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

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.

Figure 1.

Patients included in our analysis. Seventy-six patients with histologically confirmed MPNST were identified, of which 11 were excluded due to not receiving any treatment for their diagnosed MPNST or were lost to follow-up. A total of 65 patients were included in our analysis. Abbreviation: XRT = radiation therapy

Figure 2.

Clinical outcomes after upfront therapy. Patients are segregated as having received treatment modalities including surgery, radiation, or chemotherapy, or any combination of these, as indicated in the UpSet plot. The immediate clinical outcome following upfront therapy for each patient was then categorized as remission, local or metastatic relapse, progressive disease while on therapy, or death.

Figure 3.

Time on therapy and time to progression associated with the chemotherapy regimens used in the treatment for MPNST as (A) first-line chemotherapy among 48 patients; and (B) salvage chemotherapy among 20 patients. Time on therapy includes time from start to end of therapy, in days. Time to progression or death includes time from start of therapy to the event, also measured in days. Where more than 1 patient received a regimen, values are reported as average (range in days); if only 1 patient received the regimen, the value in days is indicated for that patient. Some patients received multiple regimens as different lines of chemotherapy (second, third, fourth, fifth, or sixth), and these are indicated by color as shown in legend. Abbreviations: ifos = ifosfamide, dox = doxorubicin, etop = etoposide, gem = gemcitabine, IT = irinotecan, temozolomide, VIT = vincristine, irinotecan, temozolomide. *Ranges are included in groups that include more than 1 patient, but are not calculated for patients who remained on therapy at date of data cutoff. ^#2 of the 4 patients received this drug on study. ^{^}1 of the 10 patients received this drug on study. ^&Received this drug through single-patient compassionate use based on the patient’s tumor genetic testing results. ^%To date, the results from included clinical trials have not been published.

Figure 4.

Sequence of salvage chemotherapy regimens used for patients with relapsed or refractory MPNST. Modified swimmer’s plot representation includes patients (n = 20) who received at least 2 lines of systemic chemotherapy (including conventional or cytotoxic chemotherapy, targeted agents, or immunotherapy). Time starts at the beginning of the second-line systemic therapy. Regimens are shown in color, as indicated in the legend. White space indicates that the patient did not receive treatment during that time. Events are indicated by black symbols as shown in legend. Abbreviations: dox = doxorubicin, etop = etoposide, gem = gemcitabine, IT = irinotecan, temozolomide, VIT = vincristine, irinotecan, temozolomide.