Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease

Abstract

Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients. Methods This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients. Results Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment. Conclusion Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.

Sciatic Nerve Tumor: Malignant Peripheral Nerve Sheath Tumor: Case Report

“…Chemotherapy has a limited role in MPNST, primarily in NF1-associated MPNST and has not yet been fully established. In a scenario where MPNST is estimated in negative margins, surgery alone cannot achieve desired outcomes, and radiotherapy and adjuvant chemotherapy are applied (15) .…”

Case report: First case of undifferentiated embryonal sarcoma of the liver in a child with neurofibromatosis type 1, treated by hepatic chemoperfusion with transcatheter arterial chemoembolization

“…The current case provides a unique example of UESL developing in the clinical context of NF1. According to the literature, UESL typically harbor translocations t ( 11 , 13 ) (q13.1;q13.42) involving MALAT1 or t ( 2 , 13 )(q31.1;q13.42) involving AK023515 , an uncharacterized noncoding gene; alternatively, an inv ( 13 , 13 )(q13.42;q13.43) inversion involving a Kruppel-type zinc-finger protein-encoding gene PEG3 may be encountered ( 18 , 19 ). These tumors may also harbor mutations in TP53 including somatic deletions and missense substitutions ( 19 ).…”

“…The NF1-associated tumorigenesis conventionally involves biallelic inactivation of NF1 , which encodes the neurofibromin protein involved in regulation of several cytoplasmic cascades, notably the RAS/RAF/MEK/ERK signaling pathway ( 1 ). MPNST, which predominantly arise within preexisting plexiform neurofibromas, are encountered in about 10% of patients with NF1 ( 2 ).…”

Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces for Prophylactic Pain Control in Neurofibromatosis Type 1 Amputees

“…With the high rates of neurofibroma recurrence, and painful neuroma symptoms after traditional traction neurectomy or excision, this anecdotal evidence supports prophylactic nerve measures at the time of intervention. 2,12 Therefore, TMR and RPNI should be considered in future treatment for amputated nerve in NF1 patients.…”