Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1–associated, and radiation-associated malignant peripheral nerve sheath tumors

Abstract

Structured Abstract Objective MPNSTs are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of NF1, or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, neurofibromatosis type 1 (NF1)-associated, and radiation (RT)-associated malignant peripheral nerve sheath tumor (MPNST) are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study. Methods Patients (n = 317) were identified through our institutional tumor registry. Clinicopathologic features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathologic features were used to identify adverse predictors of recurrence and survival outcomes. Results Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6% for the high-grade MPNST cohort, respectively. Five-year DSS was lower in NF1-associated and RT-associated compared to sporadic MPNST (48.7%, 40.9%, and 63.0%, respectively; p = 0.140). RT-associated MPNST had worse LRFS than sporadic and NF1-associated subtypes (p = 0.047). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis. Conclusion RT-associated MPNSTs demonstrate poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared to sporadic tumors.

Genomic Status ofMETPotentiates Sensitivity to MET and MEK Inhibition in NF1-Related Malignant Peripheral Nerve Sheath Tumors

“…The lack of effective therapies for MPNSTs remains a significant issue for individuals affected by NF1 (2,3). By examining the evolution of genomic alterations in the case of a single, NF1-related human MPNST, we ascertained the degree of genomic instability that occurs over the course of MPNST treatment and identified targetable drivers of disease progression in MPNSTs.…”

“…Approximately 8–13% of individuals with NF1 will develop malignant tumors, most commonly Malignant Peripheral Nerve Sheath Tumors (MPNSTs). NF1-related MPNSTs are highly aggressive sarcomas that frequently metastasize and have five-year survival rates ranging from 20–50% (2,3). The mainstay of treatment is surgical resection when possible with consideration of chemotherapy and radiation therapy in select cases.…”

NF1+/− Hematopoietic Cells Accelerate Malignant Peripheral Nerve Sheath Tumor Development without Altering Chemotherapy Response

“…Additionally, NF1-assoicated MPNSTs may respond less favorably to cytotoxic chemotherapy, including a standard doxorubicin/ifosfamide combination used for many sarcoma patients (18). It is unknown if the disparity in outcome is due to clinical factors—such as Neurofibromatosis patients presenting later with MPNST due to the challenge of identifying the sarcoma within a patient with multiple large neurofibromas—or if the disparity in outcome is due to intrinsic biological properties of the tumors, such as worse response to chemotherapy (19). A better understanding of the biological differences driven by the MPNST microenvironment in NF1 patients might have important clinical implications that could impact patient care and reveal new cellular targets for MPNST-directed therapy.…”

Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1—a consensus overview

“…High-grade MPNST has the highest risk of sarcoma-specific death [7]. The 5-year overall survival is approximately 20% to 50% [8–10], and outcome is especially dismal in those with unresectable or metastatic disease [11]. Most clinicopathologic series of MPNSTs report NF1-associated MPNSTs to be approximately equally common as sporadic cases [8,11–15].…”