Enrico Martin

81 Treatment and survival in pediatric MPNST therefore incorporated in both the EpSSG and the Children’s Oncology Group (COG) guidelines. The benefit of chemotherapy in an adjuvant setting is however less clear. Some studies have suggested its use in large, high-grade STS including MPNSTs. 14,42,47 Ideal cytotoxic regimens include a combination of doxorubicin and ifosfamide as they have shown to give the best effect in both adult and pediatric MPNST. 6,32,33,48 Yet response rates in MPNSTs are still very low, even more so in NF1 patients. 6,16,32,33 Given the low chemosensitivity of MPNSTs, novel therapies are desperately warranted. Currently, multiple new therapies are under investigation, including targeted therapies, immunotherapy, and oncolytic viruses. 49 However, to date no targeted therapy has been proven effective in MPNST patients. 50–55 Strengths and limitations This study is based on registry and pathological data only and subsequently resulting in some limitations. NF1 status is not routinely registered in the NCR and all diagnoses were made based on pathological reports. This has possibly resulted in an underestimation of the total amount of NF1 patients. However, the incidence rate in this study is in concordance to other series. 6,15,24,25 Tumor size was also commonly missing, which may have underestimated the effect of tumor size on survival in this study. Tumor grade could also not be analyzed because of its heterogeneity in reporting. Nonetheless have low-grade tumors only recently been defined following a consensus meeting. 56 Other clinical information such as the efficacy of chemotherapy or radiotherapy on disease-free survival were not available for this study. Nevertheless, using a nationwide cohort of patients, a model for localized pediatric MPNST could be constructed. The advantage of such data is that models may be more generalizable as there is no form of selection or referral bias. The SEER database also allows for analyses of large patient cohorts, but lacks data on NF1 status, tumor depth, R0/R1/R2 resection margins, and the use of chemotherapy. 29,57 It becomes increasingly clear that STS can present very heterogeneously and single histological subtypes may present differently, having additional risk factors which warrant attention. As MPNSTs carry a high risk for postoperative morbidity and oncological treatment failure, more knowledge needs to be gathered from their adult counterparts as well as other high-risk pediatric NRSTS. As such, ideal patient-tailored treatments may be elucidated balancing both oncological and functional outcomes. Conclusion Pediatric MPNST present similarly compared to adult MPNST. In children, NF1 patients will generally present with larger tumors, but are treated similarly compared to non-NF1 MPNSTs. In localized pediatric MPNST, NF1 status is independently associated with poor survival. No treatment related factor was independently associated with survival. Life expectancy has significantly increased in pediatric MPNSTs after 2005. 4