title: Metabolic Tumour Burden Measured by 18F-FDG PET/CT Predicts Malignant Transformation in Patients with Neurofibromatosis Type-1.
abstract: BACKGROUND
  To investigate the diagnostic and prognostic performances of 18F-FDG PET/CT measures of metabolic tumour burden in patients with neurofibromatosis type-1 (NF1), suspect of malignant transformation.
  
  
  METHODS
  This retrospective study included 49 patients (15-60 years old, 30 women) with a diagnosis of NF1, followed in our Reference Centre for Rare Neuromuscular Diseases, who presented clinical signs of tumour progression (pain, neurological deficit, tumour growth). Quantitative metabolic parameters were measured on 149 tumoral targets, using semi-automatic software and the best cut off values to predict transformation was assessed by Receiver Operating Characteristics (ROC) analysis. Prognostic value of PET/CT metabolic parameters was assessed by Kaplan-Meier estimates of overall survival.
  
  
  RESULTS
  Lesions were histologically documented in 40 patients: a sarcomatous transformation was found in 16, a dysplastic neurofibroma (NF) in 7, and a benign NF in 17; in the remaining 9 patients, a minimal follow-up of 12 mo (median 59 mo) confirmed the absence of transformation. The optimal cut off values for detection of malignant transformation were, in decreasing order of area under the ROC curves, a tumour-to-liver (T/L) ratio >2.5, SUVmax > 4.5, total lesion glycolysis (TLG) > 377, total metabolic tumour volume (TMTV) > 88 cm3, and heterogeneity index (HIsuv) > 1.69. The best prognostic marker was the TLG: the 4-y estimates of survival were 97% [95% CI, 90% - 100%] in patients with TLG ≤ 377 vs. 27% [95% CI, 5% - 49%] in patients with TLG > 377 (P < 0.0001; χ2 27.85; hazard ratio 13.27 [95% CI, 3.72-47.35]). T/L ratio, SUVmax and TMTV demonstrated slightly lower performance to predict survival, with χ2 ranging 14.41-19.12. The HIsuv index was not predictive of survival.
  
  
  CONCLUSIONS
  Our study demonstrates that TLG and TMTV, as PET/CT measures of metabolic tumour burden, may be used clinically to identify sarcomatous transformation in patients with NF1 and predict overall survival, with a higher specificity for the TLG. Conventional measures such as the SUVmax, and T/L ratio also demonstrate high prognostic value.
authors.affiliation: Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Axel
authors.initials: A
authors.lastname: Van Der Gucht
authors.affiliation: Department of Dermatology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Ouidad
authors.initials: O
authors.lastname: Zehou
authors.affiliation: Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Soraya
authors.initials: S
authors.lastname: Djelbani-Ahmed
authors.affiliation: Department of Dermatology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
authors.affiliation: Department of Pathology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.affiliation: Department of Neuroradiology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Pierre
authors.initials: P
authors.lastname: Brugières
authors.affiliation: Department of Dermatology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.affiliation: Department of Medical Imaging, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Alain
authors.initials: A
authors.lastname: Luciani
authors.affiliation: Department of Medical Imaging, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Alain
authors.initials: A
authors.lastname: Rahmouni
authors.affiliation: Department of Dermatology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Emilie
authors.initials: E
authors.lastname: Sbidian
authors.affiliation: Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Itti
mesh_terms: D000293:Adolescent; D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18