Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1

Abstract

There are conflicting reports as to whether malignant peripheral nerve sheath tumor (MPNST) patients with neurofibromatosis type 1 (NF1) have worse prognosis than non-NF1 MPNST patients. Large clinical studies to address this problem are lacking due to the rareness of MPNST. We have performed meta-analyses testing the effect of NF1 status on MPNST survival based on publications from the last 50 years, including only nonoverlapping patients reported from each institution. In addition, we analyzed survival characteristics for 179 MPNST patients from 3 European sarcoma centers. The meta-analyses including data from a total of 48 studies and >1800 patients revealed a significantly higher odds ratio for overall survival (OR(OS)) and disease-specific survival (OR(DSS)) in the non-NF1 group (OR(OS) = 1.75, 95% confidence interval [CI] = 1.28-2.39, and OR(DSS) = 1.68, 95% CI = 1.18-2.40). However, in studies published in the last decade, survival in the 2 patient groups has been converging, as especially the NF1 group has shown improved prognosis. For our own MPNST patients, NF1 status had no effect on overall or disease-specific survival. The compiled literature from 1963 to the present indicates a significantly worse outcome of MPNST in patients with NF1 syndrome compared with non-NF1 patients. However, survival for the NF1 patients has improved in the last decade, and the survival difference is diminishing. These observations support the hypothesis that MPNSTs arising in NF1 and non-NF1 patients are not different per se. Consequently, we suggest that the choice of treatment for MPNST should be independent of NF1 status.

Fig. 1.

Kaplan–Meier plots for 5-year OS (A), DSS (B), and DFS (C) from MPNST patients with NF1 (n = 62, red lines) and without NF1 (n = 117, blue lines).

Fig. 2.

Flowchart of literature review and study selection for meta-analyses.

Fig. 3.

Meta-analyses of OR for mortality from MPNST in NF1 patients compared with non-NF1 patients using OS (A and C) and DSS (B and D) as clinical endpoints, and 1963 to present (A and B) and 2001 to present (C and D) as publication time frames. The OR for each study is represented by a square; horizontal lines represent 95% CIs. The size of the square represents the weight (inverse variance). The diamonds represent the pooled ORs using a random effects model.

Fig. 4.

Kaplan–Meier plots comparing time dependency of 5-year OS for MPNST patients with NF1 (red lines) and without NF1 (blue lines). Thick lines include studies published after 2000 (n = 207 NF1 and n = 246 non-NF1) and thin lines include studies published between 1963 and 2000 (n = 191 NF1 and n = 266 non-NF1).