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Published online: 2024-02-27

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Malignant peripheral nerve sheath tumor — from genetics to multidisciplinary treatment

Anna M. Czarnecka1, Paulina Chmiel1, Paweł Sobczuk1, Ewa Bartnik23, Mateusz Spałek14, Anna Szumera-Ciećkiewicz5, Marcin Zdzienicki1, Sławomir Falkowski1, Piotr Rutkowski1
DOI: 10.5603/ocp.98716

Abstract

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma (STS); it originates from nervous tissue and typically develops in proximity to nerve trunks in the limbs and trunk. These tumors, constituting approximately 5% of soft tissue sarcomas, can either form spontaneously or arise frompre-existing neurofibromas. The majority (90%) of cases occur in individuals between the 2nd and 5th decades of life. Themain risk factor for MPNST is von Recklinghausen disease (type 1 neurofibromatosis). The cornerstone of MPNST management involves radical surgicalmeasures, specifically tumor excision within healthy tissue boundaries (wide local excision), which is complemented by adjuvant radiotherapy. In case of metastatic disease, palliative chemotherapy employing doxorubicin or a combination of doxorubicin and ifosfamide is utilized. Approximately 25–30% of patients experience clinical improvement after chemotherapy. Looking ahead, advancements in research on molecular biology may lead to the development of inhibitors demonstrating greater efficacy than traditional chemotherapy for MPNST patients. At present, ongoing clinical trials of the therapeutic management of MPNST encompass pembrolizumab, the combination of nivolumab with ipilimumab, pexydartinib (an inhibitor targeting KIT, CSF1R, and FLT3) in conjunction with sirolimus, sapanisertib (a TORC1/2 inhibitor), or LOXO-195 (an inhibitor of neurotrophic tyrosine kinase receptors NTRK type 1, 2, and 3). 

Keywords: MPNSTmalignant peripheral nerve sheath tumorsarcomachemotherapyNF1

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References

  1. WHO Classification of Tumours Editorial Board. Soft Tissue and Bone Tumours. WHO Classification of Tumours, 5th Edition. World Health Organization 2013.
  2. Hirbe A, Gutmann D. The management of neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors: challenges, progress, and future prospects. Expert Opinion on Orphan Drugs. 2017; 5(8): 623–631.
    CrossRef
  3. Pala-Sadza A, Zajączkiewicz H, Banaś-Samson R, et al. Rzadki przypadek złośliwego nerwiaka osłonkowego jamy nosa. Polski Przegląd Otorynolaryngologiczny. 2014; 3(4): 210–213.
    CrossRef
  4. Boczej R, Walas R, Motyka M. Olbrzymi guz złośliwy nerwów obwodowych. Chirurgia Polska. 2013; 15(2): 141–145.
  5. De Raedt T, Brems H, Wolkenstein P, et al. Elevated risk for MPNST in NF1 microdeletion patients. Am J Hum Genet. 2003; 72(5): 1288–1292.
    CrossRefPubMed
  6. Evans DGR, Baser ME, McGaughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002; 39(5): 311–314.
    CrossRefPubMed
  7. Mackel CE, Medeiros I, Moore BE, et al. Intracranial Malignant Peripheral Nerve Sheath Tumors Not Associated with a Cranial Nerve: Systematic Review and Illustrative Case. World Neurosurg. 2021; 156: 76–91.
    CrossRefPubMed
  8. Miao R, Wang H, Jacobson A, et al. Radiation-induced and neurofibromatosis-associated malignant peripheral nerve sheath tumors (MPNST) have worse outcomes than sporadic MPNST. Radiother Oncol. 2019; 137: 61–70.
    CrossRefPubMed
  9. Farid M, Demicco EG, Garcia R, et al. Malignant peripheral nerve sheath tumors. Oncologist. 2014; 19(2): 193–201.
    CrossRefPubMed
  10. Shurell E, Tran LM, Nakashima J, et al. Gender dimorphism and age of onset in malignant peripheral nerve sheath tumor preclinical models and human patients. BMC Cancer. 2014; 14: 827.
    CrossRefPubMed
  11. Mowery A, Clayburgh D. Malignant peripheral nerve sheath tumors: Analysis of the national cancer database. Oral Oncol. 2019; 98: 13–19.
    CrossRefPubMed
  12. Brohl AS, Kahen E, Yoder SJ, et al. The genomic landscape of malignant peripheral nerve sheath tumors: diverse drivers of Ras pathway activation. Sci Rep. 2017; 7(1): 14992.
    CrossRefPubMed
  13. Brosseau JP, Le LuQ. Heterozygous Tumor Suppressor Microenvironment in Cancer Development. Trends Cancer. 2019; 5(9): 541–546.
    CrossRefPubMed
  14. Pemov A, Li H, Patidar R, et al. NISC Comparative Sequencing Program, NCI DCEG Cancer Genomics Research Laboratory. The primacy of NF1 loss as the driver of tumorigenesis in neurofibromatosis type 1-associated plexiform neurofibromas. Oncogene. 2017; 36(22): 3168–3177.
    CrossRefPubMed
  15. Messiaen LM, Callens T, Mortier G, et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000; 15(6): 541–555, doi: 10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N.
    PubMed
  16. Jadayel D, Fain P, Upadhyaya M, et al. Paternal origin of new mutations in Von Recklinghausen neurofibromatosis. Nature. 1990; 343(6258): 558–559.
    CrossRef
  17. Kahen EJ, Brohl A, Yu D, et al. Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors. Oncotarget. 2018; 9(32): 22571–22585.
    CrossRefPubMed
  18. Lee S, Rauch J, Kolch W. Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity. Int J Mol Sci. 2020; 21(3).
    CrossRefPubMed
  19. Zou Z, Tao T, Li H, et al. mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell & Bioscience. 2020; 10(1).
    CrossRef
  20. Watson AL, Keller BJ, Williams KA, et al. Correction: Co-targeting the MAPK and PI3K/AKT/mTOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity. Oncotarget. 2020; 11(39): 3618–3620.
    CrossRefPubMed
  21. Arshad T. A novel pan-RAS inhibitor for malignant peripheral nerve sheath tumors. J Clin Oncol. 2022; 40(16_suppl): e23531–e23531.
    CrossRef
  22. Endo M, Yamamoto H, Setsu N, et al. Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors. Clin Cancer Res. 2013; 19(2): 450–461.
    CrossRefPubMed
  23. Varin J, Poulain L, Hivelin M, et al. Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells. Oncotarget. 2016; 7(24): 35753–35767.
    CrossRefPubMed
  24. Zou CY, Smith KD, Zhu QS, et al. Dual targeting of AKT and mammalian target of rapamycin: a potential therapeutic approach for malignant peripheral nerve sheath tumor. Mol Cancer Ther. 2009; 8(5): 1157–1168.
    CrossRefPubMed
  25. Adnane L, Trail PA, Taylor I, et al. Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006; 407: 597–612.
    CrossRefPubMed
  26. Gudena V, Verma N, Post G, et al. Metastatic chest wall malignant schwannoma responding to sorafenib: case report and literature review. Cancer Biol Ther. 2008; 7(6): 810–813.
    CrossRefPubMed
  27. D'Adamo DR, Keohan ML, Carvajal RD, et al. A phase II trial of sorafenib (S) and dacarbazine (D) in leiomyosarcoma (LMS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumor (MPNST). J Clin Oncol. 2011; 29(15_suppl): 10025–10025.
    CrossRef
  28. Torres KE, Zhu QS, Bill K, et al. Activated MET is a molecular prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumors. Clin Cancer Res. 2011; 17(12): 3943–3955.
    CrossRefPubMed
  29. Jessen WJ, Miller SJ, Jousma E, et al. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest. 2013; 123(1): 340–347.
    CrossRefPubMed
  30. Fischer-Huchzermeyer S, Dombrowski A, Wilke G, et al. MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro. PLoS One. 2017; 12(11): e0187700.
    CrossRefPubMed
  31. Hitchen N, Cross M, Laking G, et al. Sporadic Metastatic Malignant Peripheral Nerve Sheath Tumour with an NF1 Mutation Responding to Trametinib: A Case Report. Case Rep Oncol. 2023; 16(1): 1–6.
    CrossRefPubMed
  32. Nagabushan S, Lau L, Barahona P, et al. Efficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor. npj Precision Oncology. 2021; 5(1).
    CrossRefPubMed
  33. Widemann BC, Lu Y, Reinke D, et al. Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016). Sarcoma. 2019; 2019: 7656747.
    CrossRefPubMed
  34. Kim A, Lu Y, Okuno SH, et al. Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023). Sarcoma. 2020; 2020: 5784876.
    CrossRefPubMed
  35. Peacock JD, Cherba D, Kampfschulte K, et al. Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors. J Transl Med. 2013; 11: 213.
    CrossRefPubMed
  36. Brosius S, Roth K, Carroll S. Combinatorial treatment of malignant peripheral nerve sheath tumors with tyrosine kinase inhibitors hinders proliferation and survival. The FASEB Journal. 2013; 27(S1).
    CrossRef
  37. Cichowski K, Shih TS, Schmitt E, et al. Mouse models of tumor development in neurofibromatosis type 1. Science. 1999; 286(5447): 2172–2176.
    CrossRefPubMed
  38. Yang FC, Ingram DA, Chen S, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow. Cell. 2008; 135(3): 437–448.
    CrossRefPubMed
  39. De Raedt T, Beert E, Pasmant E, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014; 514(7521): 247–251.
    CrossRefPubMed
  40. Legius E, Dierick H, Wu R, et al. TP53 mutations are frequent in malignant NF1 tumors. Genes Chromosomes Cancer. 1994; 10(4): 250–255.
    CrossRefPubMed
  41. Perry A, Kunz SN, Fuller CE, et al. Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms. J Neuropathol Exp Neurol. 2002; 61(8): 702–709.
    CrossRefPubMed
  42. Zhang M, Wang Y, Jones S, et al. Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet. 2014; 46(11): 1170–1172.
    CrossRefPubMed
  43. 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.
    CrossRefPubMed
  44. Thomas LE, Winston J, Rad E, et al. Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours. Hum Genomics. 2015; 9(1): 3.
    CrossRefPubMed
  45. Brekke HR, Ribeiro FR, Kolberg M, et al. Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group. J Clin Oncol. 2010; 28(9): 1573–1582.
    CrossRefPubMed
  46. Yang J, Du X. Genomic and molecular aberrations in malignant peripheral nerve sheath tumor and their roles in personalized target therapy. Surg Oncol. 2013; 22(3): e53–e57.
    CrossRefPubMed
  47. Skotheim RI, Kallioniemi A, Bjerkhagen B, et al. Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors and associated with clinical outcome. J Clin Oncol. 2003; 21(24): 4586–4591.
    CrossRefPubMed
  48. Amirnasr A, Verdijk RM, van Kuijk PF, et al. Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors. PLoS One. 2017; 12(8): e0183155.
    CrossRefPubMed
  49. Li H, Velasco-Miguel S, Vass WC, et al. Epidermal growth factor receptor signaling pathways are associated with tumorigenesis in the Nf1:p53 mouse tumor model. Cancer Res. 2002; 62(15): 4507–4513.
    PubMed
  50. Wu J, Patmore DM, Jousma E, et al. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors. Oncogene. 2014; 33(2): 173–180.
    CrossRefPubMed
  51. Albritton KH, Rankin C, Coffin CM, et al. Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST). J Clin Oncol. 2006; 24(18_suppl): 9518–9518.
    CrossRef
  52. Suppiah S, Mansouri S, Mamatjan Y, et al. Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities. Nat Commun. 2023; 14(1): 2696.
    CrossRefPubMed
  53. Amirnasr A, Verdijk RM, van Kuijk PF, et al. Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors. Sci Rep. 2020; 10(1): 2927.
    CrossRefPubMed
  54. Subramanian S, Thayanithy V, West RB, et al. Genome-wide transcriptome analyses reveal p53 inactivation mediated loss of miR-34a expression in malignant peripheral nerve sheath tumours. J Pathol. 2010; 220(1): 58–70.
    CrossRefPubMed
  55. Feber A, Wilson GA, Zhang Lu, et al. Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome Res. 2011; 21(4): 515–524.
    CrossRefPubMed
  56. Presneau N, Eskandarpour M, Shemais T, et al. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br J Cancer. 2013; 108(4): 964–972.
    CrossRefPubMed
  57. Röhrich M, Koelsche C, Schrimpf D, et al. Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol. 2016; 131(6): 877–887.
    CrossRefPubMed
  58. Cassier PA, Lefranc A, Amela EY, et al. A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group. Br J Cancer. 2013; 109(4): 909–914.
    CrossRefPubMed
  59. Seno N, Fukushima T, Gomi D, et al. Successful treatment with doxorubicin and ifosfamide for mediastinal malignant peripheral nerve sheath tumor with loss of H3K27me3 expression. Thorac Cancer. 2017; 8(6): 720–723.
    CrossRefPubMed
  60. Wassef M, Luscan A, Aflaki S, et al. EZH1/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer. Proc Natl Acad Sci U S A. 2019; 116(13): 6075–6080.
    CrossRefPubMed
  61. Katz D, Lazar A, Lev D. Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways. Expert Rev Mol Med. 2009; 11: e30.
    CrossRefPubMed
  62. Fukushima S, Endo M, Matsumoto Y, et al. Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor. PLoS One. 2017; 12(5): e0178064.
    CrossRefPubMed
  63. 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.
    CrossRefPubMed
  64. Lehnhardt M, Daigeler A, Homann HH, et al. [Importance of specialized centers in diagnosis and treatment of extremity-soft tissue sarcomas. Review of 603 cases]. Chirurg. 2009; 80(4): 341–347.
    CrossRefPubMed
  65. Sandrucci S, Trama A, Quagliuolo V, et al. Accreditation for centers of sarcoma surgery. Updates Surg. 2017; 69(1): 1–7.
    CrossRefPubMed
  66. Le Guellec S, Decouvelaere AV, Filleron T, et al. Malignant Peripheral Nerve Sheath Tumor Is a Challenging Diagnosis: A Systematic Pathology Review, Immunohistochemistry, and Molecular Analysis in 160 Patients From the French Sarcoma Group Database. Am J Surg Pathol. 2016; 40(7): 896–908.
    CrossRefPubMed
  67. Rodriguez FJ, Folpe AL, Giannini C, et al. Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol. 2012; 123(3): 295–319.
    CrossRefPubMed
  68. Kim A, Stewart DR, Reilly KM, et al. Malignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies. Sarcoma. 2017; 2017: 7429697.
    CrossRefPubMed
  69. Krawczyk MA, Karpinsky G, Izycka-Swieszewska E, et al. Immunohistochemical assessment of cyclin D1 and p53 is associated with survival in childhood malignant peripheral nerve sheath tumor. Cancer Biomark. 2019; 24(3): 351–361.
    CrossRefPubMed
  70. Zhou H, Coffin CM, Perkins SL, et al. Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions. Am J Surg Pathol. 2003; 27(10): 1337–1345.
    CrossRefPubMed
  71. Kamran SC, Howard SA, Shinagare AB, et al. Malignant peripheral nerve sheath tumors: prognostic impact of rhabdomyoblastic differentiation (malignant triton tumors), neurofibromatosis 1 status and location. Eur J Surg Oncol. 2013; 39(1): 46–52.
    CrossRefPubMed
  72. Mito JK, Qian X, Doyle LA, et al. Role of Histone H3K27 Trimethylation Loss as a Marker for Malignant Peripheral Nerve Sheath Tumor in Fine-Needle Aspiration and Small Biopsy Specimens. Am J Clin Pathol. 2017; 148(2): 179–189.
    CrossRefPubMed
  73. Ito Y, Kohashi K, Endo M, et al. Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation. Virchows Arch. 2021; 479(6): 1233–1244.
    CrossRefPubMed
  74. Wilson MP, Katlariwala P, Low G, et al. Diagnostic Accuracy of MRI for the Detection of Malignant Peripheral Nerve Sheath Tumors: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol. 2021; 217(1): 31–39.
    CrossRefPubMed
  75. Yun JS, Lee MH, Lee SM, et al. Peripheral nerve sheath tumor: differentiation of malignant from benign tumors with conventional and diffusion-weighted MRI. Eur Radiol. 2021; 31(3): 1548–1557.
    CrossRefPubMed
  76. Benz MR, Czernin J, Dry SM, et al. Quantitative F18-fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign. Cancer. 2010; 116(2): 451–458.
    CrossRefPubMed
  77. Nishida Y, Ikuta K, Ito S, et al. Limitations and benefits of FDG-PET/CT in NF1 patients with nerve sheath tumors: A cross-sectional/longitudinal study. Cancer Sci. 2021; 112(3): 1114–1122.
    CrossRefPubMed
  78. Assadi M, Velez E, Najafi MH, et al. PET Imaging of Peripheral Nerve Tumors. PET Clin. 2019; 14(1): 81–89.
    CrossRefPubMed
  79. Pendleton C, Howe BM, Spinner RJ. Percutaneous image-guided biopsy in malignant peripheral nerve sheath tumors. Acta Neurochir (Wien). 2021; 163(2): 515–519.
    CrossRefPubMed
  80. Pianta M, Chock E, Schlicht S, et al. Accuracy and complications of CT-guided core needle biopsy of peripheral nerve sheath tumours. Skeletal Radiol. 2015; 44(9): 1341–1349.
    CrossRefPubMed
  81. Graham DS, Russell TA, Eckardt MA, et al. Oncologic Accuracy of Image-guided Percutaneous Core-Needle Biopsy of Peripheral Nerve Sheath Tumors at a High-volume Sarcoma Center. Am J Clin Oncol. 2019; 42(10): 739–743.
    CrossRefPubMed
  82. Wakely PE, Ali SZ, Bishop JA. The cytopathology of malignant peripheral nerve sheath tumor: a report of 55 fine-needle aspiration cases. Cancer Cytopathol. 2012; 120(5): 334–341.
    CrossRefPubMed
  83. Tonsgard JH. Clinical manifestations and management of neurofibromatosis type 1. Semin Pediatr Neurol. 2006; 13(1): 2–7.
    CrossRefPubMed
  84. Evans DGR, Baser ME, McGaughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002; 39(5): 311–314.
    CrossRefPubMed
  85. Mautner VF, Asuagbor FA, Dombi E, et al. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008; 10(4): 593–598.
    CrossRefPubMed
  86. Derlin T, Tornquist K, Münster S, et al. Comparative effectiveness of 18F-FDG PET/CT versus whole-body MRI for detection of malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Clin Nucl Med. 2013; 38(1): e19–e25.
    CrossRefPubMed
  87. Well L, Salamon J, Kaul MG, et al. Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging. Neuro Oncol. 2019; 21(4): 508–516.
    CrossRefPubMed
  88. Baca N, Majlessipour F, Xie Y, et al. Characterization of pre-malignant lesions in patients with pediatric neurofibromatosis type 1 using a novel whole-body magnetic resonance imaging technique. J Clin Oncol. 2023; 41(16_suppl): TPS10637–TPS10637.
    CrossRef
  89. Ferner RE, Golding JF, Smith M, et al. [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol. 2008; 19(2): 390–394.
    CrossRefPubMed
  90. Salamon J, Veldhoen S, Apostolova I, et al. 18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off. Eur Radiol. 2014; 24(2): 405–412.
    CrossRefPubMed
  91. Chirindel A, Chaudhry M, Blakeley JO, et al. 18F-FDG PET/CT qualitative and quantitative evaluation in neurofibromatosis type 1 patients for detection of malignant transformation: comparison of early to delayed imaging with and without liver activity normalization. J Nucl Med. 2015; 56(3): 379–385.
    CrossRefPubMed
  92. Azizi AA, Slavc I, Theisen BE, et al. Monitoring of plexiform neurofibroma in children and adolescents with neurofibromatosis type 1 by [ F]FDG-PET imaging. Is it of value in asymptomatic patients? Pediatr Blood Cancer. 2018; 65(1).
    CrossRefPubMed
  93. Krzakowski M, Rutkowski P, Jassem J, et al. Zalecenia w zakresie zastosowania badań pozytonowej emisyjnej tomografii w onkologii. NOWOTWORY Journal of Oncology. 2011; 61(1): 57–69.
  94. Ahlawat S, Blakeley JO, Rodriguez FJ, et al. Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Neurology. 2019; 93(11): e1076–e1084.
    CrossRefPubMed
  95. Tovmassian D, Razak MA, London K. The Role of [18F]FDG-PET/CT in Predicting Malignant Transformation of Plexiform Neurofibromas in Neurofibromatosis-1. Int J Surg Oncol. 2016; 2016: 1–7.
    CrossRefPubMed
  96. Szymanski JJ, Sundby RT, Jones PA, et al. Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study. PLoS Med. 2021; 18(8): e1003734.
    CrossRefPubMed
  97. Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007; 44(2): 81–88.
    CrossRefPubMed
  98. Casali PG, Abecassis N, Bauer S, et al. Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4): iv51–iv67.
    CrossRefPubMed
  99. 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.
    CrossRefPubMed
  100. Higham CS, Steinberg SM, Dombi E, et al. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors. Sarcoma. 2017; 2017: 8685638.
    CrossRefPubMed
  101. Gronchi A, Stacchiotti S, Verderio P, et al. Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Ann Oncol. 2016; 27(12): 2283–2288.
    CrossRefPubMed
  102. Hirbe AC, Cosper PF, Dahiya S, et al. Neoadjuvant Ifosfamide and Epirubicin in the Treatment of Malignant Peripheral Nerve Sheath Tumors. Sarcoma. 2017; 2017: 3761292.
    CrossRefPubMed
  103. Gronchi A, Ferrari S, Quagliuolo V, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017; 18(6): 812–822.
    CrossRefPubMed
  104. Gronchi A, Palmerini E, Quagliuolo V, et al. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020; 38(19): 2178–2186.
    CrossRefPubMed
  105. Karpinsky G, Krawczyk MA, Izycka-Swieszewska E, et al. Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor. J Cancer Res Clin Oncol. 2018; 144(3): 519–529.
    CrossRefPubMed
  106. Weiss A, Chen YL, Scharschmidt T, et al. Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2020; 21(8): 1110–1122.
    CrossRefPubMed
  107. Shurell-Linehan E, DiPardo BJ, Elliott IA, et al. Pathologic Response to Neoadjuvant Therapy is Associated With Improved Long-term Survival in High-risk Primary Localized Malignant Peripheral Nerve Sheath Tumors. Am J Clin Oncol. 2019; 42(5): 426–431.
    CrossRefPubMed
  108. Valentin T, Le Cesne A, Ray-Coquard I, et al. Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO). Eur J Cancer. 2016; 56: 77–84.
    CrossRefPubMed
  109. Hwang InK, Hahn SM, Kim HS, et al. Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1. Cancer Res Treat. 2017; 49(3): 717–726.
    CrossRefPubMed
  110. Longhi A, Errani C, Magagnoli G, et al. High grade malignant peripheral nerve sheath tumors: outcome of 62 patients with localized disease and review of the literature. J Chemother. 2010; 22(6): 413–418.
    CrossRefPubMed
  111. Bishop AJ, Zagars GK, Torres KE, et al. Malignant Peripheral Nerve Sheath Tumors: A Single Institution's Experience Using Combined Surgery and Radiation Therapy. Am J Clin Oncol. 2018; 41(5): 465–470.
    CrossRefPubMed
  112. Stucky CC, Johnson K, Gray R, et al. Malignant Peripheral Nerve Sheath Tumors (MPNST): The Mayo Clinic Experience. Ann Surg Oncol. 2011; 19(3): 878–885.
    CrossRefPubMed
  113. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008; 113(3): 573–581.
    CrossRefPubMed
  114. Anghileri M, Miceli R, Fiore M, et al. Malignant peripheral nerve sheath tumors. Cancer. 2006; 107(5): 1065–1074.
    CrossRefPubMed
  115. Wong WW, Hirose T, Scheithauer BW, et al. Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys. 1998; 42(2): 351–360.
    CrossRefPubMed
  116. DeLaney TF, Liebsch NJ, Pedlow FX, et al. Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014; 110(2): 115–122.
    CrossRefPubMed
  117. Jensen AD, Uhl M, Chaudhri N, et al. Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome. Radiat Oncol. 2015; 10: 109.
    CrossRefPubMed
  118. Voth C, Wu X, Keirns D, et al. Analysis of demographic characteristics of malignant peripheral nerve sheath tumor in adults: A National Cancer Database study. J Clin Oncol. 2023; 41(16_suppl): e23555–e23555.
    CrossRef
  119. 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.
    CrossRefPubMed
  120. Kolberg M, Høland M, Agesen TH, et al. Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro Oncol. 2013; 15(2): 135–147.
    CrossRefPubMed
  121. Hirozane T, Nakayama R, Yamaguchi S, et al. Recurrent malignant peripheral nerve sheath tumor presenting as an asymptomatic intravenous thrombus extending to the heart: a case report. World J Surg Oncol. 2022; 20(1): 8.
    CrossRefPubMed
  122. Lee CS, Huh JiS, Chang JW, et al. The early detection of recurrence of malignant peripheral nerve sheath tumor by frequent magnetic resonance imaging. J Korean Neurosurg Soc. 2010; 47(1): 51–54.
    CrossRefPubMed
  123. Marickar YM, Abraham B. Malignant peripheral nerve sheath tumour - A long story: Case report. Int J Surg Case Rep. 2020; 77: 618–623.
    CrossRefPubMed
  124. Gronchi A, Miah AB, Tos APD, et al. Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021; 32(11): 1348–1365.
    CrossRefPubMed
  125. Kahn J, Gillespie A, Ondos J, et al. Radiation Therapy in Management of Sporadic and Neurofibromatosis Type 1 (NF1) Associated Malignant Peripheral Nerve Sheath Tumors (MPNST). International Journal of Radiation Oncology*Biology*Physics. 2012; 84(3): S638.
    CrossRef
  126. Boyce-Fappiano D, Damron EP, Farooqi A, et al. Hypofractionated Radiation Therapy for Unresectable or Metastatic Sarcoma Lesions. Adv Radiat Oncol. 2022; 7(3): 100913.
    CrossRefPubMed
  127. 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. 2011; 22(1): 207–214.
    CrossRefPubMed
  128. Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995; 13(7): 1537–1545.
    CrossRefPubMed
  129. Judson I, Verweij J, Gelderblom H, et al. European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014; 15(4): 415–423.
    CrossRefPubMed
  130. Zehou O, Fabre E, Zelek L, 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.
    CrossRefPubMed
  131. Torres KE, Liu J, Young E, et al. Expression of 'drugable' tyrosine kinase receptors in malignant peripheral nerve sheath tumour: potential molecular therapeutic targets for a chemoresistant cancer. Histopathology. 2011; 59(1): 156–159.
    CrossRefPubMed
  132. Tawbi H, Thomas D, Lucas DR, et al. Epidermal growth factor receptor expression and mutational analysis in synovial sarcomas and malignant peripheral nerve sheath tumors. Oncologist. 2008; 13(4): 459–466.
    CrossRefPubMed
  133. Albritton KH, Rankin C, Coffin CM, et al. Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST). J Clin Oncol. 2006; 24(18_suppl): 9518–9518.
    CrossRef
  134. Widemann B, Meyer C, Cote G, et al. SARC016: Phase II study of everolimus in combination with bevacizumab in sporadic and neurofibromatosis type 1 (NF1) related refractory malignant peripheral nerve sheath tumors (MPNST). J Clin Oncol. 2016; 34(15_suppl): 11053–11053.
    CrossRef
  135. Kim A, Reinke D, Cichowski K, et al. SARC023: Phase I/II trial of ganetespib in combination with sirolimus for refractory sarcomas and malignant peripheral nerve sheath tumors (MPNST). J Clin Oncol. 2014; 32(15_suppl): TPS10603–TPS10603.
    CrossRef
  136. Chugh R, Wathen JK, Maki RG, et al. Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol. 2009; 27(19): 3148–3153.
    CrossRefPubMed
  137. Maki RG, D'Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009; 27(19): 3133–3140.
    CrossRefPubMed
  138. Akshintala S, Mallory N, Lu Y, et al. Outcome of patients with refractory malignant peripheral nerve sheath tumors (MPNST) enrolled on phase 2 trials. J Clin Oncol. 2019; 37(15_suppl): e22534–e22534.
    CrossRef
  139. Manji G, Patwardhan P, Lee S, et al. Phase 1/2 study of combination therapy with pexidartinib and sirolimus to target tumor-associated macrophages in malignant peripheral nerve sheath tumors. J Clin Oncol. 2016; 34(15_suppl): TPS11070–TPS11070.
    CrossRef
  140. Manji GA, Van Tine BA, Lee SM, et al. A Phase I Study of the Combination of Pexidartinib and Sirolimus to Target Tumor-Associated Macrophages in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors. Clin Cancer Res. 2021; 27(20): 5519–5527.
    CrossRefPubMed
  141. Davis L, Latour E, Burch R, et al. A phase Ib study of ribociclib in combination with doxorubicin in advanced soft tissue sarcomas (aSTS). J Clin Oncol. 2020; 38(15_suppl): 11548–11548.
    CrossRef
  142. Striefler JK, Brandes F, Baur A, et al. Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience. BMC Cancer. 2020; 20(1): 68.
    CrossRefPubMed
  143. Tap WD, Wagner AJ, Schöffski P, et al. ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020; 323(13): 1266–1276.
    CrossRefPubMed
  144. Hyman D, Kummar S, Farago A, et al. Abstract CT127: Phase I and expanded access experience of LOXO-195 (BAY 2731954), a selective next-generation TRK inhibitor (TRKi). Cancer Res. 2019; 79(13_Supplement): CT127–CT127.
    CrossRef
  145. Yoo KH, Kim HS, Lee SuJ, et al. Efficacy of pazopanib monotherapy in patients who had been heavily pretreated for metastatic soft tissue sarcoma: a retrospective case series. BMC Cancer. 2015; 15: 154.
    CrossRefPubMed
  146. Nakamura T, Matsumine A, Kawai A, et al. The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study. Cancer. 2016; 122(9): 1408–1416.
    CrossRefPubMed
  147. Nishida Y, Urakawa H, Nakayama R, et al. Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. Int J Cancer. 2020; 148(1): 140–149.
    CrossRefPubMed
  148. Ryan C, Degnin C, Cranmer L, et al. A randomized phase II study of gemcitabine (G) alone or with pazopanib (P) in refractory soft tissue sarcoma (STS). J Clin Oncol. 2020; 38(15_suppl): 11515–11515.
    CrossRef
  149. Ingham M, Mahoney M, Remotti F, et al. A randomized phase II study of MLN0128 (M) versus pazopanib (P) in patients (pt) with advanced sarcoma (Alliance A091304). J Clin Oncol. 2020; 38(15_suppl): 11562–11562.
    CrossRef
  150. CT02601209. Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma. December 2023. https://clinicaltrials.gov/study/NCT02601209.
  151. Patel SP, Othus M, Chae YK, et al. A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors. Clin Cancer Res. 2020; 26(10): 2290–2296.
    CrossRefPubMed
  152. Movva S, Avutu V, Chi P, et al. A pilot study of lenvatinib plus pembrolizumab in patients with advanced sarcoma. J Clin Oncol. 2023; 41(16_suppl): 11517–11517.
    CrossRef
  153. Somaiah N, Tine BV, Chmielowski B, et al. A phase 2 study of alrizomadlin, a novel MDM2/p53 inhibitor, in combination with pembrolizumab for treatment of patients with malignant peripheral nerve sheath tumor (MPNST). J Clin Oncol. 2023; 41(16_suppl): e14627–e14627.
    CrossRef
  154. Yan P, Huang R, Hu P, et al. Nomograms for predicting the overall and cause-specific survival in patients with malignant peripheral nerve sheath tumor: a population-based study. J Neurooncol. 2019; 143(3): 495–503.
    CrossRefPubMed
  155. 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.
    CrossRefPubMed
  156. 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.
    CrossRefPubMed
  157. Wakeman KM, Zhang QS, Bandhlish A, et al. Fédération Nationale Des Centres de Lutte Contre Le Cancer (FNCLCC) Grading, Margin Status and Tumor Location Associate With Survival Outcomes in Malignant Peripheral Nerve Sheath Tumors. Am J Clin Oncol. 2022; 45(1): 28–35.
    CrossRefPubMed
  158. Martin E, Muskens IS, Coert JH, et al. Treatment and survival differences across tumor sites in malignant peripheral nerve sheath tumors: a SEER database analysis and review of the literature. Neurooncol Pract. 2019; 6(2): 134–143.
    CrossRefPubMed
  159. Kromer CM, Yacoub N, Xiong D, et al. Analysis of Survival Differences Between Cutaneous and Subcutaneous Malignant Peripheral Nerve Sheath Tumors. Dermatol Surg. 2023; 49(4): 322–329.
    CrossRefPubMed
  160. Xu Y, Xu G, Liu Z, et al. Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors. Acta Neurochir (Wien). 2021; 163(2): 521–529.
    CrossRefPubMed
  161. Sobczuk P, Teterycz P, Zdzienicki M, et al. Clinicopathological prognostic and predictive factors of malignant peripheral nerve sheath tumors (MPNST) survival and treatment efficacy. J Clin Oncol. 2019; 37(15_suppl): e22537–e22537.
    CrossRef
  162. Porter DE, Prasad V, Foster L, et al. Survival in Malignant Peripheral Nerve Sheath Tumours: A Comparison between Sporadic and Neurofibromatosis Type 1-Associated Tumours. Sarcoma. 2009; 2009: 756395.
    CrossRefPubMed
  163. Malbari F, Spira M, B Knight P, et al. Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis: Impact of Family History. J Pediatr Hematol Oncol. 2018; 40(6): e359–e363.
    CrossRefPubMed
  164. Cai Z, Tang X, Liang H, et al. Prognosis and risk factors for malignant peripheral nerve sheath tumor: a systematic review and meta-analysis. World J Surg Oncol. 2020; 18(1): 257.
    CrossRefPubMed
  165. Martin E, Coert JH, Flucke UE, et al. Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study. Pediatr Blood Cancer. 2020; 67(4): e28138.
    CrossRefPubMed
  166. van Noesel MM, Orbach D, Brennan B, et al. Outcome and prognostic factors in pediatric malignant peripheral nerve sheath tumors: An analysis of the European Pediatric Soft Tissue Sarcoma Group (EpSSG) NRSTS-2005 prospective study. Pediatr Blood Cancer. 2019; 66(10): e27833.
    CrossRefPubMed
  167. Bartlett EK, Sharma A, Seier K, et al. Histology-Specific Prognostication for Radiation-Associated Soft Tissue Sarcoma. JCO Precis Oncol. 2022; 6: e2200087.
    CrossRefPubMed
  168. 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.
    CrossRefPubMed
  169. 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.
    CrossRefPubMed

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