Cancer Res Treat.  2017 Jul;49(3):717-726. 10.4143/crt.2016.271.

Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1

• Hwang IK
• Hahn SM
• Kim HS
• Kim SK
• Kim HS
• Shin KH
• Suh CO
• Lyu CJ
• Han JW

• KMID: 2388317
• DOI: http://doi.org/10.4143/crt.2016.271

Abstract

PURPOSE
Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs.
MATERIALS AND METHODS
The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared.
RESULTS
Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS.
CONCLUSION
NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.

Keyword

Sarcoma; Neurilemmoma; Neoplasms; Neurofibromatoses

MeSH Terms

Humans
Korea
Multivariate Analysis
Neoplasm Metastasis
Neurilemmoma*
Neurofibromatoses*
Neurofibromatosis 1*
Pathology
Sarcoma
Seoul

Figure

• 

  Fig. 1. Scheme of first-line treatment modalities. sMPNST, sporadic malignant peripheral nerve sheath tumors; NF-MPNST, malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1; Chemo, chemotherapy; RT, radiotherapy; Both, chemotherapy and radiotherapy; NED, no evidence of disease; R0/R1/2, resection margin, see details in Materials and Methods section; Tx, treatment; F/U, follow-up.

• 

  Fig. 2. Overall survival of patients with malignant peripheral nerve sheath tumors.

• 

  Fig. 3. Overall survival according to neurofibromatosis type 1 (NF-1) status. (A) Overall survival associated with nonmetastatic malignant peripheral nerve sheath tumors. (B) Overall survival associated with metastatic malignant peripheral nerve sheath tumors.

• 

  Fig. 4. Overall survival according to the risk factors. (A) Overall survival associated with the margin status (positive vs. negative). (B) Overall survival associated with the pathologic grade (not acquired [N/A] vs. G1 vs. G2 vs. G3). (C) Overall survival associated with the metastatic status (localized vs. metastasis).

Reference

References

1. Amirian ES, Goodman JC, New P, Scheurer ME. Pediatric and adult malignant peripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and end results program. J Neurooncol. 2014; 116:609–16.

2. Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM. Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology. 2005; 65:205–11.

3. Ferner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002; 62:1573–7.

4. Baehring JM, Betensky RA, Batchelor TT. Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment. Neurology. 2003; 61:696–8.

5. Carli M, Ferrari A, Mattke A, Zanetti I, Casanova M, Bisogno G, et al. Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol. 2005; 23:8422–30.

6. Stucky CC, Johnson KN, Gray RJ, Pockaj BA, Ocal IT, Rose PS, et al. Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol. 2012; 19:878–85.

7. LaFemina J, Qin LX, Moraco NH, Antonescu CR, Fields RC, Crago AM, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol. 2013; 20:66–72.

8. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014; 13:834–43.

9. 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):608–14.

10. Gutmann DH, McLellan MD, Hussain I, Wallis JW, Fulton LL, Fulton RS, et al. Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma. Genome Res. 2013; 23:431–9.

11. Porter DE, Prasad V, Foster L, Dall GF, Birch R, Grimer RJ. Survival in malignant peripheral nerve sheath tumours: a comparison between sporadic and neurofibromatosis type 1-associated tumours. Sarcoma. 2009; 2009:756395.

12. Kolberg M, Holand M, Agesen TH, Brekke HR, Liestol K, Hall KS, et al. Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol. 2013; 15:135–47.

13. Cashen DV, Parisien RC, Raskin K, Hornicek FJ, Gebhardt MC, Mankin HJ. Survival data for patients with malignant schwannoma. Clin Orthop Relat Res. 2004; (426):69–73.

14. Yu J, Deshmukh H, Payton JE, Dunham C, Scheithauer BW, Tihan T, et al. Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res. 2011; 17:1924–34.

15. Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, et al. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer. 2006; 107:1065–74.

16. Zou C, Smith KD, Liu J, Lahat G, Myers S, Wang WL, et al. Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg. 2009; 249:1014–22.

17. Deyrup AT, Weiss SW. Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world. Histopathology. 2006; 48:42–50.

18. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010; 17:1471–4.

19. Zehou O, Fabre E, Zelek L, Sbidian E, Ortonne N, Banu E, et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review. Orphanet J Rare Dis. 2013; 8:127.

20. Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002; 39:311–4.

21. deCou JM, Rao BN, Parham DM, Lobe TE, Bowman L, Pappo AS, et al. Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol. 1995; 2:524–9.

22. Hegedus B, Banerjee D, Yeh TH, Rothermich S, Perry A, Rubin JB, et al. Preclinical cancer therapy in a mouse model of neurofibromatosis-1 optic glioma. Cancer Res. 2008; 68:1520–8.

23. Kahn J, Gillespie A, Tsokos M, Ondos J, Dombi E, Camphausen K, et al. Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Front Oncol. 2014; 4:324.

24. Sordillo PP, Helson L, Hajdu SI, Magill GB, Kosloff C, Golbey RB, et al. Malignant schwannoma: clinical characteristics, survival, and response to therapy. Cancer. 1981; 47:2503–9.

25. Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986; 57:2006–21.

26. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist. 2000; 5:477–85.

27. Meehan RS, Chen AP. New treatment option for ovarian cancer: PARP inhibitors. Gynecol Oncol Res Pract. 2016; 3:3.

28. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015; 14:733–45.

29. Colman SD, Williams CA, Wallace MR. Benign neurofibromas in type 1 neurofibromatosis (NF1) show somatic deletions of the NF1 gene. Nat Genet. 1995; 11:90–2.

30. Carroll SL. The challenge of cancer genomics in rare nervous system neoplasms: malignant peripheral nerve sheath tumors as a paradigm for cross-species comparative oncogenomics. Am J Pathol. 2016; 186:464–77.