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CORRESPONDENCE
Year : 2013  |  Volume : 9  |  Issue : 4  |  Page : 715-717

The demonstration of extension of high-grade glioma beyond magnetic resonance imaging defined edema by the use of 11 C-methionine positron emission tomography


1 Department of Radiation Oncology, Health Care Global-Bangalore Institute of Oncology, Karnataka, India
2 Department of Orthopedics, Bhagwan Mahaveer Jain Hospital, Bengaluru, Karnataka, India

Date of Web Publication11-Feb-2014

Correspondence Address:
Swaroop Revannasiddaiah
Department of Radiation Oncology, Health Care Global-Bangalore Institute of Oncology, #8 P. Kalinga Rao Road, Sampangiramnagar, Bengaluru - 560 027
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.126464

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 > Abstract 

The use of magnetic resonance imaging (MRI) is the current standard for the delineation of target volumes for high-grade gliomas (HGG). While the peritumoral edema as per T2-weighted (T2W) imaging is utilized as basis to delineate the initial borders of the clinical target volume (CTV), those areas enhancing on T1-weighted (T1W) images with gadolinium contrast (T1-Gd) are considered for treatment with further boost. However, recent data has emerged concerning the use of positron emission tomography (PET) with 11 C-methionine, which seemingly provides additional information beyond MRI. We present the case of a gentleman with an inoperable HGG which was imaged with 11 C-methionine-PET ( 11 C-MET-PET)/CT as well as MRI as part of the radiotherapy treatment planning (RTP) process. The differences noted between the MRI and the PET defined volumes are presented. This being a patient who was not operated, the potentially confounding issue of surgery-induced PET-avidity is absent.

Keywords: High grade gliomas, methionine positron emission tomography, positron emission tomography scan for glioblastoma multiforme, 11 C-methionine positron emission tomography


How to cite this article:
Susheela SP, Revannasiddaiah S, Madhusudhan N, Bijjawara M. The demonstration of extension of high-grade glioma beyond magnetic resonance imaging defined edema by the use of 11 C-methionine positron emission tomography. J Can Res Ther 2013;9:715-7

How to cite this URL:
Susheela SP, Revannasiddaiah S, Madhusudhan N, Bijjawara M. The demonstration of extension of high-grade glioma beyond magnetic resonance imaging defined edema by the use of 11 C-methionine positron emission tomography. J Can Res Ther [serial online] 2013 [cited 2019 Nov 23];9:715-7. Available from: http://www.cancerjournal.net/text.asp?2013/9/4/715/126464


 > Introduction Top


While the advent of magnetic resonance imaging (MRI) has significantly revolutionized target-volume delineation for high-grade glioma (HGG), the overall survival outlook for these patients continues to be dismal. Recent experimentation with imaging modalities such as 11 C-Methionine-positron-emission-tomography ( 11 C-MET-PET) and magnetic resonance spectroscopy (MRS) have demonstrated the presence of disease foci outside of the MRI defined volumes. This case highlights such a finding, wherein there was a detection of metabolically active focus of disease outside of the MRI-defined edema. The incorporation of metabolic imaging with MRI into the radiation treatment planning (RTP) process for HGG may be crucial in order to realize an adequate coverage of all disease burden, while at the same time guiding the delivery of ablative doses of radiation boost to foci of hyper-avidities.


 > Case Report Top


A gentleman of 54-year-old had been complaining of unexplained headaches for a span of 6 months, following which there was a sudden history of altered sensorium. He was subsequently diagnosed as suffering from a high-grade glioma (HGG) and was declared inoperable by virtue of the tumor location and volume. He was thus referred to us for palliative chemoradiotherapy.

In addition to MRI, a 11 C-MET-PET/CT was also procured for the purpose of RT planning. The areas of avidity as highlighted upon in the MET-PET were not totally concordant with areas depicted on the MRI. Given that methionine-uptake is considered negligible in the brain parenchyma, any avidity noted in the brain could be considered significant. There was a focus of avidity which extended beyond the T2-FLAIR edema [Figure 1]. It can further be noted that even within the areas depicted by the T1-Gd, certain foci had higher avidity in comparison to the rest, possibly denoting intratumoral heterogeneity [Figure 2].
Figure 1: Demonstration of 11C-Methionine-PET defined area (green outline), the additional area of PET-avidity (red dotted outline) which extends beyond MRI defined edema (aqua outline). It is reasonable to state that the nonuse of PET (a) would have led to nonrecognition on MRI (b) of the red outlined area beyond the edema

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Figure 2:(a) Comparison of 11C-Methionine-PET/CT and (b) T1-Gd-contrast enhanced MRI. Note that the PET defined area (green outline superimposed over MRI) is larger in area than the enhancing areas on T1-Gd. Also to be noted is the observation of the PET-avidity being variable within the T1-Gd enhancing areas. Areas with avidity exceeding thrice that of the normal brain are outlined (dark blue outline), and the same outlines are superimposed over T1-Gd enhancing areas

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The patient under current discussion has been treated with a palliative intent, given the large volume inoperable tumor. However, we present this case with an intention to illustrate the potential for additional information which can be gained with the integration of MET-PET into the RTP process. Further, given that the patient has not undergone either of surgery or biopsy, the argument of 'tumor cell being seeded during surgery' as the cause for avidity beyond T2-determined edema can be ruled out.


 > Discussion Top


The emergence of MRI and the demonstration that MRI determined peritumoral edema contains microscopic disease have revolutionized the target delineation for RT among patients with HGG. Nevertheless, it must be acknowledged that despite the use of concurrent temozolamide and intensity modulated radiotherapy (IMRT), even after a gross total resection, the current survival outcomes among patients with HGG remains dismal.

Given that about 80% of post-RT HGG recurrences are 'central', that is, within the volume of prior full dose irradiation, various trials were attempted in the previous decades to attempt dose escalation as a means of reducing 'central recurrences'. However, these trials failed to provide any significant benefit. It must be noted that dose escalation trials conducted in the previous decades had their drawbacks, such as the lack of MRI-based planning, the lack of temozolamide, the lack of conformal RT, and also that they utilized approaches such as hyper-fractionation, the rationale of which remains questionable. [1]

In the modern era, doses up to 60 Gray (Gy) are routinely achievable with the use of IMRT. However, given that further dose escalation to the entire T1-Gd volume would be hazardous, the use of modalities such as PET and MRS have been attempted to define smaller volumes which are more amenable to be boosted to higher doses, often with the use of stereotactic hypofractionated techniques and particulate radiotherapy.

The use of 11 C-methionine (a radiolabelled amino acid) with PET provides an opportunity to visualize the patterns of infiltration of gliomas, which may often not concur with MRI defined edema. [2] MET-PET seems to have a higher sensitivity and specificity in comparison to MRI. [3] Areas with MET-uptake are more often than not, larger than areas defined by T1-Gd. The provision of 20 mm margin around T2-FLAIR and T1-Gd, is estimated to cover only 96.4 and 86.4% of the areas with MET-uptake, respectively. [4] It has also been observed that MET-uptake does not exactly compare with T2-defined areas either, with isolated observations been made of MET-uptake exceeding to beyond 40 mm beyond T2-defined edema. [3] Pre-RT MET-PET has also been shown to be predictive of areas of high risk of recurrence. [5]

Various investigators have conducted small studies to integrate metabolic information from 11 C-MET-PET and MRS with the RTP process. Most studies do not use PET/MRS as a substitute for MRI, but in fact regard the different modalities as complimentary. Maximum interest has been towards the identification of areas with maximum risk of relapse, so as to plan boost doses to small volumes. [5],[6],[7]]

The most recent dose escalation studies have attempted dose escalation to as high as >90 Gy equivalents to metabolically defined volumes. Though survival benefits have often been reported, given the small design of these studies, significant conclusions cannot be made at this instance. However, with dose escalation beyond 70-80 Gy, there exists a change in the trend of patterns of failure, which seem to occur more often as marginal and distant, rather than 'central', which is otherwise seen with conventional doses. Further, with the use of modern techniques for boosting small volumes beyond 66 Gy, the risk of grade three-fourth toxicities do not seem to be larger than those seen with lower doses. [8],[9],[10]

While focal dose escalation using metabolic imaging may hold the potential to reduce the risk of central recurrences, the use of PET/MRS to define areas of activity beyond T2-determined 'edema' may hold promise in preventing, to an extent, the marginal and distant relapses. This is of importance, given that gliomas are infiltrative in nature, and may microscopically infiltrate to areas not visualized as the T2-defined 'edema'.

It is likely that advances in imaging for microscopic disease, when combined with modern conformal RT and particulate RT may help attain meaningful survival rates among patients with high-grade gliomas.

 
 > References Top

1.Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, et al. [ 18 F] Fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma. Radiat Oncol 2008;3:44.  Back to cited text no. 1
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2.Götz L, Spehl TS, Weber WA, Grosu AL. PET and SPECT for radiation treatment planning. Q J Nucl Med Mol Imaging 2012;56:163-72.  Back to cited text no. 2
    
3.Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol 2010;96:325-7.  Back to cited text no. 3
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4.Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, et al. Impact of [ 11 C] methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys 2012;82:83-9.  Back to cited text no. 4
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5.Lee IH, Piert M, Gomez-Hassan D, Junck L, Rogers L, Hayman J, et al. Association of 11 C-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.  Back to cited text no. 5
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6.Laprie A, Catalaa I, Cassol E, McKnight TR, Berchery D, Marre D, et al. Proton magnetic resonance spectroscopic imaging in newly diagnosed glioblastoma: Predictive value for the site of postradiotherapy relapse in a prospective longitudinal study. Int J Radiat Oncol Biol Phys 2008;70:773-81.  Back to cited text no. 6
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7.Pirzkall A, McKnight TR, Graves EE, Carol MP, Sneed PK, Wara WW, et al. MR-spectroscopy guided target delineation for high-grade gliomas. Int J Radiat Oncol Biol Phys 2001;50:915-28.  Back to cited text no. 7
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8.Miwa K, Matsuo M, Shinoda J, Oka N, Kato T, Okumura A, et al. Simultaneous integrated boost technique by helical tomotherapy for the treatment of glioblastoma multiforme with 11 C-methionine PET: Report of three cases. J Neurooncol 2008;87:333-9.  Back to cited text no. 8
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9.Fitzek MM, Thornton AF, Rabinov JD, Lev MH, Pardo FS, Munzenrider JE, et al. Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: Results of a phase II prospective trial. J Neurosurg 1999;91:251-60.  Back to cited text no. 9
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10.Chung CH, Parker J, Levy S, Slebos RJ, Dicker AP, Rodeck U. Gene expression profiles as markers of aggressive disease-EGFR as a factor. Int J Radiat Oncol Biol Phys 2007;69:S102-5.  Back to cited text no. 10
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