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Primary CNS Lymphoma

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Book cover Radiation Therapy in Hematologic Malignancies

Abstract

Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal form of non-Hodgkin lymphoma affecting the brain, leptomeninges, eyes, or the spinal cord, in the absence of systemic involvement. The predominant risk factor for disease development is immunodeficiency. PCNSL is an acquired immune deficiency syndrome (AIDS) defining malignancy; however, the incidence in this patient population is decreasing due to advancements in antiretroviral treatment. On the other hand, among immunocompetent individuals, the incidence of PCNSL has increased over the past few decades, representing 3–4 % of all primary brain tumors (Eby et al. Cancer 62(11):2461–2465, 1988). The explanation for the growing incidence is not clear. PCNSL has a predilection for the elderly population with a median age of diagnosis of 55 years and peak incidence in the sixth and seventh decades of life (Hochberg and Miller, J Neurosurg 68(6):835–853, 1988; Fine and Mayer, Ann Intern Med 119(11):1093–1104, 1993).

The cornerstone of therapy is a systemic treatment with intravenous high-dose methotrexate (Mtx). There is an ongoing controversy regarding the role of consolidative therapies, including radiation therapy (RT) and autologous stem cell transplantation (ASCT). In this review, we will explore diagnostic considerations, prognosis, as well as primary and salvage therapy for PCNSL. We will highlight the data supporting various therapeutic strategies, with an emphasis on the role of RT in this rare hematologic malignancy.

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References

  1. Eby NL, et al. Increasing incidence of primary brain lymphoma in the US. Cancer. 1988;62(11):2461–5.

    Article  CAS  PubMed  Google Scholar 

  2. Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg. 1988;68(6):835–53.

    Article  CAS  PubMed  Google Scholar 

  3. Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med. 1993;119(11):1093–104.

    Article  CAS  PubMed  Google Scholar 

  4. Bataille B, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg. 2000;92(2):261–6.

    Article  CAS  PubMed  Google Scholar 

  5. Peterson K, et al. The clinical spectrum of ocular lymphoma. Cancer. 1993;72(3):843–9.

    Article  CAS  PubMed  Google Scholar 

  6. Ursea R, et al. Ophthalmic, ultrasonographic findings in primary central nervous system lymphoma with ocular involvement. Retina. 1997;17(2):118–23.

    Article  CAS  PubMed  Google Scholar 

  7. Grimm SA, et al. Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Ann Oncol. 2007;18(11):1851–5.

    Article  CAS  PubMed  Google Scholar 

  8. Char DH, et al. Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology. 1988;95(5):625–30.

    Article  CAS  PubMed  Google Scholar 

  9. Shenkier TN, et al. Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group. J Clin Oncol. 2005;23(10):2233–9.

    Article  PubMed  Google Scholar 

  10. Monabati A, et al. Primary burkitt lymphoma of the brain in an immunocompetent patient. Case report. J Neurosurg. 2002;96(6):1127–9.

    Article  PubMed  Google Scholar 

  11. Tu PH, et al. Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma. J Clin Oncol. 2005;23(24):5718–27.

    Article  PubMed  Google Scholar 

  12. Kluin PM, Deckert M, Ferry JA. Primary diffuse large B cell lymphoma of the CNS., in WHO classification of tumours of haematopoietic and lymphoid tissue (IARC WHO Classification of tumours). Lyon: IARC; 2008. p. 240–1.

    Google Scholar 

  13. Giannini C, Dogan A, Salomao DR. CNS lymphoma: a practical diagnostic approach. J Neuropathol Exp Neurol. 2014;73(6):478–94.

    Article  CAS  PubMed  Google Scholar 

  14. Alizadeh AA, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.

    Article  CAS  PubMed  Google Scholar 

  15. Bea S, et al. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood. 2005;106(9):3183–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hans CP, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.

    Article  CAS  PubMed  Google Scholar 

  17. Brunn A, et al. Frequent triple-hit expression of MYC, BCL2, and BCL6 in primary lymphoma of the central nervous system and absence of a favorable MYC(low)BCL2 (low) subgroup may underlie the inferior prognosis as compared to systemic diffuse large B-cell lymphomas. Acta Neuropathol. 2013;126(4):603–5.

    Article  PubMed  Google Scholar 

  18. Gill KZ, et al. MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system. PLoS One. 2014;9(12):e114398.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Klapper W, et al. Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Leukemia. 2008;22(12):2226–9.

    Article  CAS  PubMed  Google Scholar 

  20. Akyurek N, et al. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 2012;118(17):4173–83.

    Article  CAS  PubMed  Google Scholar 

  21. Cady FM, et al. Del(6)(q22) and BCL6 rearrangements in primary CNS lymphoma are indicators of an aggressive clinical course. J Clin Oncol. 2008;26(29):4814–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mansour A, et al. MR imaging features of intracranial primary CNS lymphoma in immune competent patients. Cancer Imaging. 2014;14(1):22.

    PubMed  PubMed Central  Google Scholar 

  23. Porter AB, et al. Primary central nervous system lymphoma can be histologically diagnosed after previous corticosteroid use: a pilot study to determine whether corticosteroids prevent the diagnosis of primary central nervous system lymphoma. Ann Neurol. 2008;63(5):662–7.

    Article  CAS  PubMed  Google Scholar 

  24. DeAngelis LM, et al. Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy. Neurology. 1990;40(1):80–6.

    Article  CAS  PubMed  Google Scholar 

  25. Weller M, et al. Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol. 2012;14(12):1481–4.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nelson DF, et al. Non-Hodgkin’s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys. 1992;23(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  27. Schultz C, et al. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88–06. J Clin Oncol. 1996;14(2):556–64.

    CAS  PubMed  Google Scholar 

  28. Borsi JD, Moe PJ. A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5 g to 33.6 g/m2 in children with acute lymphoblastic leukemia. Cancer. 1987;60(1):5–13.

    Article  CAS  PubMed  Google Scholar 

  29. Shapiro WR, Young DF, Mehta BM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293(4):161–6.

    Article  CAS  PubMed  Google Scholar 

  30. DeAngelis LM, et al. Combined modality therapy for primary CNS lymphoma. J Clin Oncol. 1992;10(4):635–43.

    CAS  PubMed  Google Scholar 

  31. Ferreri AJ, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009;374(9700):1512–20.

    Article  CAS  PubMed  Google Scholar 

  32. Glass J, et al. Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg. 1994;81(2):188–95.

    Article  CAS  PubMed  Google Scholar 

  33. O’Brien PC, et al. Combined-modality therapy for primary central nervous system lymphoma: long-term data from a Phase II multicenter study (Trans-Tasman Radiation Oncology Group). Int J Radiat Oncol Biol Phys. 2006;64(2):408–13.

    Article  PubMed  Google Scholar 

  34. Abrey LE, DeAngelis LM, Yahalom J. Long-term survival in primary CNS lymphoma. J Clin Oncol. 1998;16(3):859–63.

    CAS  PubMed  Google Scholar 

  35. Citterio G, Ferreri AJ, Reni M. Current uses of radiation therapy in patients with primary CNS lymphoma. Expert Rev Anticancer Ther. 2013;13(11):1327–37.

    Article  CAS  PubMed  Google Scholar 

  36. Abrey LE, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol. 2005;23(22):5034–43.

    Article  PubMed  Google Scholar 

  37. Kasenda B, et al. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012;23(10):2670–5.

    Article  CAS  PubMed  Google Scholar 

  38. Omuro A, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015;125:1403–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rubenstein JL, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013;31(25):3061–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hottinger AF, et al. Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology. 2007;69(11):1178–82.

    Article  PubMed  Google Scholar 

  41. Nguyen PL, et al. Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol. 2005;23(7):1507–13.

    Article  PubMed  Google Scholar 

  42. Shibamoto Y, et al. Is whole-brain irradiation necessary for primary central nervous system lymphoma? Patterns of recurrence after partial-brain irradiation. Cancer. 2003;97(1):128–33.

    Article  PubMed  Google Scholar 

  43. Matsumoto Y, et al. Effectiveness and limitation of gamma knife radiosurgery for relapsed central nervous system lymphoma: a retrospective analysis in one institution. Int J Hematol. 2007;85(4):333–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit #97, Houston, TX, 77030, USA

    Chelsea Pinnix MD, PhD

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  1. Chelsea Pinnix MD, PhD
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Correspondence to Chelsea Pinnix MD, PhD .

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Editors and Affiliations

  1. University of Texas, MD Anderson Cancer Center, Houston, Texas, USA

    Bouthaina Shbib Dabaja

  2. Dana-Farber Cancer Institute, Harvard University Medical School, Boston, Massachusetts, USA

    Andrea K. Ng

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© 2017 Springer International Publishing Switzerland

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Pinnix, C. (2017). Primary CNS Lymphoma. In: Dabaja, B., Ng, A. (eds) Radiation Therapy in Hematologic Malignancies . Springer, Cham. https://doi.org/10.1007/978-3-319-42615-0_8

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  • DOI: https://doi.org/10.1007/978-3-319-42615-0_8

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-42613-6

  • Online ISBN: 978-3-319-42615-0

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