Clinical Characteristics and Treatment Outcomes of Radiation-Associated and Spontaneous Malignant Peripheral Nerve Sheath Tumor

Abstract

In an IRB approved protocol, we reviewed the clinical characteristics and outcomes of patients treated for malignant peripheral nerve sheath tumor (MPNST) at our institution and sought to characterize the impact of association with prior radiation, clinicopathologic features and treatment modalities on clinical outcomes. We identified 133 patients with MPNST treated at our institution between 1995 and 2015 and collected the clinical information. Overall survival (OS), local control (LC) and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. The multivariate Cox proportional hazards regression was used to analyze survival outcomes and risk variables. With a median follow-up of 35.4 mo (range: 0.7-270.1), the median OS was 70.7 mo (95% CI: 37.6-103.9). There were 71 men and 62 women with a median age of 42 y (range: 7-86). Patients were classified as having either radiation-associated MPNST (raMPNST, n=10) or spontaneous MPNST (sMPNST, n=123). The median time to development of raMPNST from prior malignancy was 15 y (range: 7-38). Prior malignancies in patients developing raMPNST included Hodgkin disease (6), testicular cancer (2), ALL (1), and Wilms disease (1) at a median age of 20 y (range: 4-39). Compared with sMPNST, raMPNST was not related with either NF syndrome (0% in raMPNST vs 37.4% in sMPNST, p=0.015), occurred more frequently in trunk (90.0% vs 36.8%, p=0.003) and as intermediate grade (90% G2 and 10% G3 vs 43.9% G2 and 43.1% G3, p=0.047). The rate of metastatic disease on presentation was similar (10% raMPNST vs 12.8% sMPNST). No significant difference was found in treatment (surgery, radiation or chemotherapy) between raMPNST and sMPNST (p=NS). On univariate analysis, raMPNST showed worse OS (median: 24.3 mo vs 79.6 mo, p=0.006), LC (9.3 vs 71.6, p=0.031) and MFS (9.3 vs 73.6, p=0.031) than sMPNST. Compared with NF associated sMPNST, raMPNST still showed poorer OS (p=0.021), LC (p=0.043) and MFS (p=0.035). On multivariate analysis, older age (HR=1.02, 95% CI: 1.01-1.03, p=0.027), raMPNST (HR=3.22, 95% CI:1.35-7.65, p=0.008), trunk (HR=2.39, 95% CI: 1.18-4.84, p=0.015), positive lymph node (HR=6.80, 95% CI: 2.11-21.88, p=0.001), metastatic disease at diagnosis (HR=3.61, 95% CI: 1.84-7.10, p<0.001) were related with worse OS, whereas surgery (HR=0.41, 95% CI: 0.20-0.86, p=0.018) was associated with improved OS. Among the 116 patients without metastatic disease at diagnosis, primary disease in head or neck (HR=0.36, 95% CI: 0.16-0.78, p=0.010) and radiation therapy (HR=0.29, 95% CI: 0.16-0.53, p<0.001) were correlated with improved LC, while primary disease in trunk was correlated with worse MFS (HR=3.22, 95% CI: 1.33-7.79, p=0.009). Radiation associated MPNSTs appear to be more likely to develop in the trunk (an unfavorable site), have poorer prognosis than spontaneous MPNST including NF associated ones, and warrant further characterization to determine optimal treatment.