Top

Child's Nervous System

Published in:

Open Access 01-10-2020 | Radiotherapy | Special Annual Issue

Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease

Authors: Enrico Martin, Uta E. Flucke, J. Henk Coert, Max M. van Noesel

Published in: Child's Nervous System | Issue 10/2020

Abstract

Background

Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients.

Methods

This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients.

Results

Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment.

Conclusion

Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.

Basu TN, Gutmann DH, Fletcher JA, Glover TW, Collins FS, Downward J (1992) Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature 356:713–715. https://doi.org/10.1038/356713a0CrossRefPubMed

Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM (1986) Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 57:2006–2021CrossRef

Evans DGR, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (2002) Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 39:311–314CrossRef

Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, Hamel MJ, Martin L, Barbarot S, Leheup B, Rodriguez D, Lacombe D, Dollfus H, Pasquier L, Isidor B, Ferkal S, Soulier J, Sanson M, Dieux-Coeslier A, Bièche I, Parfait B, Vidaud M, Wolkenstein P, Upadhyaya M, Vidaud D, members of the NF France Network (2010) NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat 31:E1506–E1518. https://doi.org/10.1002/humu.21271CrossRefPubMed

Evans DGR, Huson SM, Birch JM (2012) Malignant peripheral nerve sheath tumours in inherited disease. Clin Sarcoma Res 2:17. https://doi.org/10.1186/2045-3329-2-17CrossRefPubMedPubMedCentral

Ng VY, Scharschmidt TJ, Mayerson JL, Fisher JL (2013) Incidence and survival in sarcoma in the United States: a focus on musculoskeletal lesions. Anticancer Res 33:2597–2604PubMed

Martin E, Muskens IS, Coert JH et al (2018) Treatment and survival differences across tumor sites in malignant peripheral nerve sheath tumors: a SEER database analysis. Neuro-Oncology Pract:1–10

Martin E, Coert JH, Flucke UE, Slooff WBM, de Sande MAJ, Noesel MM, Grünhagen DJ, Wijnen MHWA, Verhoef C (2019) Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: a nationwide cohort study. Pediatr Blood Cancer 67:e28138. https://doi.org/10.1002/pbc.28138CrossRefPubMed

Ferrari A, Miceli R, Rey A, Oberlin O, Orbach D, Brennan B, Mariani L, Carli M, Bisogno G, Cecchetto G, Salvo GLD, Casanova M, Vannoesel MM, Kelsey A, Stevens MC, Devidas M, Pappo AS, Spunt SL (2011) Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47:724–731. https://doi.org/10.1016/j.ejca.2010.11.013CrossRefPubMed

10.

Zou C, Smith KD, Liu J, Lahat G, Myers S, Wang WL, Zhang W, McCutcheon IE, Slopis JM, Lazar AJ, Pollock RE, Lev D (2009) Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg 249:1014–1022. https://doi.org/10.1097/SLA.0b013e3181a77e9aCrossRefPubMed

11.

Stucky C-CH, Johnson KN, Gray RJ, Pockaj BA, Ocal IT, Rose PS, Wasif N (2012) Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Ann Surg Oncol 19:878–885. https://doi.org/10.1245/s10434-011-1978-7CrossRefPubMed

12.

Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, Lozza L, Collini P, Olmi P, Casali PG, Pilotti S, Gronchi A (2006) Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer 107:1065–1074. https://doi.org/10.1002/cncr.22098CrossRefPubMed

13.

Valentin T, Le Cesne A, Ray-Coquard I et al (2016) Management and prognosis of malignant peripheral nerve sheath tumors: the experience of the French Sarcoma Group (GSF-GETO). Eur J Cancer 56:77–84. https://doi.org/10.1016/j.ejca.2015.12.015CrossRefPubMed

14.

Miao R, Wang H, Jacobson A, Lietz AP, Choy E, Raskin KA, Schwab JH, Deshpande V, Nielsen GP, DeLaney TF, Cote GM, Hornicek FJ, Chen YLE (2019) Radiation-induced and neurofibromatosis-associated malignant peripheral nerve sheath tumors (MPNST) have worse outcomes than sporadic MPNST. Radiother Oncol 137:61–70. https://doi.org/10.1016/j.radonc.2019.03.015CrossRefPubMed

15.

Martin E, Coert JH, Flucke UE, Slooff WBM, Ho VKY, van der Graaf WT, van Dalen T, van de Sande MAJ, van Houdt WJ, Grünhagen DJ, Verhoef C (2019) A nationwide cohort study on treatment and survival in patients with malignant peripheral nerve sheath tumours. Eur J Cancer 124:77–87. https://doi.org/10.1016/j.ejca.2019.10.014CrossRefPubMed

16.

Eisenbarth I, Beyer K, Krone W, Assum G (2000) Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1. Am J Hum Genet 66:393–401. https://doi.org/10.1086/302747CrossRefPubMedPubMedCentral

17.

Endo M, Yamamoto H, Setsu N, Kohashi K, Takahashi Y, Ishii T, Iida KI, Matsumoto Y, Hakozaki M, Aoki M, Iwasaki H, Dobashi Y, Nishiyama K, Iwamoto Y, Oda Y (2013) 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 19:450–461. https://doi.org/10.1158/1078-0432.CCR-12-1067CrossRefPubMed

18.

Kluwe L, Friedrich RE, Mautner VF (1999) Allelic loss of the NF1 gene in NF1-associated plexiform neurofibromas. Cancer Genet Cytogenet 113:65–69CrossRef

19.

Beert E, Brems H, Daniels B et al (2011) Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosom Cancer 50:1021–1032. https://doi.org/10.1002/gcc.20921CrossRefPubMed

20.

De Raedt T, Beert E, Pasmant E et al (2014) PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 514:247–251. https://doi.org/10.1038/nature13561CrossRefPubMed

21.

Legius E, Dierick H, Wu R, Hall BK, Marynen P, Cassiman JJ, Glover TW (1994) TP53 mutations are frequent in malignant NF1 tumors. Genes Chromosom Cancer 10:250–255CrossRef

22.

Masliah-Planchon J, Pasmant E, Luscan A, Laurendeau I, Ortonne N, Hivelin M, Varin J, Valeyrie-Allanore L, Dumaine V, Lantieri L, Leroy K, Parfait B, Wolkenstein P, Vidaud M, Vidaud D, Bièche I (2013) MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis. BMC Genomics 14:473. https://doi.org/10.1186/1471-2164-14-473CrossRefPubMedPubMedCentral

23.

Upadhyaya M, Spurlock G, Thomas L, Thomas NST, Richards M, Mautner VF, Cooper DN, Guha A, Yan J (2012) Microarray-based copy number analysis of neurofibromatosis type-1 (NF1)-associated malignant peripheral nerve sheath tumors reveals a role for Rho-GTPase pathway genes in NF1 tumorigenesis. Hum Mutat 33:763–776. https://doi.org/10.1002/humu.22044CrossRefPubMed

24.

Zhang M, Wang Y, Jones S, Sausen M, McMahon K, Sharma R, Wang Q, Belzberg AJ, Chaichana K, Gallia GL, Gokaslan ZL, Riggins GJ, Wolinksy JP, Wood LD, Montgomery EA, Hruban RH, Kinzler KW, Papadopoulos N, Vogelstein B, Bettegowda C (2014) Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet 46:1170–1172. https://doi.org/10.1038/ng.3116CrossRefPubMedPubMedCentral

25.

Carli M, Ferrari A, Mattke A, Zanetti I, Casanova M, Bisogno G, Cecchetto G, Alaggio R, de Sio L, Koscielniak E, Sotti G, Treuner J (2005) Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23:8422–8430. https://doi.org/10.1200/JCO.2005.01.4886CrossRefPubMed

26.

Pratt CB, Maurer HM, Gieser P, Salzberg A, Rao BN, Parham D, Thomas PRM, Marcus RB, Cantor A, Pick T, Green D, Neff J, Jenkins JJ (1998) Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30:201–209CrossRef

27.

Spunt SL, Hill DA, Motosue AM, Billups CA, Cain AM, Rao BN, Pratt CB, Merchant TE, Pappo AS (2002) Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Clin Oncol 20:3225–3235. https://doi.org/10.1200/JCO.2002.06.066CrossRefPubMed

28.

Ferrari A, Casanova M, Collini P, Meazza C, Luksch R, Massimino M, Cefalo G, Terenziani M, Spreafico F, Catania S, Gandola L, Gronchi A, Mariani L, Fossati-Bellani F (2005) Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23:4021–4030. https://doi.org/10.1200/JCO.2005.02.053CrossRefPubMed

29.

van Noesel MM, Orbach D, Brennan B, Kelsey A, Zanetti I, de Salvo GL, Gaze MN, Craigie RJ, McHugh K, Francotte N, Collini P, Bisogno G, Casanova M, Ferrari A (2019) 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 66:e27833. https://doi.org/10.1002/pbc.27833CrossRefPubMed

30.

Kolberg M, Holand M, Agesen TH, Brekke HR, Liestol K, Hall KS, Mertens F, Picci P, Smeland S, Lothe RA (2013) Survival meta-analyses for >1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1. Neuro-Oncology 15:135–147. https://doi.org/10.1093/neuonc/nos287CrossRefPubMed

31.

Meis JM, Enzinger FM, Martz KL, Neal JA (1992) Malignant peripheral nerve sheath tumors (malignant schwannomas) in children. Am J Surg Pathol 16:694–707CrossRef

32.

Upadhyaya M, Osborn MJ, Maynard J, Kim MR, Tamanoi F, Cooper DN (1997) Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene. Hum Genet 99:88–92. https://doi.org/10.1007/s004390050317CrossRefPubMed

33.

Lee W, Teckie S, Wiesner T, Ran L, Prieto Granada CN, Lin M, Zhu S, Cao Z, Liang Y, Sboner A, Tap WD, Fletcher JA, Huberman KH, Qin LX, Viale A, Singer S, Zheng D, Berger MF, Chen Y, Antonescu CR, Chi P (2014) PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet 46:1227–1232. https://doi.org/10.1038/ng.3095CrossRefPubMedPubMedCentral

34.

S.L. C (2016) 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 186:464–477 . doi: 10.1016/j.ajpath.2015.10.023LK - http://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=15252191&id=doi:10.1016%2Fj.ajpath.2015.10.023&atitle=The+challenge+of+cancer+genomics+in+rare+nervous+system+neoplasms%3A+Malignant+peripheral+nerve+sheath+tumors+as+a+paradigm+for+cross-species+comparative+oncogenomics&stitle=Am.+J.+Pathol.&title=American+Journal+of+Pathology&volume=186&issue=3&spage=464&epage=477&aulast=Carroll&aufirst=Steven+L.&auinit=S.L.&aufull=Carroll+S.L.&coden=AJPAA&isbn=&pages=464-477&d

35.

Goldblum J, Weiss S, Folpe AL (2019) Enzinger and Weiss’s Soft Tissue Tumor, 7th Editio. Elsevier Ltd

36.

Le Guellec S, Decouvelaere A-V, Filleron T et al (2016) 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 40:896–908. https://doi.org/10.1097/PAS.0000000000000655CrossRefPubMed

37.

Rodriguez FJ, Folpe AL, Giannini C, Perry A (2012) Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 123:295–319. https://doi.org/10.1007/s00401-012-0954-zCrossRefPubMedPubMedCentral

38.

Martinez AP, Fritchie KJ (2019) Update on peripheral nerve sheath tumors. Surg Pathol Clin 12:1–19. https://doi.org/10.1016/j.path.2018.10.001CrossRefPubMed

39.

Röhrich M, Koelsche C, Schrimpf D, Capper D, Sahm F, Kratz A, Reuss J, Hovestadt V, Jones DTW, Bewerunge-Hudler M, Becker A, Weis J, Mawrin C, Mittelbronn M, Perry A, Mautner VF, Mechtersheimer G, Hartmann C, Okuducu AF, Arp M, Seiz-Rosenhagen M, Hänggi D, Heim S, Paulus W, Schittenhelm J, Ahmadi R, Herold-Mende C, Unterberg A, Pfister SM, von Deimling A, Reuss DE (2016) Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol 131:877–887. https://doi.org/10.1007/s00401-016-1540-6CrossRefPubMed

40.

Wasa J, Nishida Y, Tsukushi S, Shido Y, Sugiura H, Nakashima H, Ishiguro N (2010) MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. Am J Roentgenol 194:1568–1574. https://doi.org/10.2214/AJR.09.2724CrossRef

41.

Ferner RE (2007) Neurofibromatosis 1. Eur J Hum Genet 15:131–138. https://doi.org/10.1038/sj.ejhg.5201676LKhttp://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=10184813&id=doi:10.1038%2Fsj.ejhg.5201676&atitle=Neurofibromatosis+1&stitle=Eur.+J.+Hum.+Genet.&title=European+Journal+of+Human+Genetics&volume=15&issue=2&spage=131&epage=138&aulast=Ferner&aufirst=Rosalie+E.&auinit=R.E.&aufull=Ferner+R.E.&coden=EJHGE&isbn=&pages=131-138&date=2007&auinit1=R&auinitm=ECrossRefPubMed

42.

Perez-Roman RJ, Shelby Burks S, Debs L, Cajigas I, Levi AD (2020) The risk of peripheral nerve tumor biopsy in suspected benign etiologies. Neurosurgery. 86:E326–E332. https://doi.org/10.1093/neuros/nyz549CrossRefPubMed

43.

Graham DS, Russell TA, Eckardt MA, Motamedi K, Seeger LL, Singh AS, Bernthal NM, Kalbasi A, Dry SM, Nelson SD, Elashoff D, Levine BD, Eilber FC (2019) Oncologic accuracy of image-guided percutaneous core-needle biopsy of peripheral nerve sheath tumors at a high-volume sarcoma center. Am J Clin Oncol 42:739–743. https://doi.org/10.1097/COC.0000000000000591CrossRefPubMed

44.

Spurlock G, Knight SJL, Thomas N, Kiehl TR, Guha A, Upadhyaya M (2010) Molecular evolution of a neurofibroma to malignant peripheral nerve sheath tumor (MPNST) in an NF1 patient: correlation between histopathological, clinical and molecular findings. J Cancer Res Clin Oncol 136:1869–1880. https://doi.org/10.1007/s00432-010-0846-3CrossRefPubMed

45.

Derlin T, Tornquist K, Munster S et al (2013) 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 38:e19–e25. https://doi.org/10.1097/RLU.0b013e318266ce84CrossRefPubMed

46.

Reinert CP, Schuhmann MU, Bender B, Gugel I, la Fougère C, Schäfer J, Gatidis S (2019) Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI. Eur J Nucl Med Mol Imaging 46:776–787. https://doi.org/10.1007/s00259-018-4227-5CrossRefPubMed

47.

Bhargava R, Parham DM, Lasater OE, Chari RS, Chen G, Fletcher BD (1997) MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign. Pediatr Radiol 27:124–129. https://doi.org/10.1007/s002470050082CrossRefPubMed

48.

Ferner RE, Golding JF, Smith M, Calonje E, Jan W, Sanjayanathan V, O’Doherty M (2008) [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 19:390–394. https://doi.org/10.1093/annonc/mdm450CrossRefPubMed

49.

Warbey VS, Ferner RE, Dunn JT, Calonje E, O’Doherty MJ (2009) [18F] FDG PET/CT in the diagnosis of malignant peripheral nerve sheath tumours in neurofibromatosis type-1. Eur J Nucl Med Mol Imaging 36:751–757. https://doi.org/10.1007/s00259-008-1038-0CrossRefPubMed

50.

Ahlawat S, Blakeley JO, Rodriguez FJ, Fayad LM (2019) Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Neurology 93:e1076–e1084. https://doi.org/10.1212/WNL.0000000000008092CrossRefPubMed

51.

Broski SM, Johnson GB, Howe BM, Nathan MA, Wenger DE, Spinner RJ, Amrami KK (2016) Evaluation of 18F-FDG PET and MRI in differentiating benign and malignant peripheral nerve sheath tumors. Skelet Radiol 45:1097–1105. https://doi.org/10.1007/s00256-016-2394-7CrossRef

52.

Salamon J, Veldhoen S, Apostolova I, Bannas P, Yamamura J, Herrmann J, Friedrich RE, Adam G, Mautner VF, Derlin T (2014) F-18-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 24:405–412. https://doi.org/10.1007/s00330-013-3020-xCrossRefPubMed

53.

Schwabe M, Spiridonov S, Yanik EL, Jennings JW, Hillen T, Ponisio M, McDonald DJ, Dehdashti F, Cipriano CA (2019) How effective are noninvasive tests for diagnosing malignant peripheral nerve sheath tumors in patients with neurofibromatosis type 1? Diagnosing MPNST in NF1 patients. Sarcoma 2019:4627521–4627528. https://doi.org/10.1155/2019/4627521CrossRefPubMedPubMedCentral

54.

Combemale P, Valeyrie-Allanore L, Giammarile F, Pinson S, Guillot B, Goulart DM, Wolkenstein P, Blay JY, Mognetti T (2014) Utility of 18F-FDG PET with a semi-quantitative index in the detection of sarcomatous transformation in patients with neurofibromatosis type 1. PLoS One 9:e85954. https://doi.org/10.1371/journal.pone.0085954CrossRefPubMedPubMedCentral

55.

Cook GJR, Lovat E, Siddique M, Goh V, Ferner R, Warbey VS (2017) Characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 using heterogeneity analysis of (18)F-FDG PET. Eur J Nucl Med Mol Imaging 44:1845–1852. https://doi.org/10.1007/s00259-017-3733-1CrossRefPubMedPubMedCentral

56.

Well L, Salamon J, Kaul MG, Farschtschi S, Herrmann J, Geier KI, Hagel C, Bockhorn M, Bannas P, Adam G, Mautner VF, Derlin T (2019) Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging. Neuro-Oncology 21:508–516. https://doi.org/10.1093/neuonc/noy199CrossRefPubMed

57.

Sauter ER (2017) Reliable biomarkers to identify new and recurrent cancer. Eur J breast Heal 13:162–167. https://doi.org/10.5152/ejbh.2017.3635CrossRef

58.

Frankel S, Smith GD, Donovan J, Neal D (2003) Screening for prostate cancer. Lancet (London, England) 361:1122–1128 https://doi.org/10.1016/S0140-6736(03)12890-5

59.

Chu GCW, Lazare K, Sullivan F (2018) Serum and blood based biomarkers for lung cancer screening: a systematic review. BMC Cancer 18:181. https://doi.org/10.1186/s12885-018-4024-3CrossRefPubMedPubMedCentral

60.

Hummel TR, Jessen WJ, Miller SJ, Kluwe L, Mautner VF, Wallace MR, Lazaro C, Page GP, Worley PF, Aronow BJ, Schorry EK, Ratner N (2010) Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin Cancer Res 16:5048–5057. https://doi.org/10.1158/1078-0432.CCR-10-0613CrossRefPubMedPubMedCentral

61.

Johansson G, Peng P-C, Huang P-Y, Chien HF, Hua KT, Kuo ML, Chen CT, Lee MJ (2014) Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden. PLoS One 9:e115916. https://doi.org/10.1371/journal.pone.0115916CrossRefPubMedPubMedCentral

62.

Park S-J, Sawitzki B, Kluwe L, Mautner VF, Holtkamp N, Kurtz A (2013) Serum biomarkers for neurofibromatosis type 1 and early detection of malignant peripheral nerve-sheath tumors. BMC Med 11:109. https://doi.org/10.1186/1741-7015-11-109CrossRefPubMedPubMedCentral

63.

Watson KL, Al Sannaa GA, Kivlin CM et al (2017) Patterns of recurrence and survival in sporadic, neurofibromatosis type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors. J Neurosurg 126:319–329. https://doi.org/10.3171/2015.12.JNS152443CrossRefPubMed

64.

Puffer RC, Graffeo CS, Mallory GW et al (2016) Brain metastasis from malignant peripheral nerve sheath tumors. World Neurosurg 92:580.e1–580.e4. https://doi.org/10.1016/j.wneu.2016.06.069CrossRef

65.

Casali PG, Abecassis N, Aro HT et al (2018) Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol 29:iv51–iv67. https://doi.org/10.1093/annonc/mdy096CrossRef

66.

Ferner RE, Gutmann DH (2002) International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res 62:1573–1577PubMed

67.

Nelson CN, Dombi E, Rosenblum JS, Miettinen MM, Lehky TJ, Whitcomb PO, Hayes C, Scott G, Benzo S, Widemann BC, Chittiboina P (2019) Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1. J Neurosurg:1–11. https://doi.org/10.3171/2019.7.JNS191353

68.

Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL (1998) Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys 42:351–360CrossRef

69.

Zehou O, Fabre E, Zelek L, Sbidian E, Ortonne N, Banu E, Wolkenstein P, Valeyrie-Allanore L (2013) Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review. Orphanet J Rare Dis 8:127. https://doi.org/10.1186/1750-1172-8-127CrossRefPubMedPubMedCentral

70.

Puffer RC, Marek T, Stone JJ, Raghunathan A, Howe BM, Spinner RJ (2018) Extensive perineural spread of an intrapelvic sciatic malignant peripheral nerve sheath tumor: a case report. Acta Neurochir 160:1833–1836. https://doi.org/10.1007/s00701-018-3619-4CrossRefPubMed

71.

Martin E, Slooff W-BM, van Houdt WJ, van Dalen T, Verhoef C, Coert JH (2020) Oncological treatment considerations differ across surgical subspecialties treating malignant peripheral nerve sheath tumors: an international survey. Sarcoma 2020:6406439–6406410. https://doi.org/10.1155/2020/6406439CrossRefPubMedPubMedCentral

72.

Clarkson PW, Griffin AM, Catton CN, O'Sullivan B, Ferguson PC, Wunder JS, Bell RS (2005) Epineural dissection is a safe technique that facilitates limb salvage surgery. Clin Orthop Relat Res 438:92–96CrossRef

73.

Gerrand CH, Wunder JS, Kandel RA, O’Sullivan B, Catton CN, Bell RS, Griffin AM, Davis AM (2001) Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence. J Bone Joint Surg (Br) 83:1149–1155CrossRef

74.

Dunn GP, Spiliopoulos K, Plotkin SR, Hornicek FJ, Harmon DC, Delaney TF, Williams Z (2013) Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis Type 1: clinical article. J Neurosurg 118:142–148. https://doi.org/10.3171/2012.9.JNS101610CrossRefPubMed

75.

Mundinger GS, Prucz RB, Frassica FJ, Deune EG (2014) Concomitant upper extremity soft tissue sarcoma limb-sparing resection and functional reconstruction: assessment of outcomes and costs of surgery. Hand (N Y) 9:196–204. https://doi.org/10.1007/s11552-013-9567-9CrossRef

76.

Martin E, Dullaart MJ, van de Sande MAJ, et al (2019) Resuscitating extremities after soft tissue sarcoma resections: are functional reconstructions an overlooked option in limb salvage? A systematic review. Eur J Surg Oncol in press: https://doi.org/10.1016/j.ejso.2019.05.024

77.

Martin E, Dullaart MJ, Verhoef C, Coert JH (2020) A systematic review of functional outcomes after nerve reconstruction in extremity soft tissue sarcomas: a need for general implementation in the armamentarium. J Plast Reconstr Aesthet Surg 73:621–632. https://doi.org/10.1016/j.bjps.2019.12.010CrossRefPubMed

78.

Spiliopoulos K, Williams Z (2011) Brachial plexus reconstruction following resection of a malignant peripheral nerve sheath tumor: case report. Neurosurgery 69:E245–E250. https://doi.org/10.1227/NEU.0b013e31821867deCrossRefPubMed

79.

Costales JR, Socolovsky M, Sanchez Lazaro JA, Alvarez Garcia R (2019) Peripheral nerve injuries in the pediatric population: a review of the literature. Part I: traumatic nerve injuries. Childs Nerv Syst 35:29–35. https://doi.org/10.1007/s00381-018-3974-8CrossRefPubMed

80.

Slump J, Hofer SOP, Ferguson PC, Wunder JS, Griffin AM, Hoekstra HJ, Bastiaannet E, O'Neill AC (2018) Flap reconstruction does not increase complication rates following surgical resection of extremity soft tissue sarcoma. Eur J Surg Oncol 44:251–259. https://doi.org/10.1016/j.ejso.2017.11.015CrossRefPubMed

81.

Barwick WJ, Goldberg JA, Scully SP, Harrelson JM (1992) Vascularized tissue transfer for closure of irradiated wounds after soft tissue sarcoma resection. Ann Surg 216:591–595CrossRef

82.

J. K, A. G, M. T, et al (2014) Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Front Oncol 4: . doi: 10.3389/fonc.2014.00324LK - http://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=2234943X&id=doi:10.3389%2Ffonc.2014.00324&atitle=Radiation+therapy+in+management+of+sporadic+and+neurofibromatosis+type+1-associated+malignant+peripheral+nerve+sheath+tumors&stitle=Front.+Oncol.&title=Frontiers+in+Oncology&volume=4&issue=NOV&spage=&epage=&aulast=Kahn&aufirst=Jenna&auinit=J.&aufull=Kahn+J.&coden=&isbn=&pages=-&date=2014&auinit1=J&auinitm=

83.

Ferrari A, Bisogno G, Carli M (2007) Management of childhood malignant peripheral nerve sheath tumor. Paediatr Drugs 9:239–248CrossRef

84.

Kaushal A, Citrin D (2008) The role of radiation therapy in the management of sarcomas. Surg Clin North Am 88:629–646, viii. https://doi.org/10.1016/j.suc.2008.03.005CrossRefPubMedPubMedCentral

85.

Davis A, O’Sullivan B, Turcotte R et al (2005) Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol 75:48–53. https://doi.org/10.1016/j.radonc.2004.12.020CrossRefPubMed

86.

O’Sullivan B, Davis AM, Turcotte R et al (2002) Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet (London, England) 359:2235–2241. https://doi.org/10.1016/S0140-6736(02)09292-9CrossRef

87.

Clark MA, Fisher C, Judson I, Thomas JM (2005) Soft-tissue sarcomas in adults. N Engl J Med 353:701–711. https://doi.org/10.1056/NEJMra041866CrossRefPubMed

88.

Hawkins DS, Spunt SL, Skapek SX (2013) Children’s Oncology Group’s 2013 blueprint for research: soft tissue sarcomas. Pediatr Blood Cancer 60:1001–1008. https://doi.org/10.1002/pbc.24435CrossRefPubMed

89.

Pratt CB, Pappo AS, Gieser P, Jenkins JJ, Salzberg A, Neff J, Rao B, Green D, Thomas P, Marcus R, Parham D, Maurer H (1999) Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol Off J Am Soc Clin Oncol 17:1219. https://doi.org/10.1200/JCO.1999.17.4.1219CrossRef

90.

Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN (2008) Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. J Surg Oncol 97:340–349. https://doi.org/10.1002/jso.20971CrossRefPubMed

91.

von Mehren M, Randall RL, Benjamin RS, Boles S, Bui MM, Conrad EU III, Ganjoo KN, George S, Gonzalez RJ, Heslin MJ, Kane JM III, Koon H, Mayerson J, McCarter M, McGarry SV, Meyer C, O'Donnell RJ, Pappo AS, Paz IB, Petersen IA, Pfeifer JD, Riedel RF, Schuetze S, Schupak KD, Schwartz HS, Tap WD, Wayne JD, Bergman MA, Scavone J (2016) Soft tissue sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 14:758–786CrossRef

92.

Higham CS, Steinberg SM, Dombi E, Perry A, Helman LJ, Schuetze SM, Ludwig JA, Staddon A, Milhem MM, Rushing D, Jones RL, Livingston M, Goldman S, Moertel C, Wagner L, Janhofer D, Annunziata CM, Reinke D, Long L, Viskochil D, Baker L, Widemann BC (2017) SARC006: phase II trial of chemotherapy in sporadic and neurofibromatosis type 1 associated chemotherapy-naive malignant peripheral nerve sheath tumors. Sarcoma 2017:8685638–8685638. https://doi.org/10.1155/2017/8685638CrossRefPubMedPubMedCentral

93.

Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim AR, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC (2016) Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med 375:2550–2560. https://doi.org/10.1056/NEJMoa1605943CrossRefPubMedPubMedCentral

94.

Tap WD, Jones RL, Van Tine BA et al (2016) Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet (London, England) 388:488–497. https://doi.org/10.1016/S0140-6736(16)30587-6CrossRef

95.

Robertson KA, Nalepa G, Yang F-C, Bowers DC, Ho CY, Hutchins GD, Croop JM, Vik TA, Denne SC, Parada LF, Hingtgen CM, Walsh LE, Yu M, Pradhan KR, Edwards-Brown MK, Cohen MD, Fletcher JW, Travers JB, Staser KW, Lee MW, Sherman MR, Davis CJ, Miller LC, Ingram DA, Clapp DW (2012) Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Lancet Oncol 13:1218–1224. https://doi.org/10.1016/S1470-2045(12)70414-XCrossRefPubMedPubMedCentral

96.

Chugh R, Wathen JK, Maki RG, Benjamin RS, Patel SR, Myers PA, Priebat DA, Reinke DK, Thomas DG, Keohan ML, Samuels BL, Baker LH (2009) Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol 27:3148–3153. https://doi.org/10.1200/JCO.2008.20.5054CrossRefPubMed

97.

Ferguson MJ, Rhodes SD, Jiang L, Li X, Yuan J, Yang X, Zhang S, Vakili ST, Territo P, Hutchins G, Yang FC, Ingram DA, Clapp DW, Chen S (2016) Preclinical evidence for the use of sunitinib malate in the treatment of plexiform neurofibromas. Pediatr Blood Cancer 63:206–213. https://doi.org/10.1002/pbc.25763CrossRefPubMed

98.

Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, Balis FM, Jayaprakash N, Turkbey B, Muradyan N, Choyke PL, Reddy A, Korf B, Widemann BC (2013) Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr Blood Cancer 60:396–401. https://doi.org/10.1002/pbc.24281CrossRefPubMed

99.

Ahsan S, Ge Y, Tainsky MA (2016) Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1-associated malignant peripheral nerve sheath tumors. Oncotarget 7:57171–57185. https://doi.org/10.18632/oncotarget.11036CrossRefPubMedPubMedCentral

100.

Albritton KH, Rankin C, Coffin CM, Ratner N, Budd GT, Schuetze SM, Randall RL, Declue JE, Borden EC (2006) Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST). J Clin Oncol 24:9518. https://doi.org/10.1200/jco.2006.24.18_suppl.9518CrossRef

101.

Maki RG, D’Adamo DR, Keohan ML et al (2009) Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 27:3133–3140. https://doi.org/10.1200/JCO.2008.20.4495CrossRefPubMedPubMedCentral

102.

Schuetze SM, Wathen JK, Lucas DR, Choy E, Samuels BL, Staddon AP, Ganjoo KN, von Mehren M, Chow WA, Loeb DM, Tawbi HA, Rushing DA, Patel SR, Thomas DG, Chugh R, Reinke DK, Baker LH (2016) SARC009: phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer 122:868–874. https://doi.org/10.1002/cncr.29858CrossRefPubMed

103.

Martin E, Lamba N, Flucke UE, Verhoef C, Coert JH, Versleijen-Jonkers YMH, Desar IME (2019) Non-cytotoxic systemic treatment in malignant peripheral nerve sheath tumors (MPNST): a systematic review from bench to bedside. Crit Rev Oncol Hematol 138:223–232. https://doi.org/10.1016/j.critrevonc.2019.04.007CrossRefPubMed

104.

Widemann BC, Meyer CF, Cote GM, Chugh R, Milhem MM, van Tine BA, Kim AR, Turpin B, Dombi E, Jayaprakash N, Okuno SH, Helman LJ, Onwudiwe N, Steinberg SM, Reinke DK, Cichowski K, Perentesis JP (2016) 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 34:11053. https://doi.org/10.1200/JCO.2016.34.15_suppl.11053CrossRef

105.

Tsuchida T, Otsuka H, Niimura M, Inoue Y, Kukita A, Hashimoto Y, Seyama Y, Yamakawa T (1984) Biochemical study on gangliosides in neurofibromas and neurofibrosarcomas of Recklinghausen’s disease. J Dermatol 11:129–138. https://doi.org/10.1111/j.1346-8138.1984.tb01454.xCrossRefPubMed

106.

Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM, Children's Oncology Group (2010) Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 363:1324–1334. https://doi.org/10.1056/NEJMoa0911123CrossRefPubMedPubMedCentral

107.

D’Angelo SP, Mahoney MR, Van Tine BA et al (2018) Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol 19:416–426. https://doi.org/10.1016/S1470-2045(18)30006-8CrossRefPubMedPubMedCentral

Title: Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease
Authors: Enrico Martin
Uta E. Flucke
J. Henk Coert
Max M. van Noesel
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Keywords: Radiotherapy
Neurofibromatosis Type 1
Cytostatic Therapy
Published in: Child's Nervous System / Issue 10/2020
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-020-04687-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 10/2020

James Tait Goodrich: a collector of friends

Genetics of tuberous sclerosis complex: an update

Epilepsy surgery in tuberous sclerosis complex (TSC): emerging techniques and redefinition of treatment goals

In memory of James Tait Goodrich

New treatment modalities in NF-related neuroglial tumors

Craniofacial bone alterations in patients with neurofibromatosis type 1