Annals of Surgical Oncology

, Volume 20, Issue 1, pp 66–72 | Cite as

Oncologic Outcomes of Sporadic, Neurofibromatosis-Associated, and Radiation-Induced Malignant Peripheral Nerve Sheath Tumors

  • Jennifer LaFemina
  • Li-Xuan Qin
  • Nicole H. Moraco
  • Cristina R. Antonescu
  • Ryan C. Fields
  • Aimee M. Crago
  • Murray F. Brennan
  • Samuel Singer
Bone and Soft Tissue Sarcomas

Abstract

Background

Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, after prior radiation therapy (RT), or in association with neurofibromatosis type 1 (NF1). It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST.

Methods

Patients with primary high-grade MPNST from 1982 to 2011 were identified from a prospectively maintained database. Patients with sporadic MPNST were included only if the MPNST was not associated with NF1 or a neurofibroma or if it was immunohistochemically S100-positive.

Results

We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and 14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced tumors and 9.7 cm for NF1-associated and sporadic tumors (P = 0.004). In multivariate analysis, factors associated with worse disease-specific survival (DSS) were larger size (HR 1.08; 95 % CI 1.04–1.13; P < 0.001) and positive margin (HR 3.30; 95 % CI 1.74–6.28; P < 0.001). Age, gender, site of disease, and S100 staining were not associated with DSS. The 3-year and median DSS were similar for NF1 and sporadic cases; combined 3-year DSS was 64 % and median DSS was 8.0 years. For RT-induced tumors, 3-year DSS was 49 % and median DSS was 2.4 years. The relationship between RT association and DSS approached statistical significance (HR 2.29; 95 % CI 0.93–5.67; P = 0.072).

Conclusions

Margin status and size remain the most important predictors of DSS in patients with MPNST. NF1-associated and sporadic MPNSTs may be associated with improved DSS compared with RT-induced tumors.

References

  1. 1.
    Lewis JJ, Leung D, Woodruff JM, Brennan MF. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg. 1998;228:355–65.PubMedCrossRefGoogle Scholar
  2. 2.
    Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14:1679–89.PubMedGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN. Malignant Peripheral Nerve Sheath Tumor: molecular pathogenesis and current management considerations. J Surg Oncol. 2008;97:340–9.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    Huson SM, Compston DA, Clark P, Harper PS. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989;26:704–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Sorensen SA, Mulvihill JJ, Nielsen A. Long-term follow-up of von Recklinghausen neurofibromatosis. Survival and malignant neoplasms. N Engl J Med. 1986;314:1010–5.PubMedCrossRefGoogle Scholar
  9. 9.
    D’Agostino AN, Soule EH, Miller RH. Primary malignant neoplasms of nerves (malignant neurilemomas) in patients without manifestations of multiple neurofibromatosis (Von Recklinghausen’s disease). Cancer. 1963;16:1003–14.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Cashen DV, Parisien RC, Raskin K, Hornicek FJ, Gebhardt MC, Mankin HJ. Survival data for patients with malignant schwannoma. Clin Orthop Relat Res. 2004:69–73.Google Scholar
  16. 16.
    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.Google Scholar
  17. 17.
    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;66:1253–65.PubMedCrossRefGoogle Scholar
  18. 18.
    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;42:351–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Riad S, Biau D, Holt GE, Werier J, Turcotte RE, Ferguson PC, et al. The clinical and functional outcome for patients with radiation-induced soft tissue sarcoma. Cancer. 2012;118:2682–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Mavrogenis AF, Pala E, Guerra G, Ruggieri P. Post-radiation sarcomas. Clinical outcome of 52 Patients. J Surg Oncol. 2012;105:570–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Gladdy RA, Qin LX, Moraco N, Edgar MA, Antonescu CR, Alektiar KM, et al. Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? J Clin Oncol. 2010;28:2064–9.PubMedCrossRefGoogle Scholar
  22. 22.
    National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, USA, July 13–15, 1987. Neurofibromatosis. 1988;1:172–8.Google Scholar
  23. 23.
    Singer S, Maki RG, O’Sullivan B. Soft tissue sarcoma. In: DeVita VTJ, Lawrence TS, Rosenberg SA, et al., eds. Cancer: principles and practice of oncology, 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.Google Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Jennifer LaFemina
    • 1
  • Li-Xuan Qin
    • 2
  • Nicole H. Moraco
    • 1
  • Cristina R. Antonescu
    • 3
  • Ryan C. Fields
    • 1
  • Aimee M. Crago
    • 1
  • Murray F. Brennan
    • 1
  • Samuel Singer
    • 1
  1. 1.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations