Observational Study of the Real-world Effectiveness and Safety of Selumetinib Treating Adult Patients With Neurofibromatosis Type 1 (NF1) Who Have Symptomatic, Inoperable Plexiform Neurofibroma (PN)

1. Willing and able to provide written informed consent to participate in the study.
2. Participants must be ≥ 18 years at the time of screening.

3. All participants must have a diagnosis of NF1 with symptomatic, inoperable PN where:

   a)Participants must have PN and at least one other diagnostic criterion for NF1 [18]: (i)Six or more café-au-lait spots (> 5 mm in greatest diameter in pre-pubertal participants or > 15 mm in greatest diameter in post-pubertal participants) (ii)Freckling in the axillary or inguinal region

   • At least one of the two pigmentary findings (cafe-au-lait macules or freckling) should be bilateral (iii)Two or more iris Lisch nodules identified by slit lamp examination or 2 or more choroidal abnormalities-defined as bright, patchy nodules imaged by optical coherence tomography/near-infrared reflectance imaging (iv)Optic pathway glioma (v)A distinctive osseous lesion such as sphenoid dysplasia, anterolateral bowing of the tibia, or pseudoarthrosis of a long bone
   • Sphenoid wing dysplasia is not a separate criterion in case of an ipsilateral orbital PN.

   (vi)A NF1 heterozygous pathogenic variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells (vii)A parent with NF1 by the above criteria b)Target PN [15] is defined as a PN that is measurable (i.e. a PN of at least 3cm measured in one dimension, which can be seen on at least 3 imaging slices, and has a reasonably well-defined contour), symptomatic, and considered inoperable. Regular MRI/ Contrast-enhanced MRI/DCE-MRI/WB-MRI analysis might be performed on the target PN for volumetric analysis. If multiple PNs are present, the investigator will select the PN that is most clinically relevant (e.g., causing the predominant symptom) as the target PN.

   c)Inoperable is defined as a PN that cannot be completely surgically removed without a risk of substantial morbidity (including significant bleeding or damage to nerves and/or surrounding vital structures) due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN; or unacceptable risk from the general anesthetic as assessed by the investigator.

   d)Symptomatic is defined as clinically significant symptoms caused by the PN, as judged by the investigator; symptoms may include, but are not limited to, pain, motor dysfunction, and disfigurement.

4. Have a documented treatment plan or prescription for selumetinib in the medical records as assessed by the investigator, indicating the decision to initiate selumetinib treatment.
5. The first dose of selumetinib is administered within 28 days after ICF.

Exclusion Criteria:

1. Participants with any evidence of a life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, makes it undesirable for the participants to participate in the study.
2. Participants with a confirmed or suspected malignant glioma or MPNST, or with a prior malignancy or other cancer requiring treatment with chemotherapy or radiation therapy.
3. Inability to undergo MRI and/or contraindication for MRI examinations.
4. Have had prior treatment with a MEKi, Ras or Raf inhibitor.
5. Currently enrolled in any interventional clinical trial at the time of enrolment or initiation of selumetinib.
6. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
7. Judgment by the investigator that the participant will not be able to adequately understand or consistently complete ePRO instruments.
8. Pregnant or breastfeeding women.
9. Male participants or female participants of childbearing potential who have childbearing plans (currently or within the next 3 months).