ORIGINAL RESEARCH ARTICLE
Multimodality Treatment in Malignant Peripheral Nerve Sheath Tumors
Received Date : 04 Sep 2019
Accepted Date : 15 Dec 2019
Available Online : 10 Feb 2020
Doi: 10.37047/jos.2019-73127 - Article's Language: EN
J Oncol Sci. 2020;6(1):23-8
Objective: Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas with poor prognosis. The treatment
options, especially in metastatic cases, are limited. In this study, we aimed to investigate the treatment outcomes along with programmed
death-ligand 1 (PD-L1) expression as a potential surrogate for immunotherapy benefit in our patients with MPNST. Material and Methods:
In this retrospective study, 27 patients diagnosed with MPNST and treated at the Hacettepe University Cancer Institute between 2000 and 2016
were evaluated. Patient and tumor characteristics, survival data and treatment modalities were obtained from medical charts. The patient outcomes
were assessed based on the treatment modality. Slides prepared from 4-mm diameter microarray tissue were stained for the PD-L1 antibody
using Leica Bond Autostainer (Cell Signaling, E1L3N®). Membranous staining more than 5% of the cells were accepted as positive.
Results: The median age of the patients was 36 years (range 19-89 years), and 37% of patients were male. The median tumor size was 8.7
cm, and 62% of patients had high-grade tumors. The most common tumor localizations were extremities (41%), trunk (48%), and the headneck
region (11%). Only two patients (7%) had distant metastases at the time of diagnosis. Seven patients (26%) had neurofibromatosis type
1 (NF1) and the presence of NF-1 was associated with partially worse overall survival (p=0.056). The majority of the patients underwent primary
surgery (96.3%), and R0-R1 resection was achieved by 76% of patients. The median follow-up was 16 months (range 1 to 178 months).
During the follow-up, 16 patients (59%) had recurrence (37% local, 22% distant recurrence). A 3-year disease-free survival (DFS) rate according
to R0-R1 and R2 resection was 57% vs. 17%, respectively (p<0.001). After surgery, 48% of the patients received adjuvant therapy.
Two patients (7%) received only chemotherapy, five patients (19%) received only radiotherapy (RT), and six patients (22%) received both.
Patients who received both chemotherapy and RT had longer DFS compared to those who received either therapy alone and to those who received
no adjuvant therapy (3-year DFS 100% vs. 14% vs. 44%, respectively, p=0.003) (Figure 3). PD-L1 expression was positive in 6 of 15
patients (40%) and was not associated with DFS. Conclusions: Multimodality treatment with surgery, chemotherapy, and RT may improve
DFS in patients with MPNSTs. The PD-L1 expression is not associated with DFS.
Keywords: Malignant peripheral nerve sheath tumor; multimodality treatment; PD-L1 expression
- Lin CT, Huang TW, Nieh S, Lee SC. Treatment of a malignant peripheral nerve sheath tumor. Oncologie. 2009;32(8-9):503-505. [Crossref] [PubMed]
- Weiss S, Goldblum J. Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor family. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, St Louis, MO; 2007:963-979.
- Ferner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002;62(5):1573-1577.
- Dunn GP, Spiliopoulos K, Plotkin SR, et al. Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis type 1. J Neurosurg. 2013;118(1):142-148. [Crossref] [PubMed]
- Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986;57(10):2006-2021. [Crossref]
- Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39(5):311-314. [Crossref] [PubMed] [PMC]
- Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman J. Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology. 2005;65(2):205-211. [Crossref] [PubMed]
- Beert E, Brems H, Daniëls B, et al. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer. 2011;50(12):1021-1032. [Crossref] [PubMed]
- Okcu M, Hicks J, Merchant T, Andrassy R, Pappo A, Horowitz M. Nonrhabdomyosarcomatous soft tissue sarcomas. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:1033-1073.
- Eilber FC, Brennan MF, Eilber FR, Dry SM, Singer S, Kattan MW. Validation of the postoperative nomogram for 12‐year sarcoma‐ specific mortality. Cancer. 2004;101(10):2270-2275. [Crossref] [PubMed]
- Carli M, Ferrari A, Mattke A, et al. Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol. 2005;23(33):8422-8430. [Crossref] [PubMed]
- Kaushal A, Citrin D. The role of radiation therapy in the management of sarcomas. Surg Clin North Am. 2008;88(3):629-646. [Crossref] [PubMed] [PMC]
- Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL. Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys. 1998;42(2):351-360. [Crossref]
- Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol. 1998;16(1):197-203. [Crossref] [PubMed]
- Kahn J, Gillespie A, Tsokos M, et al. Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Front Oncol. November 2014;(4):324. [Crossref] [PubMed] [PMC]
- Goertz O, Langer S, Uthoff D, et al. Diagnosis, treatment and survival of 65 patients with malignant peripheral nerve sheath tumors. Anticancer Res. 2014;34(2):777-783.
- Hruban RH, Shiu MH, Senie RT, Woodruff JM. Malignant peripheral nerve sheath tumors of the buttock and lower extremity. A study of 43 cases. Cancer. 1990;66(6):1253-1265. [Crossref]
- Kourea HP, Bilsky MH, Leung DH, Lewis JJ, Woodruff JM. Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clincopathologic study of 25 patients and 26 tumors. Cancer. 1998;82(11): 2191-2203. [Crossref]
- Kösemehmetoğlu K, Özoğul E, Babaoğlu B, Tezel GG, Gedikoğlu G. Programmed death ligand 1 (PD-L1) expression in malignant mesenchymal tumors. Turk Patoloji Derg. 2017;1(1):192-197. [Crossref] [PubMed]
- Paydas S, Bagir EK, Deveci MA, Gonlusen G. Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas. Med Oncol. 2016;33(8):93. [Crossref] [PubMed]
- DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics. 2000;105(3 pt 1):608-614. [Crossref] [PubMed]
- Zou C, Smith KD, Liu J, et al. Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg. 2009;249(6):1014-1022. [Crossref] [PubMed]
- LaFemina J, Qin LX, Moraco NH, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol. 2013;20(1):66-72. [Crossref] [PubMed] [PMC]
- Stucky CC, Johnson KN, Gray RJ, et al. Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol. 2012;19(3):878-885. [Crossref] [PubMed]
- Farid M, Demicco EG, Garcia R, et al. Malignant peripheral nerve sheath tumors. Oncologist. 2014;19(2):193-201. [Crossref] [PubMed] [PMC]
- Kolberg M, Høland M, Ågesen TH, et al. Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol. 2012;15(2):135-417. [Crossref] [PubMed] [PMC]
- Gupta G, Mammis A, Maniker A. Malignant peripheral nerve sheath tumors. Neurosurg Clin N Am. 2008;19(4):533-543. [Crossref] [PubMed]
- Kroep JR, Ouali M, Gelderblom H, et al. First-line chemotherapy for malignant peripheral nerve sheath tumor (MPNST) versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST: an EORTC soft tissue and bone sarcoma group study. Ann Oncol. 2010;22(1):207-214. [Crossref] [PubMed] [PMC]
- James AW, Shurell E, Singh A, Dry SM, Eilber FC. Malignant peripheral nerve sheath tumor. Surg Oncol Clin N Am. 2016;25(4):789-802. [Crossref] [PubMed]
- Hsieh KL, Lu CC, Li CF, Feng YH, Liao AC. Malignant peripheral nerve sheath tumor of prostate: a rare case report and literature review. Case Rep Urol. 2016;2016:9317567. [Crossref] [PubMed] [PMC]
- Hirbe AC, Cosper PF, Dahiya S, Van Tine BA. Neoadjuvant ifosfamide and epirubicin in the treatment of malignant peripheral nerve sheath tumors. Sarcoma. 2017;2017: 3761292. [Crossref] [PubMed] [PMC]
- Gronchi A, Ferrari S, Quagliuolo V, et al. Full-dose neoadjuvant anthracycline+ ifosfamide chemotherapy is associated with a relapse free survival (RFS) and overall survival (OS) benefit in localized high-risk adult soft tissue sarcomas (STS) of the extremities and trunk wall: interim analysis of a prospective randomized trial. European Society for Medical Oncology. 2016;27(6):1-36. [Crossref]
- Jung HI, Lee HU, Ahn TS, et al. Primary hepatic malignant peripheral nerve sheath tumor successfully treated with combination therapy: a case report and literature review. Ann Surg Treat Res. 2016;91(6):327-331. [Crossref] [PubMed] [PMC]
- Durbin AD, Ki DH, He S, Look AT. Malignant peripheral nerve sheath tumors. In: Langenau DM, ed. Cancer and Zebrafish: Mechanisms, Techniques, and Models. 1st ed. Springer; Switzerland; 2016:495-530. [Crossref] [PubMed]
- Kim A, Stewart DR, Reilly KM, Viskochil D, Miettinen MM, Widemann BC. Malignant peripheral nerve sheath tumors state of the science: leveraging clinical and biological insights into effective therapies. Sarcoma. 2017;2017: 7429697. [Crossref] [PubMed] [PMC]
- Ki DH, He S, Rodig S, Look AT. Overexpression of PDGFRA cooperates with loss of NF1 and p53 to accelerate the molecular pathogenesis of malignant peripheral nerve sheath tumors. Oncogene. 2017;36(8):1058-1068. [Crossref] [PubMed] [PMC]
- Widemann BC, Italiano A. Biology and management of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and malignant peripheral nerve sheath tumors: state of the art and perspectives. J Clin Oncol. 2018;36(2):160-167. [Crossref] [PubMed] [PMC]
- Shurell E, Singh AS, Crompton JG, et al. Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes. Oncotarget. 2016;7(39):64300-64308. [Crossref]
- Bertucci F, Finetti P, Perrot D, et al. PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas. OncoImmunology. 2017;6(3): e1278100. [Crossref] [PubMed] [PMC]
- D'Angelo SP, Shoushtari AN, Agaram NP, et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol. 2015;46(3):357-365. [Crossref] [PubMed] [PMC]
- Inaguma S, Wang Z, Lasota J, et al. Comprehensive immunohistochemical study of programmed cell death ligand 1 (PD-L1): analysis in 5536 cases revealed consistent expression in trophoblastic tumors. Am J Surg Pathol. 2016;40(8):1133-1142. [Crossref] [PubMed] [PMC]
- Kim C, Kim EK, Jung H, et al. Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. BMC Cancer. Jul 2016;(16):434. [Crossref] [PubMed] [PMC]
- Kim JR, Moon YJ, Kwon KS, et al. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. PloS One. 2013;8(12): e82870. [Crossref] [PubMed] [PMC]
- Matthew S, Mackinnon AC. Programmed Death-Ligand 1 Expression in Sarcomas, a Clinical a Pathologic Study. Laboratory Investigation; 2016: Nature Publishing Group 75 Varick St, 9th Flr, New York, NY 10013-1917 USA: p.22A-3A.