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REiNS Recommendations

This table provides a summary of all current REiNS consensus recommendations for neurofibromatosis and schwannomatosis clinical trials. The peer-reviewed REiNS publications that discuss each of these recommendations are linked from the table. There are also links to each of the recommended outcome measures and/or to the relevant subsections of each paper.

Clinical Trial Endpoint or Domain (full paper linked)

Recommended Primary Measure(s) or Key Points

Recommended Secondary/Exploratory Measure(s)


Clinical annotation

·    Minimal clinical dataset (Table 2)

·    Recommendations for sample collection and methodology

Cutaneous neurofibroma (cNF)

·    Recommended sample collection for cNF trials

·    Recommended annotation for cNF biopsy samples (Table 2)

Genotype-phenotype correlation

·    NF1—suggested that individuals with mutations p.Met992del and p.Arg1809Cys not be included in natural history studies or clinical trials investigating plexiform neurofibromas

·    NF2—genetic severity score

Functional Outcomes


·    Maximum word recognition score (WRS) (Table 2)

·    Pure-tone average (PTA)

Facial function

·    Scaled Measurement of Improvement in Lip Excursion (SMILE) analysis

Download FACEGRAM app (must be a member of the Sir Charles Bell Society)

·    House-Brackmann scale

Muscle strength

·    Handheld dynamometry (HHD) performed by a trained examiner using a well-defined protocol

Vision related to optic pathway gliomas

·    Visual acuity (VA) using Teller Acuity Cards (TAC)

·    HOTV testing once subjects are old enough to complete

·    Assess optic disc for pallor, as this may affect the interpretation of VA over time

·    Visual quality of life using the Children’s Visual Function Questionnaire (CVFQ)

Pulmonary function related to airway plexiform neurofibromas

·    Extrathoracic/upper airway lesions (using oscillometry)

Airway resistance at 10 Hz (R10)

·    Intrathoracic/peripheral airway lesions (using spirometry)

o  Preschool Children

§  Forced expiratory volume in 0.75 seconds (FEV0.75)

o  All others

§  Forced expiratory volume in 1 second (FEV1)

·   Extrathoracic/upper airway lesions (using oscillometry)

Airway resistance at 5 or 20 Hz (R5, R20)

o  Airway reactance at resonant frequency

o  Airway reactance at 5, 10, and 20 Hz

·    Intrathoracic/peripheral airway lesions (using spirometry)

Forced vital capacity (FVC)

o  Peak expiratory flow (PEF)

o  Forced expiratory flows

·    Possibly imaging, patient-reported, or quality of life measures

Sleep related to airway plexiform neurofibromas

·    Apnea Hypopnea Index (AHI)

·   Oxygen saturation and hypercapnia during sleep

·   End-tidal CO2

·   Arousal index

Measurement of cNFs


·    General recommendations for measuring cNF

High-frequency ultrasound (HFUS)

·    Linear measures (width and depth) for large and small cNF

·    Recommended exploratory measure

o   Sum of maximum depth or width

3D photography

·    Measurement of surface area for large cNF (≥5 mm)—preferred

·    Linear measures for small cNF (<5 mm)

·    Changes in appearance (coloration) of cNF

·    Recommended exploratory measures

o   Linear measurement (longest diameter)

o   Measurement of volume

o   Sum of surface area for all cNF

Digital calipers

·    Longest diameter (linear measure)

o  Digital calipers are not recommended for cNF <5 mm or for height measurements

·    Recommended exploratory measure

o   Sum of longest diameter

Neurocognitive Outcomes

Attention in school age children/adults and preschool age

·    Performance measure of attention for school age children and adults

o  Digit Span (DS) from the Wechsler scales (Wechsler Intelligence Scale for Children and Wechsler Adult Intelligence Scale)

·    Behavioral problems associated with attention for school age children and adults

Conners Parent Rating Scale-3 (Conners 3) for school age children

Conners Adult ADHD Rating Scale (CAARS) for adults

·    Behavioral problems associated with attention for preschool age children

Attention Deficit Hyperactivity Disorder Rating Scale-Preschool (ADHD-RS-P) for preschool children

·    Important points regarding measure choice

·    Performance measure of attention for preschool age children

NIH Toolbox tasks [Flanker, Dimension Change Card Sort (DCCS), List Sort Working Memory (LSWM)]

Differential Ability Scales—2ndedition (DAS-II) Recall of Digits Forward

Social skills

·    Broader social functioning and prosocial behaviors

Social Skills Improvement System-Rating Scales (SSIS-RS)

·    Problematic social behaviors associated with autism spectrum disorder (ASD)

Social Responsiveness Scale, Second Edition (SRS-2)

Patient-Reported Outcomes


·    Self-Assessment of Communication (SAC) for adults ages 20 and older and the Self-Assessment of Communication–Adolescent (SAC-A) for children and adolescents ages 11-19

Pain intensity

·    Numerical Rating Scale (NRS-11)

Pain interference

·    Pain Interference Index (PII) for children and adolescents

·    Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale for adults

Physical functioning

·    PROMIS Physical Functioning Scale

General quality of life

·    Functional Assessment of Cancer Therapy–General (FACT-G) for adult-only medical trials

·    World Health Organization Quality of Life–BREF (WHOQoL-BREF) for adult-only psychosocial trials

·    Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales (GCS) and Infant Scales for medical and psychosocial NF trials that enroll only children and adolescents or a wider age range from children through adults

NF1-specific quality of life

·    Pediatric Quality of Life Inventory (PedsQL) NF1 module

NF2-specific quality of life

·    NF2 Impact on Quality of Life (NFTI-QOL) for all NF2 clinical trials

·    Recommended exploratory measure for NF2 trials targeting vestibular schwannomas

Penn Acoustic Neuroma Quality of Life (PANQoL)

Tumor Response

Benign tumor response (particularly plexiform neurofibromas and vestibular schwannomas)

·    3D volumetric response on MRI using a specific acquisition protocol (Table e-1)

·    Evaluation for clinical benefit including patient-reported and functional outcomes

External weblinks are provided as a convenience and for informational purposes only.  The REiNS Collaboration does endorse, warrant, or guarantee the products, services, or information described or offered at external sites.  Please contact the external site for answers to questions regarding its content.

Last updated by Little, Paige (NIH/NCI) [F] on Apr 14, 2023