Analysis of treatment sequence and outcomes in patients with relapsed malignant peripheral nerve sheath tumors

Lindy Zhang; Kathryn M Lemberg; Ana Calizo; Ravi Varadhan; Alan H Siegel; Christian F Meyer; Jaishri O Blakeley; Christine A Pratilas

doi:10.1093/noajnl/vdad156

Analysis of treatment sequence and outcomes in patients with relapsed malignant peripheral nerve sheath tumors

Neurooncol Adv. 2023 Dec 2;5(1):vdad156. doi: 10.1093/noajnl/vdad156. eCollection 2023 Jan-Dec.

Authors

Lindy Zhang^{1

2}, Kathryn M Lemberg^{1

3}, Ana Calizo², Ravi Varadhan¹, Alan H Siegel³, Christian F Meyer¹, Jaishri O Blakeley^{1

4}, Christine A Pratilas^{1

3}

Affiliations

¹ Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Neurology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Background: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas originating from cellular components within the nerve sheath. The incidence of MPNST is highest in people with neurofibromatosis type 1 (NF1), and MPNST is the leading cause of death for these individuals. Complete surgical resection is the only curative therapeutic option, but is often unfeasible due to tumor location, size, or presence of metastases. Evidence-based choices of chemotherapy for recurrent/refractory MPNST remain elusive. To address this gap, we conducted a retrospective analysis of our institutional experience in treating patients with relapsed MPNST in order to describe patient outcomes related to salvage regimens.

Methods: We conducted a retrospective electronic health record analysis of patients with MPNST who were treated at Johns Hopkins Hospital from January 2010 to June 2021. We calculated time to progression (TTP) based on salvage chemotherapy regimens.

Results: Sixty-five patients were included in the analysis. Upfront therapy included single or combined modalities of surgery, chemotherapy, or radiotherapy. Forty-eight patients received at least 1 line of chemotherapy, which included 23 different regimens (excluding active clinical studies). Most patients (n = 42, 87.5%) received a combination of doxorubicin, ifosfamide, or etoposide as first-line chemotherapy. Salvage chemotherapy regimens and their TTP varied greatly, with irinotecan/temozolomide-based regimens having the longest average TTP (255.5 days, among 4 patients).

Conclusions: Patients with advanced or metastatic MPNST often succumb to their disease despite multiple lines of therapy. These data may be used as comparative information in decision-making for future patients and clinical trials.

Keywords: chemotherapy; malignant peripheral nerve sheath tumors; neurofibromatosis type 1; salvage therapy; soft tissue sarcoma.