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Evidence-Based Surgery:Positron-Emission Tomography (PET)for diagnosis of recurrence in gliomas                Johnny Wong...
Case: LB• 45 year old woman• Presented with  dysphasia• Craniotomy and  excision of tumour  (09/10)• Histology: Anaplastic...
• Post-op dysphasia &  dysarthria gradually  resolved• CATNON trial – XRT  only• Significantly  worsening dysphasia• MRI &...
Clinical Questions:• What is the sensitivity and specificity of PET in  diagnosing tumour recurrence in high-grade  astroc...
Search strategy•   P = Patients with high-grade astrocytoma•   I = Positron-emission tomography•   C = Magnetic resonance ...
Results ofsearch:• 17 articles• 10 usefularticles• 1 related• 3 notaccessible• 3 notrelevant
Results of search: 65 articles, 3 additional articles
3 morearticles
Effects of XRT and chemotherapy• Radiotherapy  – Pseudo-progression (Enhancement within 2 months XRT)  – Radiation necrosi...
Positron-emission tomography (PET):• Glucose                       • Amino-acids  – F18-FDG                       – AA tra...
“Sensitivity and specificity of PET”• FDG vs MET-PET (Van Laere 2005)  –   30 patients; both scans on same day.  –   Gliom...
“Sensitivity and specificity of PET”• FDG vs MET-PET: (Potzi et al.)   – 28 patients; Histologically confirmed GBM   – MRI...
“Sensitivity and specificity of PET”• FET vs MRI (Rachinger et al 2005)   – 45 patients (32 tissue diagnosis of recurrence...
“Sensitivity and specificity of PET”• FDG vs 13N-NH3 (Zhang et al, 2007)   – 8 patients, Gd enhanced lesions   – FDG and N...
Other modalities – MRS and DWI• MRI + Gad: Not suitable for diagnosis of  recurrence, especially after anti-VEGF (Sens and...
Multi-voxel MRS                  17
The “gold standard” for diagnosis ofrecurrence:• MRI   – Progression of enhancing lesion   – Heterogeneity of lesion grade...
Implications from PET• MET-PET vs Gad-enhancement (Galldiks et al. 2009)   –   12 patients; Histologically confirmed GBM  ...
20
Latest follow-up                   • Commenced on                     Avastin                     (Bevacizumab) and       ...
References1.   Yang I, Aghi M. New advances that enable identification of glioblastoma     recurrence. Nat. Rev. Clin Onco...
6.   Van Laere et al. Direct comparison of 18F-FDG and 11C-Methionine PET in     suspected recurrence of glioma: sensitivi...
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Pet and gbm

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  • Pseudo:Within 2 months of XRTMinimal abnormal histologySpontaneous resolutionRadiation nec3 – 12 months after XRT; Oedema and mass effect on MRINot always resolveEndothelial apoptosis, gliosis and White Matter necrosis
  • Highest tumour to background uptake: Fchol > FET > FDG. But all have increased uptake in inflammatory cells around necrosis.
  • Transcript of "Pet and gbm"

    1. 1. Evidence-Based Surgery:Positron-Emission Tomography (PET)for diagnosis of recurrence in gliomas Johnny Wong 14th April, 2011 1
    2. 2. Case: LB• 45 year old woman• Presented with dysphasia• Craniotomy and excision of tumour (09/10)• Histology: Anaplastic Astrocytoma (WHO III) 2
    3. 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. 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. 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. 6. Results ofsearch:• 17 articles• 10 usefularticles• 1 related• 3 notaccessible• 3 notrelevant
    7. 7. Results of search: 65 articles, 3 additional articles
    8. 8. 3 morearticles
    9. 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. 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 11
    11. 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. 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. 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) 14
    14. 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) 15
    15. 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) 16
    16. 16. Multi-voxel MRS 17
    17. 17. The “gold standard” for diagnosis ofrecurrence:• 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 18
    18. 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. 19. 20
    20. 20. Latest follow-up • Commenced on Avastin (Bevacizumab) and Temodal (Temozolomide) • Good improvement clincially and radiologically 21
    21. 21. References1. 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, 20073. 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, 20104. Zhang XS, Chen W. Differentiation of recurrent astrocytoma from radiation necrosis: a pilot study with 13N-NH3 Pet. J. Neurooncol 82:305-311, 20075. 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. 22
    22. 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, 20057. 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, 20048. 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. 23
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