.
    1. Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22:633–8. doi: 10.1097/WCO.0b013e328332363e.
    1. Hutterer M, Hattingen E, Palm C, Proescholdt MA, Hau P. Current standards and new concepts in MRI and PET response assessment of antiangiogenic therapies in high-grade glioma patients. Neuro Oncol. 2015;17:784–800. doi: 10.1093/neuonc/nou322.
    1. Huang RY, Rahman R, Ballman KV, Felten SJ, Anderson SK, Ellingson BM, et al. The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab. Clin Cancer Res. 2016;22:575–81. doi: 10.1158/1078-0432.CCR-14-3040.
    1. Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008;70:1350–60. doi: 10.1016/j.ijrobp.2007.08.015.
    1. Lawrence YR, Li XA, el Naqa I, Hahn CA, Marks LB, Merchant TE, Dicker AP. Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76:S20–7. doi: 10.1016/j.ijrobp.2009.02.091.
    1. Combs SE, Gutwein S, Thilmann C, Huber P, Debus J, Schulz-Ertner D. Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme. J Neurooncol. 2005;74:167–71. doi: 10.1007/s11060-004-2463-y.
    1. Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, et al. Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol. 2010;28:3048–53. doi: 10.1200/JCO.2009.25.6941.
    1. Thorwarth D. Functional imaging for radiotherapy treatment planning: current status and future directions-a review. Br J Radiol. 2015;88:20150056. doi: 10.1259/bjr.20150056.
    1. Weber WA, Grosu AL, Czernin J. Technology Insight: advances in molecular imaging and an appraisal of PET/CT scanning. Nat Clin Pract Oncol. 2008;5:160–70. doi: 10.1038/ncponc1041.
    1. la Fougère C, Suchorska B, Bartenstein P, Kreth FW, Tonn JC. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncol. 2011;13:806–19. doi: 10.1093/neuonc/nor054.
    1. Plotkin M, Gneveckow U, Meier-Hauff K, Amthauer H, Feussner A, Denecke T, et al. 18F-FET PET for planning of thermotherapy using magnetic nanoparticles in recurrent glioblastoma. Int J Hyperthermia. 2006;22:319–25. doi: 10.1080/02656730600734128.
    1. Miwa K, Matsuo M, Shinoda J, Oka N, Kato T, Okumura A, Ueda T, et al. Simultaneous integrated boost technique by helical tomotherapy for the treatment of glioblastoma multiforme with 11C-methionine PET: report of three cases. J Neurooncol. 2008;87:333–9. doi: 10.1007/s11060-008-9519-3.
    1. Rickhey M, Koelbl O, Eilles C, Bogner L. A biologically adapted dose-escalation approach, demonstrated for 18F-FET-PET in brain tumors. Strahlenther Onkol. 2008;184:536–42. doi: 10.1007/s00066-008-1883-6.
    1. Lee IH, Piert M, Gomez-Hassan D, Junck L, Rogers L, Hayman J, et al. Association of 11C-methionine PET uptake with site of failure after concurrent temozolomide and radiation for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2009;73:479–85. doi: 10.1016/j.ijrobp.2008.04.050.
    1. Vees H, Senthamizhchelvan S, Miralbell R, Weber DC, Ratib O, Zaidi H. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients. Eur J Nucl Med Mol Imaging. 2009;36:182–93. doi: 10.1007/s00259-008-0943-6.
    1. Weber DC, Casanova N, Zilli T, Buchegger F, Rouzaud M, Nouet P, et al. Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study. Radiother Oncol. 2009;93:586–92. doi: 10.1016/j.radonc.2009.08.043.
    1. Niyazi M, Geisler J, Siefert A, Schwarz SB, Ganswindt U, Garny S, et al. FET-PET for malignant glioma treatment planning. Radiother Oncol. 2011;99:44–8. doi: 10.1016/j.radonc.2011.03.001.
    1. Piroth MD, Pinkawa M, Holy R, Klotz J, Schaar S, Stoffels G, et al. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study. Strahlenther Onkol. 2012;188:334–9. doi: 10.1007/s00066-011-0060-5.
    1. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–72. doi: 10.1200/JCO.2009.26.3541.
    1. Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, et al. The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer. 2006;42:55–64. doi: 10.1016/j.ejca.2005.06.022.
    1. Nieder C, Astner ST, Mehta MP, Grosu AL, Molls M. Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma. Am J Clin Oncol. 2008;31:300–5. doi: 10.1097/COC.0b013e31815e3fdc.
    1. Korn EL, Arbuck SG, Pluda JM, Simon R, Kaplan RS, Christian MC. Clinical trial designs for cytostatic agents: are new approaches needed? J Clin Oncol. 2001;19:265–72.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103–15. doi: 10.2307/2529712.
    1. Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. USA: John Wiley & Sons; 1980.
    1. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16:139–44.
    1. Weller M, Wick W. Neuro-oncology in 2013: improving outcome in newly diagnosed malignant glioma. Nat Rev Neurol. 2014;10:68–70. doi: 10.1038/nrneurol.2013.268.
    1. Seystahl K, Wick W, Weller M. Therapeutic options in recurrent glioblastoma - An update. Crit Rev Oncol Hematol. 2016;99:389–408. doi: 10.1016/j.critrevonc.2016.01.018.
    1. Oppitz U, Maessen D, Zunterer H, Richter S, Flentje M. 3D-recurrence-patterns of glioblastomas after CT-planned postoperative irradiation. Radiother Oncol. 1999;53:53–7. doi: 10.1016/S0167-8140(99)00117-6.
    1. Galldiks N, Langen KJ, Pope WB. From the clinician’s point of view - What is the status quo of positron emission tomography in patients with brain tumors? Neuro Oncol. 2015;17:1434–44. doi: 10.1093/neuonc/nov118.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다