1. Evidence-Based Surgery:
Positron-Emission Tomography (PET)
for diagnosis of recurrence in gliomas
Johnny Wong
14th April, 2011
1

2. Case: LB
• 45 year old woman
• Presented with
dysphasia
• Craniotomy and
excision of tumour
(09/10)
• Histology: Anaplastic
Astrocytoma (WHO III)
2

3. • Post-op dysphasia &
dysarthria gradually
resolved
• CATNON trial – XRT
only
• Significantly
worsening dysphasia
• MRI & FDG-PET in
01/11
• Tumour recurrence
or radiation
necrosis?
3

4. Clinical Questions:
• What is the sensitivity and specificity of PET in
diagnosing tumour recurrence in high-grade
astrocytomas ?
• What is the best imaging modality to differentiate
tumour recurrence from radionecrosis in
astrocytomas ?
4

5. Search strategy
• P = Patients with high-grade astrocytoma
• I = Positron-emission tomography
• C = Magnetic resonance imaging
• O = Sensitivity and specificity of diagnosing recurrence
and radiation necrosis
• Search terms (exp MESH and keywords): Astrocytoma,
GBM, Positron-emission tomography, recurrence,
radiation necrosis, “sensitivity and specificity”
– Limit to English and Humans
5

6. Results of
search:
• 17 articles
• 10 useful
articles
• 1 related
• 3 not
accessible
• 3 not
relevant

7. Results of search: 65 articles, 3 additional articles

8. 3 more
articles

9. Effects of XRT and chemotherapy
• Radiotherapy
– Pseudo-progression (Enhancement within 2 months XRT)
– Radiation necrosis (Enhancement after 3 – 12 months XRT)
– BBB breakdown / ↑ VEGF expression - ↑ permeability
• Chemotherapy
– Concommitant XRT and chemo – 3x more likely for
pseudoprogression
– Temozolamide sensitivity (MGMT –ve status) – increases
likelihood of pseudo-progression
– Avastin – anti-VEGF: increases sensitivity to XRT, decreased
permeability (less enhancement; increased FLAIR)
10

10. Positron-emission tomography (PET):
• Glucose • Amino-acids
– F18-FDG – AA transport and protein
– Correlation between synthesis; also in
grade and glucose inflammatory cells
metabolism
– Difficulty with low-grade – MET: Methionine (Short
lesions half-life)
– High baseline in normal – FET: tyrosine
cerebral cortex – FLT: thymidine
– Sensitivity: 40-86% – N-NH3: Ammonia
– Specificity: 22-100% – FFCho: Choline
(membrane synthesis)
– IMT-SPECT
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11. “Sensitivity and specificity of PET”
• FDG vs MET-PET (Van Laere 2005)
– 30 patients; both scans on same day.
– Gliomas (Grades II-IV astrocytomas, oligos and mixed)
– Radiology: recurrence 18/30, necrosis 4/30, unsure 5/30
– MET: Increased uptake: 28/30;
Inter-observer 100%; Sensitivity: 75%; Specificity: 70%; Accuracy: 73%
– FDG: Increased uptake: 17/30;
Inter-observer 73% ; Sensitivity: 95%, Specificity: 50%; Accuracy: 80%
12

12. “Sensitivity and specificity of PET”
• FDG vs MET-PET: (Potzi et al.)
– 28 patients; Histologically confirmed GBM
– MRI evidence of progression as “recurrence”
• MET-PET: Sens 89%, Spec 29%, Accuracy: 72%
• FDG: Sens 11%, Spec 100%, Accuracy: 36%
– Survival analysis for >12 months:
• MET-PET: Spec 8%, Accuracy 48%
• Other studies (Tsuyuguchi):
– Sens: 100%; Spec: 60%
– Accuracy:82%
13

13. “Sensitivity and specificity of PET”
• FET vs MRI (Rachinger et al 2005)
– 45 patients (32 tissue diagnosis of recurrence; 13 transient
symptoms)
– FET: half life 110 mins (vs MET 20 mins)
– FET-PET: Sensitivity 100%, specificity 92.9%
– MRI : Sensitivity 93.5%; specificity 50% (p<0.05)
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14. “Sensitivity and specificity of PET”
• FDG vs 13N-NH3 (Zhang et al, 2007)
– 8 patients, Gd enhanced lesions
– FDG and NH3
• NH3: 100% accuracy (6 recurrences, 2 necrosis)
• FDG: 75% accuracy (1 FP, 1 FN)
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15. Other modalities – MRS and DWI
• MRI + Gad: Not suitable for diagnosis of
recurrence, especially after anti-VEGF (Sens and
spec < 60%).
• DWI: ADC coefficient 1.82 vs 1.43 (P-P vs
recurrence, p<0.001)
• DTI: Radiation necrosis damages WM tracts vs
recurrences which displace them.
• MRS: 3-D multi-voxel MRS: 94% sensitivity; 100%
specificity (28 patients)
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16. Multi-voxel MRS
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17. The “gold standard” for diagnosis of
recurrence:
• MRI
– Progression of enhancing lesion
– Heterogeneity of lesion grades
• Stereotactic biopsy
– Sampling error
• Survival
– Confounding from different tumour grades and treatment
regimens
Larger studies required
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18. Implications from PET
• MET-PET vs Gad-enhancement (Galldiks et al. 2009)
– 12 patients; Histologically confirmed GBM
– Volumetric study
– MET uptake indices: >1.3 vs >1.5 and Gd-enhancement
– Active tumour volume: 30.17 vs 13.68 vs 13.7 cm3
– MET-PET detects larger tumour volume than the contrast
enhancement
• Implication for larger surgical resection margins.
– ? Higher reoperation rates because of higher
sensitivity and low specificity.
19

19. 20

20. Latest follow-up
• Commenced on
Avastin
(Bevacizumab) and
Temodal
(Temozolomide)
• Good improvement
clincially and
radiologically
21

21. References
1. Yang I, Aghi M. New advances that enable identification of glioblastoma
recurrence. Nat. Rev. Clin Oncol 6:648-657, 2009.
2. Potzi C, Becherer A, Marosi C et al. 11C Methionine and 18F
Fluorodeoxyglucose PET in the follow up of glioblastoma mutliforme. J.
Neurooncol 84:305-314, 2007
3. Galldiks N et al. Volumetry of 11C-Methionine PET uptake and MRI contrast
enhancement in patients with recurrent glioblastoma multiforme. Eur J Nucl
Med mol Imaging 37:84-92, 2010
4. Zhang XS, Chen W. Differentiation of recurrent astrocytoma from radiation
necrosis: a pilot study with 13N-NH3 Pet. J. Neurooncol 82:305-311, 2007
5. Rachinger W et al. Positron Emission tomography with O218F Fluroethyl L
tyrosine versus magnetic resonance imaging in the diagnosis of recurrent
gliomas. Neurosurg 57:505-511, 2005.
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22. 6. Van Laere et al. Direct comparison of 18F-FDG and 11C-Methionine PET in
suspected recurrence of glioma: sensitivity, interobserver variability and
prognostic value. Eur J. Nucl Med Mol Imaging 32:39-51, 2005
7. Tsuyuguchi et al. Methionine positron emission tomography for differentiation
of recurrent brain tumour and radiation necrosis after stereotactic radiosurgery
in malignant glioma. Annals Nucl Med 18:291-296, 2004
8. Mertens et al. PET with 18F-labelled choline based tracers for tumour imaging:
a review of the literature. Eur J. Nucl. Med Mol Imaging 37:2188-2193, 2010.
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