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
Radiation Oncology
Published in: Radiation Oncology 1/2016

Open Access 01-12-2016 | Research

Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume

Authors: Marc D. Piroth, Norbert Galldiks, Michael Pinkawa, Richard Holy, Gabriele Stoffels, Johannes Ermert, Felix M. Mottaghy, N. Jon Shah, Karl-Josef Langen, Michael J. Eble

Published in: Radiation Oncology | Issue 1/2016

Login to get access

Abstract

Background

O-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition.

Methods

A relapse pattern analysis was performed in 13 glioblastoma patients treated with radiochemotherapy within a prospective phase-II-study between 2008 and 2009. Radiotherapy was performed as an integrated-boost intensity-modulated radiotherapy (IB-IMRT). The prescribed dose was 72 Gy for the boost target volume, based on baseline FET-PET (FET-1) and 60 Gy for the MRI-based (MRI-1) standard target volume. The single doses were 2.4 and 2.0 Gy, respectively. Location and volume of recurrent tumors in FET-2 and MRI-2 were analyzed related to initial tumor, detected in baseline FET-1. Variable target volumes were created theoretically based on FET-1 to optimally cover recurrent tumor.

Results

The tumor volume overlap in FET and MRI was poor both at baseline (median 12 %; range 0–32) and at time of recurrence (13 %; 0–100). Recurrent tumor volume in FET-2 was localized to 39 % (12–91) in the initial tumor volume (FET-1). Over the time a shrinking (mean 12 (5–26) ml) and shifting (mean 6 (1–10 mm) of the resection cavity was seen. A simulated target volume based on active tumor in FET-1 with an additional safety margin of 7 mm around the FET-1 volume covered recurrent FET tumor volume (FET-2) significantly better than a corresponding target volume based on contrast enhancement in MRI-1 with a same safety margin of 7 mm (100 % (54–100) versus 85 % (0–100); p < 0.01). A simulated planning target volume (PTV), based on FET-1 and additional 7 mm margin plus 5 mm margin for setup-uncertainties was significantly smaller than the conventional, MR-based PTV applied in this study (median 160 (112–297) ml versus 231 (117–386) ml, p < 0.001).

Conclusions

In this small study recurrent tumor volume in FET-PET (FET-2) overlapped only to one third with the boost target volume, based on FET-1. The shrinking and shifting of the resection cavity may have an influence considering the limited overlap of initial and relapse tumor volume. A simulated target volume, based on FET-1 with 7 mm margin covered 100 % of relapse volume in median and led to a significantly reduced PTV, compared to MRI-based PTVs. This approach may achieve similar therapeutic efficacy but lower side effects offering a broader window to intensify concomitant systemic treatment focusing distant failures.
Literature
1.
Jansen EP, Dewit LG, van Herk M, Bartelink H. Target volumes in radiotherapy for high-grade malignant glioma of the brain. Radiother Oncol. 2000;56(2):151–6.CrossRefPubMed
2.
Halperin EC, Bentel G, Heinz ER, Burger PC. Radiation therapy treatment planning in supratentorial glioblastoma multiforme: an analysis based on post mortem topographic anatomy with CT correlations. Int J Radiat Oncol Biol Phys. 1989;17(6):1347–50.CrossRefPubMed
3.
Lunsford LD, Martinez AJ, Latchaw RE. Magnetic resonance imaging does not define tumor boundaries. Acta Radiol Suppl. 1986;369:154–6.PubMed
4.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. JClinOncol. 2010;28(11):1963–72.CrossRef
5.
Chang EL, Akyurek S, Avalos T, Rebueno N, Spicer C, Garcia J, Famiglietti R, Allen PK, Chao KS, Mahajan A, et al. Evaluation of peritumoral edema in the delineation of radiotherapy clinical target volumes for glioblastoma. Int J Radiat Oncol Biol Phys. 2007;68(1):144–50.CrossRefPubMed
6.
McDonald MW, Shu HK, Curran Jr WJ, Crocker IR. Pattern of failure after limited margin radiotherapy and temozolomide for glioblastoma. Int J Radiat Oncol Biol Phys. 2011;79(1):130–6.CrossRefPubMed
7.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed
8.
Aydin H, Sillenberg I, von Lieven H. Patterns of failure following CT-based 3-D irradiation for malignant glioma. Strahlenther Onkol. 2001;177(8):424–31.CrossRefPubMed
9.
Mason WP, Maestro RD, Eisenstat D, Forsyth P, Fulton D, Laperriere N, Macdonald D, Perry J, Thiessen B, Canadian GBMRC. Canadian recommendations for the treatment of glioblastoma multiforme. Curr Oncol. 2007;14(3):110–7.CrossRefPubMedPubMedCentral
10.
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(1):84–92.CrossRefPubMed
11.
Galldiks N, Langen KJ, Holy R, Pinkawa M, Stoffels G, Nolte KW, Kaiser HJ, Filss CP, Fink GR, Coenen HH, et al. Assessment of treatment response in patients with glioblastoma using O-(2-18 F-fluoroethyl)-L-tyrosine PET in comparison to MRI. J Nucl Med. 2012;53(7):1048–57.CrossRefPubMed
12.
Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M. 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(1):64–74.CrossRefPubMed
13.
Miwa K, Shinoda J, Yano H, Okumura A, Iwama T, Nakashima T, Sakai N. Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study. J Neurol Neurosurg Psychiatry. 2004;75(10):1457–62.CrossRefPubMedPubMedCentral
14.
Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Muller HW, Zilles K, Coenen HH, Langen KJ. O-(2-[18 F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128(Pt 3):678–87.CrossRefPubMed
15.
Piroth MD, Holy R, Pinkawa M, Stoffels G, Kaiser HJ, Galldiks N, Herzog H, Coenen HH, Eble MJ, Langen KJ. Prognostic impact of postoperative, pre-irradiation 18F-Fluoroethyl-L-Tyrosine uptake in glioblastoma patients treated with radiochemotherapy. Radiother Oncol. 2011;99(2):2018–24.
16.
Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, Koutcher JA. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys. 2000;47(3):551–60.CrossRefPubMed
17.
Levivier M, Massager N, Wikler D, Goldman S. Modern multimodal neuroimaging for radiosurgery: the example of PET scan integration. Acta Neurochir Suppl. 2004;91:1–7.PubMed
18.
Rickhey M, Koelbl O, Eilles C, Bogner L. A biologically adapted dose-escalation approach, demonstrated for 18 F-FET-PET in brain tumors. Strahlenther Onkol. 2008;184(10):536–42.CrossRefPubMed
19.
Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, Nouet P, Dipasquale G, Ratib O, Zaidi H, et al. [(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma. Radiat Oncol. 2008;3:44.CrossRefPubMedPubMedCentral
20.
Piroth MD, Pinkawa M, Holy R, Stoffels G, Demirel C, Attieh C, Kaiser HJ, Langen KJ, Eble MJ. Integrated-boost IMRT or 3-D-CRT using FET-PET based auto-contoured target volume delineation for glioblastoma multiforme--a dosimetric comparison. Radiat Oncol. 2009;4:57.CrossRefPubMedPubMedCentral
21.
Grosu AL, Weber WA, Franz M, Stark S, Piert M, Thamm R, Gumprecht H, Schwaiger M, Molls M, Nieder C. 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(2):511–9.CrossRefPubMed
22.
Weber DC, Casanova N, Zilli T, Buchegger F, Rouzaud M, Nouet P, Vees H, Ratib O, Dipasquale G, Miralbell R. Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study. Radiother Oncol. 2009;93(3):586–92.CrossRefPubMed
23.
Lee IH, Piert M, Gomez-Hassan D, Junck L, Rogers L, Hayman J, Ten Haken RK, Lawrence TS, Cao Y, Tsien C. 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(2):479–85.CrossRefPubMed
24.
Niyazi M, Jansen NL, Rottler M, Ganswindt U, Belka C. Recurrence pattern analysis after re-irradiation with bevacizumab in recurrent malignant glioma patients. Radiat Oncol. 2014;9:299.CrossRefPubMedPubMedCentral
25.
Piroth MD, Pinkawa M, Holy R, Klotz J, Schaar S, Stoffels G, Galldiks N, Coenen HH, Kaiser HJ, Langen KJ, 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(4):334–9.CrossRefPubMed
26.
Chan JL, Lee SW, Fraass BA, Normolle DP, Greenberg HS, Junck LR, Gebarski SS, Sandler HM. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002;20(6):1635–42.CrossRefPubMed
27.
Langen KJ, Hamacher K, Weckesser M, Floeth F, Stoffels G, Bauer D, Coenen HH, Pauleit D. O-(2-[18 F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2006;33(3):287–94.CrossRefPubMed
28.
Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, Reifenberger G, Kebir S, Dorn F, Blau T, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18 F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42(5):685–95.CrossRefPubMed
29.
Galldiks N, Stoffels G, Filss C, Rapp M, Blau T, Tscherpel C, Ceccon G, Dunkl V, Weinzierl M, Stoffel M, et al. The use of dynamic O-(2-18 F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro-Oncology. 2015;17(9):1293–300.PubMed
30.
Farace P, Giri MG, Meliado G, Amelio D, Widesott L, Ricciardi GK, Dall’Oglio S, Rizzotti A, Sbarbati A, Beltramello A, et al. Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI. Br J Radiol. 2011;84(999):271–8.CrossRefPubMedPubMedCentral
31.
Minniti G, Amelio D, Amichetti M, Salvati M, Muni R, Bozzao A, Lanzetta G, Scarpino S, Arcella A, Enrici RM. Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiother Oncol. 2010;97(3):377–81.CrossRefPubMed
32.
Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, Klein JC, Herholz K, Heiss WD. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res. 2004;10(21):7163–70.CrossRefPubMed
33.
Pafundi DH, Laack NN, Youland RS, Parney IF, Lowe VJ, Giannini C, Kemp BJ, Grams MP, Morris JM, Hoover JM, et al. Biopsy validation of 18 F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. Neuro-Oncology. 2013;15(8):1058–67.CrossRefPubMedPubMedCentral
34.
Rieken S, Habermehl D, Giesel FL, Hoffmann C, Burger U, Rief H, Welzel T, Haberkorn U, Debus J, Combs SE. Analysis of FET-PET imaging for target volume definition in patients with gliomas treated with conformal radiotherapy. Radiother Oncol. 2013;109(3):487–92.CrossRefPubMed
35.
Popperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18 F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004;31(11):1464–70.CrossRefPubMed
36.
Lee SW, Fraass BA, Marsh LH, Herbort K, Gebarski SS, Martel MK, Radany EH, Lichter AS, Sandler HM. Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999;43(1):79–88.CrossRefPubMed
37.
Oppitz U, Maessen D, Zunterer H, Richter S, Flentje M. 3D-recurrence-patterns of glioblastomas after CT-planned postoperative irradiation. Radiother Oncol. 1999;53(1):53–7.CrossRefPubMed
Metadata
Title
Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume
Authors
Marc D. Piroth
Norbert Galldiks
Michael Pinkawa
Richard Holy
Gabriele Stoffels
Johannes Ermert
Felix M. Mottaghy
N. Jon Shah
Karl-Josef Langen
Michael J. Eble
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2016
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-016-0665-z

Other articles of this Issue 1/2016

Radiation Oncology 1/2016 Go to the issue

Research

A Nomogram to predict parotid gland overdose in head and neck IMRT

Research

Monte Carlo simulation of beam characteristics from small fields based on TrueBeam flattening-filter-free mode

Research

Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03)

Reviewer acknowledgement

Radiation Oncology reviewer acknowledgement 2015

Research

The effect of extremely narrow MLC leaf width on the plan quality of VMAT for prostate cancer

Research

Role of SGK1 for fatty acid uptake, cell survival and radioresistance of NCI-H460 lung cancer cells exposed to acute or chronic cycling severe hypoxia