Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Study protocol

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)

Authors: 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

Published in: BMC Cancer | Issue 1/2016

Login to get access

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).
Literature
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.CrossRefPubMed
2.
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.CrossRef
3.
Whitfield GA, Kennedy SR, Djoukhadar IK, Jackson A. Imaging and target volume delineation in glioma. Clin Oncol (R Coll Radiol). 2014;26:364–76.CrossRef
4.
Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010;96:325–7.CrossRefPubMed
5.
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.CrossRefPubMed
6.
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.CrossRefPubMed
7.
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.CrossRefPubMed
8.
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.CrossRefPubMed
9.
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.CrossRefPubMed
10.
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.
11.
Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22:633–8.CrossRefPubMed
12.
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.CrossRefPubMed
13.
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.CrossRefPubMed
14.
Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008;70:1350–60.CrossRefPubMed
15.
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.CrossRefPubMedPubMedCentral
16.
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.CrossRefPubMed
17.
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.CrossRefPubMedPubMedCentral
18.
19.
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.CrossRefPubMed
20.
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.CrossRefPubMedPubMedCentral
21.
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.CrossRefPubMed
22.
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.CrossRefPubMed
23.
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.CrossRefPubMed
24.
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.CrossRefPubMed
25.
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.CrossRefPubMed
26.
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.CrossRefPubMed
27.
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.CrossRefPubMed
28.
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.CrossRefPubMed
29.
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.CrossRefPubMed
30.
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.CrossRefPubMed
31.
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.CrossRefPubMed
32.
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.PubMed
33.
Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103–15.CrossRefPubMed
34.
Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. USA: John Wiley & Sons; 1980.
35.
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.PubMed
36.
Weller M, Wick W. Neuro-oncology in 2013: improving outcome in newly diagnosed malignant glioma. Nat Rev Neurol. 2014;10:68–70.CrossRefPubMed
37.
Seystahl K, Wick W, Weller M. Therapeutic options in recurrent glioblastoma - An update. Crit Rev Oncol Hematol. 2016;99:389–408.CrossRefPubMed
38.
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.CrossRefPubMed
39.
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.CrossRefPubMed
Metadata
Title
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)
Authors
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
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2806-z

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Debate

Primary extramammary invasive Paget’s vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

Research article

Reduced mRNA expression levels of NFE2L2 are associated with poor outcome in breast cancer patients

Case report

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

Research article

Pursuing equity in cancer care: implementation, challenges and preliminary findings of a public cancer referral center in rural Rwanda

Research article

Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy

Study protocol

Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits