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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 8/2017

03.03.2017 | Original Article

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

verfasst von: Cornelius Deuschl, Christoph Moenninghoff, Sophia Goericke, Julian Kirchner, Susanne Köppen, Ina Binse, Thorsten D. Poeppel, Harald H. Quick, Michael Forsting, Lale Umutlu, Ken Herrmann, Joerg Hense, Marc Schlamann

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2017

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Abstract

Background

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment.

Methods

Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio.

Results

MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log).

Conclusions

This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.
Literatur
1.
Zurück zum Zitat Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66. doi:10.1016/S1470-2045(09)70025-7.CrossRefPubMed Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66. doi:10.​1016/​S1470-2045(09)70025-7.CrossRefPubMed
2.
Zurück zum Zitat Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol Off J Am Soc Clin Oncol. 1999;17:2572–8.CrossRef Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol Off J Am Soc Clin Oncol. 1999;17:2572–8.CrossRef
4.
Zurück zum Zitat Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:4733–40. doi:10.1200/JCO.2008.19.8721.CrossRef Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:4733–40. doi:10.​1200/​JCO.​2008.​19.​8721.CrossRef
5.
Zurück zum Zitat Wick W, Weller M, van den Bent M, Stupp R. Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:e188–9. doi:10.1200/JCO.2009.26.9027. author reply e90–2.CrossRef Wick W, Weller M, van den Bent M, Stupp R. Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:e188–9. doi:10.​1200/​JCO.​2009.​26.​9027. author reply e90–2.CrossRef
6.
Zurück zum Zitat Wick W, Brandes AA, Gorlia T, Bendszus M, Sahm F, Taal W, et al. EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma. J Clin Oncol 2016;34:(suppl; abstr 2001). Wick W, Brandes AA, Gorlia T, Bendszus M, Sahm F, Taal W, et al. EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma. J Clin Oncol 2016;34:(suppl; abstr 2001).
7.
Zurück zum Zitat Boss A, Bisdas S, Kolb A, Hofmann M, Ernemann U, Claussen CD, et al. Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT. J Nucl Med Off Publ Soc Nucl Med. 2010;51:1198–205. doi:10.2967/jnumed.110.074773. Boss A, Bisdas S, Kolb A, Hofmann M, Ernemann U, Claussen CD, et al. Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT. J Nucl Med Off Publ Soc Nucl Med. 2010;51:1198–205. doi:10.​2967/​jnumed.​110.​074773.
8.
Zurück zum Zitat 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 Off J Am Soc Clin Oncol. 2010;28:1963–72. doi:10.1200/JCO.2009.26.3541.CrossRef 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 Off J Am Soc Clin Oncol. 2010;28:1963–72. doi:10.​1200/​JCO.​2009.​26.​3541.CrossRef
10.
11.
Zurück zum Zitat Hu LS, Eschbacher JM, Dueck AC, Heiserman JE, Liu S, Karis JP, et al. Correlations between perfusion MR imaging cerebral blood volume, microvessel quantification, and clinical outcome using stereotactic analysis in recurrent high-grade glioma. AJNR Am J Neuroradiol. 2012;33:69–76. doi:10.3174/ajnr.A2743.CrossRefPubMed Hu LS, Eschbacher JM, Dueck AC, Heiserman JE, Liu S, Karis JP, et al. Correlations between perfusion MR imaging cerebral blood volume, microvessel quantification, and clinical outcome using stereotactic analysis in recurrent high-grade glioma. AJNR Am J Neuroradiol. 2012;33:69–76. doi:10.​3174/​ajnr.​A2743.CrossRefPubMed
12.
Zurück zum Zitat Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishiwata K, et al. Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg. 2005;103:498–507. doi:10.3171/jns.2005.103.3.0498.CrossRefPubMed Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishiwata K, et al. Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg. 2005;103:498–507. doi:10.​3171/​jns.​2005.​103.​3.​0498.CrossRefPubMed
13.
Zurück zum Zitat Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H, et al. O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med Off Publ Soc Nucl Med. 2011;52:856–64. doi:10.2967/jnumed.110.086645. Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H, et al. O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med Off Publ Soc Nucl Med. 2011;52:856–64. doi:10.​2967/​jnumed.​110.​086645.
14.
Zurück zum Zitat Beppu T, Terasaki K, Sasaki T, Sato Y, Tomabechi M, Kato K, et al. MRI and 11C-methyl-L-methionine PET differentiate bevacizumab true responders after initiating therapy for recurrent glioblastoma. Clin Nucl Med. 2016;41:852–7. doi:10.1097/RLU.0000000000001377.CrossRefPubMed Beppu T, Terasaki K, Sasaki T, Sato Y, Tomabechi M, Kato K, et al. MRI and 11C-methyl-L-methionine PET differentiate bevacizumab true responders after initiating therapy for recurrent glioblastoma. Clin Nucl Med. 2016;41:852–7. doi:10.​1097/​RLU.​0000000000001377​.CrossRefPubMed
16.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. doi:10.1056/NEJMoa043330.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. doi:10.​1056/​NEJMoa043330.CrossRefPubMed
17.
Zurück zum Zitat Delso G, Furst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med Off Publ Soc Nucl Med. 2011;52:1914–22. doi:10.2967/jnumed.111.092726. Delso G, Furst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med Off Publ Soc Nucl Med. 2011;52:1914–22. doi:10.​2967/​jnumed.​111.​092726.
19.
Zurück zum Zitat Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773–82.CrossRefPubMed Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773–82.CrossRefPubMed
20.
Zurück zum Zitat Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25:4714–21. doi:10.1200/JCO.2006.10.5825.CrossRef Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25:4714–21. doi:10.​1200/​JCO.​2006.​10.​5825.CrossRef
21.
Zurück zum Zitat Galldiks N, Ullrich R, Schroeter M, Fink GR, Jacobs AH, Kracht LW. Volumetry of [(11)C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme. Eur J Nucl Med Mol Imaging. 2010;37:84–92. doi:10.1007/s00259-009-1219-5.CrossRefPubMed Galldiks N, Ullrich R, Schroeter M, Fink GR, Jacobs AH, Kracht LW. Volumetry of [(11)C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme. Eur J Nucl Med Mol Imaging. 2010;37:84–92. doi:10.​1007/​s00259-009-1219-5.CrossRefPubMed
23.
24.
Zurück zum Zitat Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, et al. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology. 1998;50:1316–22.CrossRefPubMed Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, et al. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology. 1998;50:1316–22.CrossRefPubMed
25.
Zurück zum Zitat Galldiks N, Kracht LW, Burghaus L, Thomas A, Jacobs AH, Heiss WD, et al. Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging. 2006;33:516–24. doi:10.1007/s00259-005-0002-5.CrossRefPubMed Galldiks N, Kracht LW, Burghaus L, Thomas A, Jacobs AH, Heiss WD, et al. Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging. 2006;33:516–24. doi:10.​1007/​s00259-005-0002-5.CrossRefPubMed
26.
Zurück zum Zitat Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med Off Publ Soc Nucl Med. 2008;49:694–9. doi:10.2967/jnumed.107.048082. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med Off Publ Soc Nucl Med. 2008;49:694–9. doi:10.​2967/​jnumed.​107.​048082.
27.
Zurück zum Zitat Galldiks N, Rapp M, Stoffels G, Fink GR, Shah NJ, Coenen HH, et al. Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]fluoroethyl-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging. 2013;40:22–33. doi:10.1007/s00259-012-2251-4.CrossRefPubMed Galldiks N, Rapp M, Stoffels G, Fink GR, Shah NJ, Coenen HH, et al. Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]fluoroethyl-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging. 2013;40:22–33. doi:10.​1007/​s00259-012-2251-4.CrossRefPubMed
29.
Zurück zum Zitat Radbruch A, Lutz K, Wiestler B, Baumer P, Heiland S, Wick W, et al. Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria. Neuro-Oncology. 2012;14:222–9. doi:10.1093/neuonc/nor200.CrossRefPubMed Radbruch A, Lutz K, Wiestler B, Baumer P, Heiland S, Wick W, et al. Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria. Neuro-Oncology. 2012;14:222–9. doi:10.​1093/​neuonc/​nor200.CrossRefPubMed
30.
Zurück zum Zitat Radbruch A, Fladt J, Kickingereder P, Wiestler B, Nowosielski M, Baumer P, et al. Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence. Neuro-Oncology. 2015;17:151–9. doi:10.1093/neuonc/nou129.CrossRefPubMed Radbruch A, Fladt J, Kickingereder P, Wiestler B, Nowosielski M, Baumer P, et al. Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence. Neuro-Oncology. 2015;17:151–9. doi:10.​1093/​neuonc/​nou129.CrossRefPubMed
31.
Zurück zum Zitat Schmainda KM, Zhang Z, Prah M, Snyder BS, Gilbert MR, Sorensen AG, et al. Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial. Neuro-Oncology. 2015;17:1148–56. doi:10.1093/neuonc/nou364.CrossRefPubMedPubMedCentral Schmainda KM, Zhang Z, Prah M, Snyder BS, Gilbert MR, Sorensen AG, et al. Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial. Neuro-Oncology. 2015;17:1148–56. doi:10.​1093/​neuonc/​nou364.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Kickingereder P, Radbruch A, Burth S, Wick A, Heiland S, Schlemmer HP, et al. MR perfusion-derived hemodynamic parametric response mapping of Bevacizumab efficacy in recurrent glioblastoma. Radiology. 2016;279:542–52. doi:10.1148/radiol.2015151172.CrossRefPubMed Kickingereder P, Radbruch A, Burth S, Wick A, Heiland S, Schlemmer HP, et al. MR perfusion-derived hemodynamic parametric response mapping of Bevacizumab efficacy in recurrent glioblastoma. Radiology. 2016;279:542–52. doi:10.​1148/​radiol.​2015151172.CrossRefPubMed
35.
Zurück zum Zitat Harris RJ, Cloughesy TF, Pope WB, Nghiemphu PL, Lai A, Zaw T, et al. 18F-FDOPA and 18F-FLT positron emission tomography parametric response maps predict response in recurrent malignant gliomas treated with bevacizumab. Neuro-Oncology. 2012;14:1079–89. doi:10.1093/neuonc/nos141.CrossRefPubMedPubMedCentral Harris RJ, Cloughesy TF, Pope WB, Nghiemphu PL, Lai A, Zaw T, et al. 18F-FDOPA and 18F-FLT positron emission tomography parametric response maps predict response in recurrent malignant gliomas treated with bevacizumab. Neuro-Oncology. 2012;14:1079–89. doi:10.​1093/​neuonc/​nos141.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Geist C, et al. 3′-deoxy-3′-18F-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab. J Nucl Med Off Publ Soc Nucl Med. 2012;53:29–36. doi:10.2967/jnumed.111.092387. Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Geist C, et al. 3′-deoxy-3′-18F-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab. J Nucl Med Off Publ Soc Nucl Med. 2012;53:29–36. doi:10.​2967/​jnumed.​111.​092387.
37.
Zurück zum Zitat Kobayashi K, Hirata K, Yamaguchi S, Manabe O, Terasaka S, Kobayashi H, et al. Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients. Eur J Nucl Med Mol Imaging. 2015;42:1071–80. doi:10.1007/s00259-015-3046-1.CrossRefPubMed Kobayashi K, Hirata K, Yamaguchi S, Manabe O, Terasaka S, Kobayashi H, et al. Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients. Eur J Nucl Med Mol Imaging. 2015;42:1071–80. doi:10.​1007/​s00259-015-3046-1.CrossRefPubMed
38.
Zurück zum Zitat Preuss M, Werner P, Barthel H, Nestler U, Christiansen H, Hirsch FW, et al. Integrated PET/MRI for planning navigated biopsies in pediatric brain tumors. Childs Nerv Syst: ChNS Off J Int Soc Pediatr Neurosurg. 2014;30:1399–403. doi:10.1007/s00381-014-2412-9.CrossRef Preuss M, Werner P, Barthel H, Nestler U, Christiansen H, Hirsch FW, et al. Integrated PET/MRI for planning navigated biopsies in pediatric brain tumors. Childs Nerv Syst: ChNS Off J Int Soc Pediatr Neurosurg. 2014;30:1399–403. doi:10.​1007/​s00381-014-2412-9.CrossRef
Metadaten
Titel
Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study
verfasst von
Cornelius Deuschl
Christoph Moenninghoff
Sophia Goericke
Julian Kirchner
Susanne Köppen
Ina Binse
Thorsten D. Poeppel
Harald H. Quick
Michael Forsting
Lale Umutlu
Ken Herrmann
Joerg Hense
Marc Schlamann
Publikationsdatum
03.03.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2017
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3661-0

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