NF1- and non-NF1–associated malignant peripheral nerve sheath tumors (MPNST): The University of Texas MD Anderson (MDACC) experience.

Abstract

11576 Background: MPNSTs are aggressive sarcomas with poor prognosis due to their high propensity for metastasis, rapid growth and limited response to standard chemotherapy (CT). While commonly associated with neurofibromatosis type 1 (NF1), they can also occur sporadically (non-NF1). This study aims to evaluate baseline characteristics and outcomes in NF1 and non-NF1 associated MPNST in order to understand CT effectiveness and set a benchmark for future therapies. Methods: A retrospective chart review was conducted at MDACC, including 258 patients diagnosed with MPNST (173 NF1 and 85 non-NF1). Data collected included demographic information, primary tumor location and size, disease stage at diagnosis (localized vs. metastatic), efficacy of CT regimens utilized, and survival data. Descriptive statistics were used to summarize patient characteristics. Chi squared tests or Fisher’s exact tests, and t-test/ANOVA were used to compare patient’s characteristics and distributions of overall survival (OS), and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: Median age at diagnosis was 33 yrs (IQR 22-44) and 50 yrs (IQR 38-61), and median tumor size at diagnosis 7.4cm and 6.3cm for the NF1 and non-NF1 cohorts, respectively. Tumors were most commonly located in the trunk, followed by the lower extremity, with head and neck involvement more frequent in non-NF1 cases. Metastatic disease was present at diagnosis in 28.3% of NF1 (49/173) and 22.4% (19/85) of non-NF1 cases. Adriamycin with Ifosfamide (AI) was the most utilized first-line CT regimen while gemcitabine plus docetaxel was the preferred second-line regimen. 154 patients, 87 patients, and 37 patients received frontline, second-line, and third-line CT, respectively. Median PFS for front-line CT was 8.0 months (4.7, NR) for patients with metastatic disease at presentation and 11.7 months (8.94, NR) for patients who received AI. Median OS was 2.34 yrs (1.88, 3.15) vs 1.81 yrs (0.89, 3.76) for NF1 and non-NF1 cohorts (p = 0.038), respectively. 5-yr OS was 42% (33, 51) for local disease and 9% (3, 19) for metastatic disease at presentation. Additional analysis of PFS by NF1 status, lines of therapy, and regimen will be presented at the conference. Conclusions: Patients with metastatic MPNST have dismal outcomes and CT efficacy and utilization drops after frontline treatment. These findings highlight the importance of early diagnosis and tailored novel therapeutics for MPNST patients.