Disease burden and unmet needs

Disease Burden of NF1-PN

Possible impact on daily life

Patients affected by NF1-PN and their caregivers often face a reduction in quality of life that extends beyond the physical symptoms of the condition.

This complex condition can result in a wide array of physical, psychological and cognitive limitations that can affect daily functioning and overall well-being.1–3
Physical symptoms
  • Pain
  • Impaired mobility
  • Disfigurement
  • Visual impairment
  • Airway obstruction
  • Spinal cord compression
  • Tumours putting pressure on organs
Psychological impact
  • Depression
  • Anxiety
  • Isolation
  • Stigma
  • Embarrassment
  • Fear of cancer
  • Impaired sexual health
Cognitive deficits
  • Inability to focus
  • Impaired memory
  • Impaired visual and motor function
  • Learning disabilities

Pain and Disfigurement: Key Concerns Across Ages

Across all age groups, two of the most frequently reported concerns among NF1-PN patients are potential pain and potential changes in physical appearance.3

In children and adolescents, pain has been found to impact their quality of life, even when pain medications are used.4

NF1-PN: a complex clinical challenge
Tumour Growth and Distribution
Plexiform neurofibromas (PNs) are complex tumours that can develop anywhere in the body outside the central nervous system (CNS). The most common sites of occurrence are the head and neck area, followed by the extremities and trunk.5,6
The growth behaviour of PNs is unpredictable, with periods of rapid expansion alternating with phases of relative inactivity.7
Surgery to manage NF1-PN is not always feasible, and outcomes can be variable.8
Surgical Management: Limitations and Outcomes

Historically, the primary treatment option for PNs has been surgical resection; however, unresectable tumours, incomplete resections and tumour regrowth may limit the utility of surgical interventions.5
NF1-PN surgery is often restricted by the infiltrative nature of the tumours, their anatomical location and their proximity to nerves and blood vessels.2
Even when surgery is feasible:

  • Complete removal of a plexiform neurofibroma (PN) is not possible in many cases.9
  • Approximately 50% of patients have tumours that cannot be completely resected.10
  • Even after reported complete resections, 20% of tumours may regrow.10
The need for further therapy options
Since surgical treatment is not always possible or has reached its limits, there is still a need for non-surgical treatment options for patients with NF1-PN.

Common sites for PNs5, 6

  1. Copley-Merriman C, Yang X, Juniper M, et al. Natural History and Disease Burden of Neurofibromatosis Type 1 with Plexiform Neurofibromas: A Systematic Literature Review. Adolesc Health Med Ther. 2021;12:55–66.
  2. Fisher MJ, Blakeley JO, Weiss BD, et al. Management of neurofibromatosis type 1-associated plexiform neurofibromas. Neuro Oncol. 2022;24(11):1827–1844.
  3. Lai J-S, Jensen SE, Patel ZS, Listernick R, Charrow J. Using a qualitative approach to conceptualize concerns of patients with neurofibromatosis type 1 associated plexiform neurofibromas (pNF) across the lifespan. Am J Med Genet A. 2017;173(1):79–87.
  4. Wolters PL, Burns KM, Martin S, et al. Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life. Am J Med Genet A. 2015;167A(9):2103–2113.
  5. Prada CE, Rangwala FA, Martin LJ, et al. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012;160(3):461–467.
  6. Darrigo LG Jr, Ferraz VEF, Cormedi MCV, et al. Epidemiological profile and clinical characteristics of 491 Brazilian patients with neurofibromatosis type 1. Brain Behav. 2022;12(6):e2599.
  7. Nguyen R, Dombi E, Widemann BC, et al. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012:7:75.
  8. Ejerskov C, Farholt S, Nielsen FSK, et al. Clinical characteristics and management of children and adults with neurofibromatosis type 1 and plexiform neurofibromas in Denmark: a nationwide study. Oncol Ther. 2023;11(1):97–110.
  9. Yang X, Desai K, Agrawal N, et al. Treatment, resource use and costs among pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas. Pediatric Health Med Ther. 2020;11:421–428.
  10. Armstrong AE, Belzberg AJ, Crawford JR, et al. Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas. BMC Cancer. 2023;23(1):553.