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Primary and secondary gliosarcomas: clinical, molecular and survival characteristics

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Abstract

Gliosarcoma is classified by the World Health Organization as a variant of glioblastoma. These tumors exhibit biphasic histologic and immunophenotypic features, reflecting both glial and mesenchymal differentiation. Gliosarcomas can be further classified into primary (de novo) tumors, and secondary gliosarcomas, which are diagnosed at recurrence after a diagnosis of glioblastoma. Using a retrospective review, patients seen at MD Anderson Cancer Center between 2004 and 2014 with a pathology-confirmed diagnosis of gliosarcoma were identified. 34 patients with a diagnosis of gliosarcoma seen at the time of initial diagnosis or at recurrence were identified (24 primary gliosarcomas (PGS), 10 secondary gliosarcomas (SGS)). Molecular analysis performed on fourteen patients revealed a high incidence of TP53 mutations and, rarely, EGFR and IDH mutations. Median overall survival (OS) for all patients was 17.5 months from the diagnosis of gliosarcoma, with a progression free survival (PFS) of 6.4 months. Comparing PGS with SGS, the median OS was 24.7 and 8.95 months, respectively (from the time of sarcomatous transformation in the case of SGS). The median OS in SGS patients from the initial diagnosis of GB was 25 months, with a PFS of 10.7 months. Molecular analysis revealed a higher than expected rate of TP53 mutations in GS patients and, typical of primary glioblastoma, IDH mutations were uncommon. Though our data shows improved outcomes for both PGS and SGS when compared to the literature, this is most likely a reflection of selection bias of patients treated on clinical trials at a quaternary center.

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References

  1. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):iv1–iv63. doi:10.1093/neuonc/nou223

    Article  PubMed Central  PubMed  Google Scholar 

  2. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773. doi:10.1056/NEJMoa0808710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602. doi:10.1007/s00401-008-0455-2

    Article  CAS  PubMed  Google Scholar 

  4. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153. doi:10.2353/ajpath.2009.080958

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. doi:10.1007/s00401-007-0243-4

    Article  PubMed Central  PubMed  Google Scholar 

  6. Karsy M, Gelbman M, Shah P, Balumbu O, Moy F, Arslan E (2012) Established and emerging variants of glioblastoma multiforme: review of morphological and molecular features. Folia Neuropathol 50:301–321

    Article  PubMed  Google Scholar 

  7. Beaumont TL, Kupsky WJ, Barger GR, Sloan AE (2007) Gliosarcoma with multiple extracranial metastases: case report and review of the literature. J Neurooncol 83:39–46. doi:10.1007/s11060-006-9295-x

    Article  PubMed  Google Scholar 

  8. Han SJ, Yang I, Ahn BJ, Otero JJ, Tihan T, McDermott MW, Berger MS, Prados MD, Parsa AT (2010) Clinical characteristics and outcomes for a modern series of primary gliosarcoma patients. Cancer 116:1358–1366. doi:10.1002/cncr.24857

    Article  PubMed  Google Scholar 

  9. Han SJ, Yang I, Tihan T, Prados MD, Parsa AT (2010) Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity. J Neurooncol 96:313–320. doi:10.1007/s11060-009-9973-6

    Article  PubMed Central  PubMed  Google Scholar 

  10. Galanis E, Buckner JC, Dinapoli RP, Scheithauer BW, Jenkins RB, Wang CH, O’Fallon JR, Farr G Jr (1998) Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results. J Neurosurg 89:425–430. doi:10.3171/jns.1998.89.3.0425

    Article  CAS  PubMed  Google Scholar 

  11. Perry JR, Ang LC, Bilbao JM, Muller PJ (1995) Clinicopathologic features of primary and postirradiation cerebral gliosarcoma. Cancer 75:2910–2918

    Article  CAS  PubMed  Google Scholar 

  12. Han SJ, Yang I, Otero JJ, Ahn BJ, Tihan T, McDermott MW, Berger MS, Chang SM, Parsa AT (2010) Secondary gliosarcoma after diagnosis of glioblastoma: clinical experience with 30 consecutive patients. J Neurosurg 112:990–996. doi:10.3171/2009.9.jns09931

    Article  PubMed  Google Scholar 

  13. Han SJ, Yang I, Tihan T, Chang SM, Parsa AT (2010) Secondary gliosarcoma: a review of clinical features and pathological diagnosis. J Neurosurg 112:26–32. doi:10.3171/2009.3.jns081081

    Article  PubMed  Google Scholar 

  14. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  15. Stroebe H Über Entstehung und Bau der Hirngliome. Zieglers Beiträge. 1895. Bd XVIII 3

  16. Feigin I, Allen LB, Lipkin L, Gross SW (1958) The endothelial hyperplasia of the cerebral blood vessels with brain tumors, and its sarcomatous transformation. Cancer 11:264–277

    Article  CAS  PubMed  Google Scholar 

  17. Paulus W, Bayas A, Ott G, Roggendorf W (1994) Interphase cytogenetics of glioblastoma and gliosarcoma. Acta Neuropathol 88:420–425

    Article  CAS  PubMed  Google Scholar 

  18. Agale SV, Bhatia VO, D’Costa GF, Velho V, Domkundwar S, Mandal S Gliosarcoma Arising in Anaplastic Ependymoma with Heterologous Sarcomatous Component: A Rare Phenomenon. Spine Neurosurg

  19. Rodriguez FJ, Scheithauer BW, Perry A, Oliveira AM, Jenkins RB, Oviedo A, Mork SJ, Palmer CA, Burger PC (2008) Ependymal tumors with sarcomatous change (“ependymosarcoma”): a clinicopathologic and molecular cytogenetic study. Am J Surg Pathol 32:699–709. doi:10.1097/PAS.0b013e318158234e

    Article  PubMed  Google Scholar 

  20. Kepes JJ, Bastian FO, Weber ED (1996) Gliosarcoma developing from an irradiated ependymoma. Acta Neuropathol 92:515–519

    Article  CAS  PubMed  Google Scholar 

  21. Banerjee AK, Sharma BS, Kak VK, Ghatak NR (1989) Gliosarcoma with cartilage formation. Cancer 63:518–523

    Article  CAS  PubMed  Google Scholar 

  22. Barresi V, Cerasoli S, Morigi F, Cremonini AM, Volpini M, Tuccari G (2006) Gliosarcoma with features of osteoblastic osteosarcoma: a review. Arch Pathol Lab Med 130:1208–1211

    PubMed  Google Scholar 

  23. Barut F, Kandemir NO, Ozdamar SO, Gul S, Bektas S, Gun BD, Bahadir B (2009) Gliosarcoma with chondroblastic osteosarcomatous differentation: report of two case with clinicopathologic and immunohistochemical features. Turk Neurosurg 19:417–422

    PubMed  Google Scholar 

  24. Hayashi K, Ohara N, Jeon HJ, Akagi S, Takahashi K, Akagi T, Namba S (1993) Gliosarcoma with features of chondroblastic osteosarcoma. Cancer 72:850–855

    Article  CAS  PubMed  Google Scholar 

  25. Barnard RO, Bradford R, Scott T, Thomas DG (1986) Gliomyosarcoma. Report of a case of rhabdomyosarcoma arising in a malignant glioma. Acta Neuropathol 69:23–27

    Article  CAS  PubMed  Google Scholar 

  26. Haddad SF, Moore SA, Schelper RL, Goeken JA (1992) Smooth muscle can comprise the sarcomatous component of gliosarcomas. J Neuropathol Exp Neurol 51:493–498

    Article  CAS  PubMed  Google Scholar 

  27. Biernat W, Aguzzi A, Sure U, Grant JW, Kleihues P, Hegi ME (1995) Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells. J Neuropathol Exp Neurol 54:651–656

    Article  CAS  PubMed  Google Scholar 

  28. Meis JM, Martz KL, Nelson JS (1991) Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases. Cancer 67:2342–2349

    Article  CAS  PubMed  Google Scholar 

  29. Actor B, Cobbers JM, Buschges R, Wolter M, Knobbe CB, Lichter P, Reifenberger G, Weber RG (2002) Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer 34:416–427. doi:10.1002/gcc.10087

    Article  CAS  PubMed  Google Scholar 

  30. Boerman RH, Anderl K, Herath J, Borell T, Johnson N, Schaeffer-Klein J, Kirchhof A, Raap AK, Scheithauer BW, Jenkins RB (1996) The glial and mesenchymal elements of gliosarcomas share similar genetic alterations. J Neuropathol Exp Neurol 55:973–981

    Article  CAS  PubMed  Google Scholar 

  31. Reis RM, Konu-Lebleblicioglu D, Lopes JM, Kleihues P, Ohgaki H (2000) Genetic profile of gliosarcomas. Am J Pathol 156:425–432. doi:10.1016/s0002-9440(10)64746-3

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Mueller W, Lass U, Herms J, Kuchelmeister K, Bergmann M, von Deimling A (2001) Clonal analysis in glioblastoma with epithelial differentiation. Brain Pathol 11:39–43

    Article  CAS  PubMed  Google Scholar 

  33. Lee D, Kang SY, Suh YL, Jeong JY, Lee JI, Nam DH (2012) Clinicopathologic and genomic features of gliosarcomas. J Neurooncol 107:643–650. doi:10.1007/s11060-011-0790-3

    Article  PubMed  Google Scholar 

  34. Reis RM, Martins A, Ribeiro SA, Basto D, Longatto-Filho A, Schmitt FC, Lopes JM (2005) Molecular characterization of PDGFR-alpha/PDGF-A and c-KIT/SCF in gliosarcomas. Cell Oncol 27:319–326

    CAS  PubMed  Google Scholar 

  35. Simmons ML, Lamborn KR, Takahashi M, Chen P, Israel MA, Berger MS, Godfrey T, Nigro J, Prados M, Chang S, Barker FG 2nd, Aldape K (2001) Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res 61:1122–1128

    CAS  PubMed  Google Scholar 

  36. Ohgaki H, Kleihues P (2013) The definition of primary and secondary glioblastoma. Clin Cancer Res 19:764–772. doi:10.1158/1078-0432.ccr-12-3002

    Article  CAS  PubMed  Google Scholar 

  37. Gjerdrum LM, Bojsen-Moller M (1999) October 1998—61 year old male with brain tumor and oral, lung, and palpebral masses. Brain Pathol 9:421–422

    CAS  PubMed  Google Scholar 

  38. Ojeda VJ, Sterrett GF (1984) Cerebral gliosarcoma, pulmonary adenoid-cystic carcinoma, and pulmonary metastatic gliosarcoma: report of an untreated case. Pathology 16:217–221

    Article  CAS  PubMed  Google Scholar 

  39. Weaver D, Vandenberg S, Park TS, Jane JA (1984) Selective peripancreatic sarcoma metastases from primary gliosarcoma. Case report. J Neurosurg 61:599–601. doi:10.3171/jns.1984.61.3.0599

    CAS  PubMed  Google Scholar 

  40. Robert M, Wastie M (2008) Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases. Biomed Imaging Interv J 4:e3. doi:10.2349/biij.4.1.e3

    Article  PubMed Central  PubMed  Google Scholar 

  41. Beauchesne P (2011) Extra-neural metastases of malignant gliomas: myth or reality? Cancers (Basel) 3:461–477. doi:10.3390/cancers3010461

    Article  Google Scholar 

  42. Mandel JJ, Yust-Katz S, Cachia D, Wu J, Liu D, de Groot JF, Yung AW, Gilbert MR (2014) Leptomeningeal dissemination in glioblastoma; an inspection of risk factors, treatment, and outcomes at a single institution. J Neurooncol 120:597–605. doi:10.1007/s11060-014-1592-1

    Article  CAS  PubMed  Google Scholar 

  43. Mansouri B, Barboriak DP, Kilani RK (2013) Gliosarcoma metastatic to the leptomeninges and dura. J Neuroimaging 23:245–247. doi:10.1111/j.1552-6569.2011.00641.x

    Article  PubMed  Google Scholar 

  44. Singh G, Mallick S, Sharma V, Joshi N, Purkait S, Jha P, Sharma MC, Suri V, Julka PK, Mahapatra AK, Singh M, Kale SS, Sarkar C (2012) A study of clinico-pathological parameters and O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status in the prognostication of gliosarcoma. Neuropathology 32:534–542. doi:10.1111/j.1440-1789.2012.01297.x

    Article  PubMed  Google Scholar 

  45. Morantz RA, Feigin I, Ransohoff J 3rd (1976) Clinical and pathological study of 24 cases of gliosarcoma. J Neurosurg 45:398–408. doi:10.3171/jns.1976.45.4.0398

    Article  CAS  PubMed  Google Scholar 

  46. Parekh HC, O’Donovan DG, Sharma RR, Keogh AJ (1995) Primary cerebral gliosarcoma: report of 17 cases. Br J Neurosurg 9:171–178

    Article  CAS  PubMed  Google Scholar 

  47. Lutterbach J, Guttenberger R, Pagenstecher A (2001) Gliosarcoma: a clinical study. Radiother Oncol 61:57–64

    Article  CAS  PubMed  Google Scholar 

  48. Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, Fisher J (2010) Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res 16:2443–2449. doi:10.1158/1078-0432.ccr-09-3106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15:943–953. doi:10.1016/s1470-2045(14)70314-6

    Article  CAS  PubMed  Google Scholar 

  50. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi:10.1056/NEJMoa1308345

    Article  CAS  PubMed  Google Scholar 

  51. Phillips H, Sandmann T, Li C, Cloughesy T, Chinot OL, Wick W, Nishikawa R, Mason W, Henriksson R, Saran F, Lai A, Moore N, Hegde P, Abrey L, Bourgon R, Garcia J, Bais C (2014) BI-22correlation of molecular subtypes with overall survival (OS) in avaglio, a randomized, placebo-controlled study of bevacizumab (BEV) plus radiotherapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GBM). Neuro Oncol 16:v28. doi:10.1093/neuonc/nou239.22

    Article  Google Scholar 

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Acknowledgments

We thank Dr Funda Meric-Bernstam MD and Dr Kenna R Shaw PhD for their invaluable support in preparation of this manuscript. This work was supported in part by the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, and the MD Anderson Cancer Center Support grant (P30 CA016672). A Olar was supported by the National Institutes of Health/National Cancer Institute (Training Grant No. 5T32CA163185). T.S. Armstrong serves as consultant for Immunocellular therapeutics;is on the advisory board for Roche; receives research support from Merck and Genentech. M.R. Gilbert reports research support from Genentech, Merck, Glaxo Smith Kline; receives honoraria from Merck, Genentech, AbbVie; and serves on the advisory board for Genetech, AbbVie, Heron Therapeutics. JF de Groot serves as a consultant for Celldex and Deciphera Pharmaceuticals; serves on the advisory board for Genentech, Novartis, Celldex, is on the Data and Safety Monitoring Board for VBL Therapeutics and receives research support from Sanofi-Aventis, AstraZeneca, EMD-Serono, Eli Lilly, Novartis, Deciphera Pharmaceuticals.

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    Authors and Affiliations

    1. Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St, Charleston, SC, 29425, USA

      David Cachia

    2. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

      Carlos Kamiya-Matsuoka, Terri S. Armstrong & John F. De Groot

    3. Department of Neurology, Baylor College of Medicine, 6550 Fannin St, Houston, TX, 77030, USA

      Jacob J. Mandel

    4. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

      Adriana Olar & Gregory N. Fuller

    5. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6565 Fannin Street, Houston, TX, 77030, USA

      Matthew D. Cykowski

    6. Department of Family Health, The University of Texas Health Science Center School of Nursing, 6901 Bertner Ave, Houston, TX, USA

      Terri S. Armstrong

    7. Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 82, Bethesda, MD, 20892, USA

      Mark R. Gilbert

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    David Cachia and Carlos Kamiya-Matsuoka have contributed equally to this work.

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    Cachia, D., Kamiya-Matsuoka, C., Mandel, J.J. et al. Primary and secondary gliosarcomas: clinical, molecular and survival characteristics. J Neurooncol 125, 401–410 (2015). https://doi.org/10.1007/s11060-015-1930-y

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