The management of neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors: challenges, progress, and future prospects

ABSTRACT

Introduction: The most common malignancy affecting adults with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive sarcoma that typically develops from a pre-existing benign plexiform neurofibroma. These tumors are difficult to treat, with limited therapeutic options and poor patient responses, leading to unacceptably high mortality rates. Despite advances in our understanding of the pathogenesis of these tumors, the overall prognosis for these cancers remains dismal.

Areas covered: This paper reviews the cellular and molecular etiologies underlying MPNST development and progression, the diagnostic workup of patients with these malignancies, and the current and investigational treatment options. Areas of controversy in which further research is needed will be highlighted.

Expert opinion: MPNSTs remain a therapeutic challenge. Multidisciplinary care at a high volume sarcoma center is essential for optimal outcomes. Further work is needed to develop targeted combinational therapies for these tumors.

KEYWORDS:

• Atypical neurofibromas
• malignant peripheral nerve sheath tumors neurofibromatosis
• plexiform neurofibromas

Article highlights

• MPNSTs are aggressive soft tissue sarcomas which represent a challenge to diagnose and treat

• Surgery remains the only curative therapy

• The use of adjuvant or neoadjuvant radiation is accepted to prevent local recurrence

• The use of adjuvant or neoadjuvant chemotherapy remains an area of controversy

• Treatment of metastatic disease is limited to cytotoxic chemotherapy or enrollment on a clinical trial

• Treatment of these tumors at a high volume center with multidisciplinary care is essential

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

Dr. Hirbe is funded by a SARC (Sarcoma Alliance for Research through Collaboration) career development award.