Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis
Open Access
- 27 April 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (4), e35711
- https://doi.org/10.1371/journal.pone.0035711
Abstract
Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease. We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors. WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of café-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10). WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations.Keywords
This publication has 41 references indexed in Scilit:
- Mortality in neurofibromatosis 1: in North West England: an assessment of actuarial survival in a region of the UK since 1989European Journal of Human Genetics, 2011
- Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in FranceOrphanet Journal of Rare Diseases, 2011
- Merlin/NF2 Suppresses Tumorigenesis by Inhibiting the E3 Ubiquitin Ligase CRL4DCAF1 in the NucleusCell, 2010
- Nf1-Dependent Tumors Require a Microenvironment Containing Nf1+/−- and c-kit-Dependent Bone MarrowCell, 2008
- Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1Neuro-Oncology, 2008
- Nf2/Merlin: a coordinator of receptor signalling and intercellular contactBritish Journal of Cancer, 2007
- Germline Mutation of INI1/SMARCB1 in Familial SchwannomatosisAmerican Journal of Human Genetics, 2007
- An Absence of Cutaneous Neurofibromas Associated with a 3-bp Inframe Deletion in Exon 17 of the NF1 Gene (c.2970-2972 delAAT): Evidence of a Clinically Significant NF1 Genotype-Phenotype CorrelationAmerican Journal of Human Genetics, 2007
- Genotype-Phenotype Correlations for Nervous System Tumors in Neurofibromatosis 2: A Population-Based StudyAmerican Journal of Human Genetics, 2004
- The Small-Sample Bias of the Gini Coefficient: Results and Implications for Empirical ResearchThe Review of Economics and Statistics, 2003