Neurofibromatosis‐associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study

Abstract

Background Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive non‐rhabdomyoblastic soft‐tissue sarcomas (NRSTS) in children. This study set out to investigate clinical presentation, treatment modalities, and factors associated with survival in pediatric MPNST using Dutch nationwide databases. Methods Data were obtained from the Netherlands Cancer Registry (NCR) and the Dutch Pathology Database (PALGA) from 1989 to 2017. All primary MPNSTs were collected. Demographic differences were analyzed between adult and pediatric (age ≤18 years) MPNST. In children, demographic and treatment differences between neurofibromatosis type 1 (NF1) and non‐NF1 were analyzed. A Cox proportional hazard model was constructed for localized pediatric MPNSTs. Results A total of 70/784 MPNST patients were children (37.1% NF1). Children did not present differently from adults. In NF1 children, tumor size was more commonly large (> 5 cm, 92.3% vs 59.1%). Localized disease was primarily resected in 90.6%, and radiotherapy was administered in 37.5%. Non‐NF1 children tended to receive chemotherapy more commonly (39.5% vs 26.9%). Overall, estimated five‐year survival rates of localized NF1‐MPNST was 52.4% (SE: 10.1%) compared with 75.8% (SE: 7.1%) in non‐NF1 patients. The multivariate model showed worse survival in NF1 patients (HR: 2.98; 95% CI, 1.17‐7.60, P = 0.02) and increased survival in patients diagnosed after 2005 (HR: 0.20; 95% CI, 0.06‐0.69, P = 0.01). No treatment factors were independently associated with survival. Conclusion Pediatric MPNSTs have presentations similar to adult MPNSTs. In children, NF1 patients present with larger tumors, but are treated similarly to non‐NF1 MPNSTs. In localized pediatric MPNST, NF1 is associated with worse survival. Promisingly, survival has increased for pediatric MPNSTs after 2005.

Prognosis and Risk Factors for Malignant Peripheral Nerve Sheath Tumor: A Systematic Review and Meta-analysis

“…However, the survival and recurrence of these patients were various in different literatures. Indeed, some factors were found as risk indicators in MPNST related literatures, such as NF 1 mutation [11,13,24,42], negative margin [13,24], non-adoption of adjuvant therapy [22,26], while several literatures [7,14,29,43] failed to nd prognostic power. Considering the disagreement on prognosis and risk factors, we performed the systematic review and meta-analysis to evaluate 5-year OS rate, 5-year EFS and LR rate of MPNST, and to investigate the related risk factors for survival.…”

“…For an Italian study focusing on pediatric patients (n=73) with relapsing MPNST, Bergamaschi, L. et al [28] reported that the survival rate was 15.8% at 5 years which was the lowest rate in our included studies. For non-NF 1 MPNST children (n=44) in the Netherlands, Martin, E. et al [42] showed the highest 5-year survival rate (75.8%) in these cohorts. In this study, the 5-year OS rate was 49% (range, 16%-63%), which consisted with the most published studies.…”

“…With the improvement of survival for the NF1 patients in past years, they considered that the survival difference was diminishing. However, NF 1 status has been reported to be a risk factor for the prognosis of MPNST in some literatures [11,24,42]. Porter, D. E. et al [36] founded that NF 1 was independent predictor of poor outcome due to the genetic pro le affecting aggressive potential, and emphasized the importance of NF 1 in MPNST staging.…”

Prognosis and Risk Factors for Malignant Peripheral Nerve Sheath Tumor: A Systematic Review and Meta-analysis

“…However, the survival and recurrence of these patients were various in different literatures. Indeed, some factors were found as risk indicators in MPNST related literatures, such as NF1 status [11,13,30,48], negative margin [13,30], non-adoption of adjuvant therapy [28,32], while several literatures [7,14,35,49] failed to nd prognostic power. Considering the disagreement on prognosis and risk factors, we performed the systematic review and meta-analysis to evaluate 5-year OS rate, 5-year EFS and LR rate of MPNST, and to investigate the related risk factors for survival.…”

“…With the improvement of survival for the NF1 patients in past years, they considered that the survival difference was diminishing. However, NF 1 status has been reported to be a risk factor for the prognosis of MPNST in some literatures [11,30,48]. Porter, D. E. et al [42] founded that NF 1 was independent predictor of poor outcome due to the genetic pro le affecting aggressive potential, and emphasized the importance of NF 1 in MPNST staging.…”