¹⁸F-FDG PET/CT Qualitative and Quantitative Evaluation in Neurofibromatosis Type 1 Patients for Detection of Malignant Transformation: Comparison of Early to Delayed Imaging With and Without Liver Activity Normalization

Abstract

18 F-FDG PET/CT has shown increased accuracy, compared with morphologic imaging, in differentiating malignant peripheral nerve sheath tumors (MPNSTs) from benign neurofibromas (BNFs) in patients with neurofibromatosis type 1 (NF1). Delayed 18 F-FDG PET imaging typically enhances malignant tumor to background. Our goal was to compare the effectiveness of early (1-h) and delayed (4-h) 18 F-FDG PET/CT imaging in differentiating MPNSTs from BNFs in patients with NF1, with and without liver activity normalization. Methods: NF1 patients presenting new symptoms or enlarging lesions were clinically evaluated with early and delayed 18 F-FDG PET/CT imaging. SUL max (maximum standardized uptake value derived for lean body) and SUL max/liver (lesion uptake adjusted to mean liver activity) were obtained for all sites identified with abnormal metabolic activity. Qualitative and quantitative evaluations, including receiver-operating-characteristic (ROC) comparison of early and delayed imaging sessions, were performed. Histopathology and clinical follow-up (1-9 y) were considered as a gold standard. Results: Forty-one NF1 patients with early and delayed 18 F-FDG PET/CT scans were identified, and 93 lesions were retrospectively analyzed, representing 24 MPNSTs (all histologically confirmed) and 69 BNFs (26 histologically confirmed). Qualitative evaluation on early imaging showed sensitivity, specificity, positive predictive value, and negative predictive value for separating MPNSTs from BNFs of 91%, 84%, 67%, and 96% versus 91%, 81%, 63%, and 96%, respectively, on 4-h delayed imaging. The mean SUL max was significantly higher for MPNSTs than BNFs on both early scans (6.5 vs. 2.0, P , 0.01) and delayed imaging (8.3 vs. 2.3, P , 0.02). However, SUL max overlap between benign and malignant lesions persisted even after normalization to mean liver activity. ROC-derived best SUL max cutoffs were 3.2 on early (area under the curve, 0.973) and 4.1 on delayed scans (area under the curve, 0.978). ROC analysis for SUL max/liver improved test specificity (94% vs. 87%, P , 0.05) on early and (93% vs. 88%, P , 0.05) on delayed imaging. Conclusion: Qualitative interpretation of 18 F-FDG PET/CT discriminates MPNSTs from BNFs in NF1 patients with similar accuracy on both early and delayed imaging. Quantitative data showed better sensitivity on delayed acquisition and best test specificity with lesion SUL max normalization to liver activity, more so than with delayed imaging at 4 h.

Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1–associated, and radiation-associated malignant peripheral nerve sheath tumors

“…Large index tumor size was implicated as a major adverse prognostic factor which recapitulates the importance of early diagnosis and intervention in these aggressive tumors, particularly in the NF1 population where 18F-FDG PET/CT has been shown to appropriately discriminate between benign peripheral nerve sheath tumors and MPNSTs. 5 Finally, differences in clinicopathologic features and patterns of local recurrence and survival do exist between sporadic, NF1-asssociated, and RT-associated MPNST; therefore, the etiology of these tumors should be considered in the management of these patients and in future studies evaluating their biology.…”

The Role of [18F]FDG-PET/CT in Predicting Malignant Transformation of Plexiform Neurofibromas in Neurofibromatosis-1

“…ROC analysis was performed in selected studies for optimum SUV max cut-off [12, 13, 16, 18, 19]. These values yielded cut-offs of 3.1, 3.2, 3.5, 4.1, and 6.1 to achieve maximum sensitivity and specificity of identifying malignant lesions.…”

Dual-time-point Imaging and Delayed-time-point Fluorodeoxyglucose-PET/Computed Tomography Imaging in Various Clinical Settings

“…2). 30 The impact of this imaging technique on diagnosis, prognosis, 31 and treatment planning 32 has been assessed for different malignant and benign diseases, 33 and the benefits and pitfalls of DTPI are shown in Table 2.…”