Poster sessions are an opportunity for researchers to showcase their work in Basic and Clinical Sciences to an audience of NF researchers. A panel of judges select the top posters, and these investigators are invited to present their work in front of the full conference.
Below are the top posters at the 2022 NF Conference in Clinical and Basic Sciences.
CLINICAL SCIENCE
1) Inka Ristow, MD – University Medical Center Hamburg – Eppendorf, Germany
“Characterization of benign, atypical and malignant peripheral nerve sheath tumors in patients with Neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging”
2) Taylor Sundby, MD – National Cancer Institute
“Machine Learning Integration of Multimodal cell free DNA features enhances detection of peripheral nerve sheath tumors”
3) Madeleine Franchi, MS – University of Alabama at Birmingham
“Parents’ Perspectives of Disclosing a Pediatric Diagnosis of Neurofibromatosis Type 1 to their Children”
BASIC SCIENCE
1) (tie) Miriam Mansour, PhD Student – Institute Mondor de Rechcherche Medicale
“Exploring mechanisms governing initiation and progression of plexiform neurofibromas using Prss56Cre, Nf1/fl/fl mouse model”
1) (tie) Catena Kresbach, MD – University Medical Center of Hamburg
“Molecular and clinical refinement of atypical neurofibroma”
3) Krizelle Alcantara, MS – Nationwide Children’s Hospital
“In vitro Modeling of Neurofibromatosis type 2 (NF2) to Explore Potential Therapies in the Context of Patient-Specific Mutations”
CLINICAL SCIENCE
1) Inka Ristow, MD – University Medical Center Hamburg – Eppendorf, Germany
“Characterization of benign, atypical and malignant peripheral nerve sheath tumors in patients with Neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging”
NF1 is associated with development of benign and malignant (MPNST) peripheral nerve sheath tmors. Newly described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Diffusion-weighted imaging (DWI) is an established magnetic resonance imaging (MRI) method to distinguish BPNSTs from MPNSTs in NF1 patients. The aim of this study was to evaluate the value of DW-MRI in distinguishing pre-malignant ANFs from BPNSSTs and MPNSTs using the apparent diffusion coefficient (ADC).
In the single center study, DW-MRI provides additional quantitative information to differentiate not only malignant but also pre-malignant tumors from benign tumors in NF1 patients both of which require surgical resection. Application of DW-MRI might hence reduce invasive diagnostic procedures.
2) Taylor Sundby, MD – National Cancer Institute
“Machine Learning Integration of Multimodal cell free DNA features enhances detection of peripheral nerve sheath tumors”
Early detection of transformation of plexiform neurofibroma (PN) to atypical neurofibroma (AN) and malignant peripheral nerve sheath tumors (MPNST) remains challenging with standard of care imaging and tissue biopsies, largely due to tissue heterogeneity. We previously demonstrated that cell-free DNA (cfDNA) accurately and non-invasively distinguishes MPNST from PN using global copy number alteration (CNA) analysis. Our published assay, however, had limited sensitivity for relatively genomically-stable disease-states; leave-one-out cross-validation (LOOCV) accuracy for PN vs healthy was 56%. Genomic instability increases as peripheral nerve sheath tumors (PNST) transform, with PN (median 9 CNA/tumor) and AN (median 23 CNA/tumor) demonstrating relative stability relative to MPNST (median 428 CNA/tumor). Improving accurate cfDNA detection of genomically-stable PNST has the potential to improve early detection of clinically relevant pre-malignant and early-stage malignant tumors.
Inclusion of regional genomic characteristics and fragmentomics in cfDNA classification algorithms improved accuracies for all peripheral nerve sheath tumor states, most strikingly PN from healthy controls. Accurate classification of relatively genomically-stable PN hold promise for application of this framework to (a) detect low-mutational burden AN, (b) detect early MPNST with low circulating variant allele fractions, and (c) cfDNA based monitoring of PN burden.
3) Madeleine Franchi, MS – University of Alabama at Birmingham
“Parents’ Perspectives of Disclosing a Pediatric Diagnosis of Neurofibromatosis Type 1 to their Children”
Neurofibromatosis 1 (NF1) is a common genetic disorder typically diagnosed in childhood and characterized by cutaneous findings, nerve sheath tumors, skeletal abnormalities, malignancies, and developmental differences. Due to its variability, NF1 is an unpredictable condition that parents have concerns about discussing with their children. While there are publications addressing disclosure of genetic conditions in general, no NF1 specific disclosure literature exists. To fill this gap, this mixed methods study sought to evaluate the concerns, barriers, failures, or successes parents or guardians have experienced when they have or have not chosen to tell their child(ren) about an NF1 diagnosis.
Results indicated that most parents (70.5%) disclosed the NF1 diagnosis to their child and overall felt it was a positive experience. Almost one-third of parents (29.5%) had not disclosed the diagnosis. A strong significance was identified between disclosure and severe presentation of NF1 (p=0.0008). Parents in both groups shared similar concerns about discussing the diagnosis due to its complexity and multiple factors influenced the disclosure decision. Most parents approached disclosure as a process and emphasized the need to be honest and support their child throughout the process. Parents highlighted the need for more educational resources for children and guidance on how to disclose the diagnosis. These findings indicate that additional resources and support for parents would facilitate disclosure and the involvement of healthcare providers in the process would be beneficial.
BASIC SCIENCE
1) (tie) Miriam Mansour, PhD Student – Institute Mondor de Rechcherche Medicale
“Exploring mechanisms governing initiation and progression of plexiform neurofibromas using Prss56Cre, Nf1/fl/fl mouse model”
Patients with Neurofibromatosis type 1 (NF1) develop benign nerve sheath tumors called plexiform neurofibromas (pNFs). PNFs are among the most common and debilitating complications of NF1. Interestingly, development of pNFs is preceded by the local nerve enlargement called hyperplasia. The goal of the study is to characterize hyperplastic nerves (HNs) and to identify mechanisms and molecules governing their progression into pNFs.
Their laboratory has developed a novel genetically engineered Nf1-KO mouse model that successfully recapitulates development of HNs that progress into pNFs. Interestingly, while in this model, pNFs develop spontaneously in adult mice, their development is significantly faster in mutant mice of the same age with skin trauma, pointing to inflammation as an important trigger.
It is firmly established that around 50% of the volume of pNFs corresponds to collagen produced by fibroblasts from the nerve microenvironment. Red Sirius staining (marker of collagen) of HNs reveal that fibrosis is already present at that stage suggesting implication of tumor SC in fibrosis.
2) (tie) Catena Kresbach, MD – University Medical Center of Hamburg
“Molecular and clinical refinement of atypical neurofibroma”
Atypical neurofibroma (ANF) are believed to be at risk for progression to highly aggressive malignant peripheral nerve sheath tumors (MPNST). Therefore, the identification of such lesions is of high importance for risk adapted patient care and could help to reduce the mortality of NF1 patients. Based on small series, different histological and imaging criteria have been proposed to identify “atypical neurofibroma” (ANF) or “atypical neurofibromatous neoplasms of uncertain biological potential” (ANNUBPs), but a satisfying consensus definition has not yet been reached. Most importantly, a thorough molecular and clinical characterization is missing to date. The aim of this study is to identify robust diagnostic markers for atypical neurofibroma and indicators for lesions at risk for malignant transformation.
While histological identification of ANF is challenging and rater-dependent, our results indicate that global DNA methylation analysis can provide a promising tool to unambiguously distinguish NF with differing extend of histopathological atypia from bland NF and MPNST. Further molecular workup including NGS as well as clinical characterization of affected patients are ongoing and will contribute new insight into ANF that allows standardized identification and risk interpretation of ANF in order to improve patient care.
3) Krizelle Alcantara, MS – Nationwide Children’s Hospital
“In vitro Modeling of Neurofibromatosis type 2 (NF2) to Explore Potential Therapies in the Context of Patient-Specific Mutations”
Neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome characterized by nervous system tumors, primarily schwannomas, meningiomas, and ependymomas, which originate from loss of heterogeneity (LOH) in the NF2 gene. Current treatment options for NF2 are limited to surgery and radiotherapy, but these are often invasive and may lead to further nerve damage and secondary malignancies. Moreover, due to the underlying genetic contributions to tumor formation, successful treatments are short-lived and inadequate as more tumors may develop in previously unaffected cells.
Phenotypic heterogeneity in NF2 ranges from benign to severe clinical presentation, but genetic analysis does not always correlate with disease symptoms. This broad clinical phenotype of patients makes it difficult to develop therapies for halting disease progression as it is currently unclear if variations in NF2 mutations will have a differential response to therapy. Thus, we have developed a human NF2 in vitro model to gain understanding of the broad-spectrum mutations leading to disease and to evaluate potential therapies.
These new in vitro tools allow studying disease mechanisms in the context of patient mutations. In addition, we are currently testing several therapeutic approaches for NF2 including adeno-associated virus (AAV)-based gene replacement therapy for rescuing NF2 expression and small molecule drug treatment for inhibiting tumor progression. Our preliminary results show that this model system allows simultaneous evaluation of gene therapy and complementary combination approaches in a highly variable patient population.
