18 FDG PET/CT in the diagnosis of Malignant Peripheral Nerve Sheath Tumours

1. 18 FDG PET/CT in the diagnosis of Malignant Peripheral Nerve Sheath Tumours VS Warbey, RE Ferner, JT Dunn, E Calonje, MJ O’Doherty St Thomas’ Clinical PET Centre and Department of Clinical Neurosciences Guy’s, King’s and St Thomas’ School of Medicine

2. Introduction • MPNST in NF1 – a diagnostic challenge • Overlap of clinical manifestations • MRI identifies site and extent, not reliable in detecting malignant change • Histology is the final arbiter of malignancy • Management requires a Specialist MDM approach

3. Background • Previous work by our group and others has concluded that 18FDG-PET is helpful in determining malignant change in neurofibromas • Significant difference in SUVmax between benign and malignant lesions with delayed imaging at approximately 200 minutes • SUVmax on delayed imaging • < 2.5 • 2.5 - 3.5 • > 3.5 Ferner et al. J Neurol Neurosurg Psychiatry 2000;68:353-357 Bredella et al.AJR 2007;189:928-935 Ferner et al. Ann Oncol 2008; 19(2):390-4

4. Aims • To evaluate the sensitivity of PET/CT • To clarify the value of early and delayed imaging • To re-validate the current cut-off values for identification of malignant change within neurofibromas using PET/CT • To examine the relationship between SUV and tumour grade

5. Methods • Patients with symptomatic neurofibromas referred for 18FDG PET/CT were identified from the reports archive • Early and delayed imaging (90 minutes, 4 hours) • SUVmax measured • Classified as malignant: • SUVmax rose to > 3.5 on delayed imaging • Histological correlation

6. Early Imaging Late Imaging Benign

7. Malignant (1) Early Imaging Late Imaging

8. Malignant (2) Early Imaging Late Imaging

9. Results (1) • 97 studies were identified from the PET/CT reports archive over a 35-month period from August 2004 to April 2008 • Final analysis: 69 studies in 62 patients, 85 neurofibromas • Exclusions: No delayed imaging/no focal uptake, alternative diagnosis, repeat lesion • 31 males, 31 females • Mean age 31 years, age range 9 – 86 • Median imaging times • Early 101 minutes (1 hour 41 minutes) • Late 252 minutes (4 hours 12 minutes)

10. Results (2) • On the basis of semi-quantitative analysis PET/CT classified: • 43 malignant • 42 benign Sensitivity 0.97 (95% CI 0.81-0.99) Specificity 0.87 (95% CI 0.74-0.95)

11. Results (3) - SUVmax Comparsion Early vs. delayed imaging ([type irrelevant] F­1,83 = 9.98, p=0.0022) Benign vs. malignant ([time irrelevant] F­1,83 = 56.14, p<<0.0001) Significant interaction effect between time and tumour type (F­1,83 = 14.72, p=0.00017) SUVmax early vs. delayed imaging for tumours classified as malignant on PET/CT (p=0.0005)

12. Results (4) - Histology vs SUVmax SUVmax between tumour types ([time irrelevant] F2,27 = 7.91, p=0.002) SUVmax early vs. delayed imaging (F1,27= 10.58, p=0.003)

13. Results (5) - Histology vs SUVmax

14. Conclusions • Recommend early and delayed PET/CT imaging for accurate lesion characterisation • Continue to recommend a cut-off value SUVmaxD=3.5 • Acceptable to maintain a high sensitivity at expense of false positive studies • First study that has demonstrated a correlation between SUVmax and tumour grade