Enrico Martin

52 Chapter 3 Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas (STS), accounting for 2% of all STS. 1 While 23-51% of MPNSTs occur in neurofibromatosis type 1 (NF1) patients, they can also be sporadic or radiation- induced. 2–5 MPNSTs can originate within a neurofibroma which can lead to diagnostic challenges, particularly in NF1 patients. 6,7 MPNSTs can also present with heterologous elements such as rhabdomyoblastic differentiation, so-called Triton tumors, which reportedly have been associated with poorer survival. 8,9 To date, surgery is the only proven therapy increasing survival in localized MPNST. 3,10 As in other STS, radiotherapy is commonly administered in order to improve local control, but no effect has been shown on survival. 3,11,12 Neoadjuvant administration of radiotherapy is increasing in popularity as it decreases radiation fields and dosage which results in lower long-term toxicities, yet postoperative wound complications are more common. 13,14 Recent studies have shown that neoadjuvant chemotherapy may be considered in high-grade, large, and deep MPNSTs. 15,16 Despite curative intents of treatment in localized MPNST survival remains poor. 2,3,10 Understanding factors associated with survival of this rare sarcoma may ameliorate clinical decision-making. Using a Dutch nationwide cohort of patients, this study aims to investigate overall survival and prognostic factors for overall survival in non- retroperitoneal and retroperitoneal MPNSTs. Methods Patient population Data of patients treated between 1989- 2017 were obtained from the nationwide Netherlands Cancer Registry (NCR), which is managed by the Netherlands Comprehensive Cancer Organisation (IKNL). The NCR is a population-based registry that gets notified of all newly diagnosed malignancies in the Netherlands by automated pathological archive (PALGA) and the National Registry of Hospital Discharge Diagnosis (LMR). Patient and tumor characteristics and initial treatment information are routinely extracted from medical records by uniformly trained registrars and enhanced by computerized consistency checks at both regional and national levels. Full pathological reports were also requested from PALGA. 17 The data request was approved by the scientific and privacy committees of IKNL. MPNSTs from any site were obtained from the registry. Cases were matched to PALGA by means of a trusted third party, which allows all pathological reports from a single patient to be matched. All pathological reports were reviewed to see if a final diagnosis of MPNST was made in each patient;