Pet and gbm

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Evidence-Based Surgery:

Positron-Emission Tomography (PET) for diagnosis of recurrence in gliomas

Johnny Wong

14th April, 2011

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Case: LB

• 45 year old woman

• Presented with dysphasia

• Craniotomy and excision of tumour (09/10)

• Histology: Anaplastic Astrocytoma (WHO III)

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• Post-op dysphasia & dysarthria gradually resolved

• CATNON trial – XRT only

• Significantly worsening dysphasia

• MRI & FDG-PET in 01/11

• Tumour recurrence or radiation necrosis?

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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 ?

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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

Results of search: • 17 articles• 10 useful

articles• 1 related• 3 not

accessible• 3 not

relevant

Results of search: 65 articles, 3 additional articles

3 more articles

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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)

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Positron-emission tomography (PET):

• Glucose – F18-FDG

– Correlation between grade and glucose metabolism

– Difficulty with low-grade lesions

– High baseline in normal cerebral cortex

– Sensitivity: 40-86%

– Specificity: 22-100%

• Amino-acids– AA transport and protein

synthesis; also in inflammatory cells

– MET: Methionine (Short half-life)

– FET: tyrosine

– FLT: thymidine

– N-NH3: Ammonia

– FFCho: Choline (membrane synthesis)

– IMT-SPECT

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“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%

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“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%

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“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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“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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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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Multi-voxel MRS

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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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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.

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Latest follow-up

• Commenced on Avastin (Bevacizumab) and Temodal (Temozolomide)

• Good improvement clincially and radiologically

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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, 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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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.