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

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

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   > 3.5 Ferner et al. J Neurol Neurosurg Psychiatry 2000;68: Bredella et al.AJR 2007;189: Ferner et al. Ann Oncol 2008; 19(2):390-4

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

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

Benign Early Imaging Late Imaging

Malignant (1) Early Imaging Late Imaging

Malignant (2) Early Imaging Late Imaging

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)

Results (2)  On the basis of semi-quantitative analysis PET/CT classified:  43 malignant  42 benign Type of TumourNegative on 18 FDG PET/CT Positive on 18 FDG PET/CT Neurofibroma26 Atypical19 Low Grade011 High Grade010 Sensitivity 0.97 (95% CI ) Specificity 0.87 (95% CI )

Results (3) - SUVmax Comparsion Mean SUVmax Benign Lesions on PET Malignant Lesions on PET Early2.0 (CI ) 7.0 (CI ) Late1.9 (CI ) 8.1 (CI ) 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= ) SUVmax early vs. delayed imaging for tumours classified as malignant on PET/CT (p=0.0005)

Results (4) - Histology vs SUVmax Mean SUVmax AtypicalLow GradeHigh Grade Early Late 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)

Results (5) - Histology vs SUVmax

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