Recommendations for assessing appearance concerns related to plexiform and cutaneous neurofibromas in neurofibromatosis 1 clinical trials.

BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.

Parent perspectives on disclosing a pediatric neurofibromatosis type 1 diagnosis.

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 the 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. Parents of children between ages 0 and 17 with a diagnosis of NF1 completed a survey and some parents were selected for an interview invitation. A total of 258 surveys were completed, and 20 parents were interviewed. Interview transcripts were categorized into disclosure and non-disclosure groups. Themes were organized into five categories based on interview questions: disclosure concerns, factors affecting disclosure/non-disclosure, approaches to disclosure, desired resources, and recommendations for disclosure. Sentiment analysis was performed on responses about the disclosure discussion itself. 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 and multiple factors influenced the disclosure decision. Most parents approached disclosure as a process and emphasized the need to be honest and supportive of their child. Parents highlighted the need for more educational resources for children and guidance on how to disclose. These findings indicate that additional resources and support for parents would facilitate disclosure and the involvement of genetic counselors in the process would be beneficial.

Does genetic testing offer utility as a supplement to traditional family health history intake for inherited disease risk?

CONTENT: This study examines the potential utility of genetic testing as a supplement to family health history to screen for increased risk of inherited disease. Medical conditions are often misreported or misunderstood, especially those related to different forms of cardiac disease (arrhythmias vs. structural heart disease vs. coronary artery disease), female organ cancers (uterine vs. ovarian vs. cervical), and type of cancer (differentiating primary cancer from metastases to other organs). While these nuances appear subtle, they can dramatically alter medical management. For example, different types of cardiac failure (structural, arrhythmia, and coronary artery disease) have inherited forms that are managed with vastly different approaches. METHODS: Using a dataset of over 6,200 individuals who underwent genetic screening, we compared the ability of genetic testing and traditional family health history to identify increased risk of inherited disease. A further, in-depth qualitative study of individuals for whom risk identified through each method was discordant, explored whether this discordance could be addressed through changes in family health history intake. FINDINGS: Of 90 individuals for whom genetic testing indicated significant increased risk for inherited disease, two-thirds (66%) had no corroborating family health history. Specifically, we identify cardiomyopathy, arrhythmia, and malignant hyperthermia as conditions for which discordance between genetic testing and traditional family health history was greatest, and familial hypercholesterolaemia, Lynch syndrome, and hereditary breast and ovarian cancer as conditions for which greater concordance existed. CONCLUSION: We conclude that genetic testing offers utility as a supplement to traditional family health history intake over certain conditions.

Enhancing Neurofibromatosis Clinical Trial Outcome Measures Through Patient Engagement: Lessons From REiNS.

OBJECTIVE: As part of an evaluation of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration patient representative program, we surveyed REiNS members to (1) identify facilitators and barriers to involving patient representatives and (2) understand whether and how involving patient representatives affected recommendations for clinical trial outcomes. METHODS: We administered an anonymous online survey to all REiNS members. Facilitators and barriers to patient representative involvement were solicited using a modified free listing technique; responses were inductively grouped into higher-order categories and ranked based on saliency score (Smith s). Open-ended questions assessed patient representative expectations for engagement, perceived benefits/costs of patient engagement, and patient representative contributions; responses were analyzed using conventional content analysis. RESULTS: A total of 63/172 (37%) members responded, including 18/30 (60%) patient representatives. Providing sufficient opportunities to meaningfully engage in research tasks and cultivating a respectful, inclusive atmosphere were key facilitators to patient representatives' satisfaction and ability to make an impact. Respondents perceived that patient representatives directly (through their input on research tasks) and indirectly (through effects on other stakeholders' knowledge and communication style) improved the organization's research, leading to selection of more meaningful, relevant, and feasible clinical trial outcome measures. Ongoing challenges to patient engagement include difficulty scheduling meetings and concerns about the level of scientific knowledge patient representatives needed to effectively engage. CONCLUSIONS: Involving patient representatives in REiNS improved perceived quality of neurofibromatosis clinical trial outcome measures. Negotiating sufficient opportunities to engage, fostering an inclusive atmosphere, and navigating time pressures are key to effective patient engagement.