Skip to main content

Advertisement

Log in

Impact of therapeutic regimen and clinical presentation on overall survival in CNS lymphoma

  • Experimental research - Brain Tumors
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

The authors present a retrospective analysis of 45 patients who underwent treatment of CNS lymphoma (both primary and secondary) at a single institution between 2005 and 2012.

Methods

This study involves 21 female and 24 male patients with a mean age of 59.2 years. All medical records and pathology reports were reviewed for each patient. Univariate and multivariate analyses of overall survival were performed.

Results

Presentation with altered mental status was a significant risk factor for worse overall survival. An HIV infection, deep lesion location, and age over 60 did not impact survival. A survival benefit was demonstrated with the use of systemic therapy, specifically rituximab, and radiation. The CNS Lymphoma Score was derived from this cohort, which proved a powerful predictive tool for overall survival. The surgical complication rate in this series was 17.8 %.

Conclusions

This study highlights the prognostic importance of presenting mental status on outcomes in CNS lymphoma and demonstrates a summative benefit of rituximab and whole brain radiation therapy. Considering these factors together provides an easily applicable and meaningful stratification for this patient population. The surgical complication rate in this patient population is not negligible. The high percentage of wound-related surgical complications suggests the need for a waiting period between surgery and initiation of chemotherapy to allow for wound healing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ferreri AJM, Abrey LE, Blay J-Y, Borisch B, Hochman J, Neuwelt E, Yahalom J, Zucca E, Cavalli F, Armitage J, Batchelor T (2003) Summary statement on primary central nervous system lymphomas from the Eighth international conference on malignant lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol 21(12):2407–2414

    Article  PubMed  Google Scholar 

  2. DeAngelis LM (2009) Primary central nervous system lymphoma: Coming or going? Blood 113(19):4483–4484

    Article  CAS  PubMed  Google Scholar 

  3. Baraniskin A, Deckert M, Schulte-Altedorneburg G, Schlegel U, Schroers R (2012) Current strategies in the diagnosis of diffuse large B-cell lymphoma of the central nervous system. Br J Haematol 156(4):421–432

    Article  PubMed  Google Scholar 

  4. Prica A, Chan K, Cheung MC (2012) Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: A decision analysis. Br J Haematol 158(5):600–607

    Article  CAS  PubMed  Google Scholar 

  5. Olson JE, Janney CA, Rao RD, Cerhan JR, Kurtin PJ, Schiff D, Kaplan RS, O’Neill BP (2002) The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: A surveillance, epidemiology, and end results analysis. Cancer 95(7):1504–1510

    Article  PubMed  Google Scholar 

  6. Abrey LE, Yahalom J, DeAngelis LM (2000) Treatment for primary CNS lymphoma: The next step. J Clin Oncol 18(17):3144–3150

    CAS  PubMed  Google Scholar 

  7. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ (2002) Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation therapy oncology group study 93–10. J Clin Oncol 20(24):4643–4648

    Article  PubMed  Google Scholar 

  8. Poortmans PMP, Kluin-Nelemans HC, Haaxma-Reiche H, Van’t Veer M, Hansen M, Soubeyran P, Taphoorn M, Thomas J, Van den Bent M, Fickers M, Van Imhoff G, Rozewicz C, Teodorovic I, van Glabbeke M (2003) High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. J Clin Oncol 21(24):4483–4488

    Article  CAS  PubMed  Google Scholar 

  9. Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE (2006) Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 24(28):4570–4574

    Article  CAS  PubMed  Google Scholar 

  10. Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE (2007) Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 25(30):4730–4735

    Article  CAS  PubMed  Google Scholar 

  11. Villa D, Connors JM, Shenkier TN, Gascoyne RD, Sehn LH, Savage KJ (2010) Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: The impact of the addition of rituximab to CHOP chemotherapy. Ann Oncol 21(5):1046–1052

    Article  CAS  PubMed  Google Scholar 

  12. Bierman P, Giglio P (2005) Diagnosis and treatment of central nervous system involvement in non-Hodgkin’s lymphoma. Hematol Oncol Clin North Am 19(4):597–609, v

    Article  PubMed  Google Scholar 

  13. Doolittle ND, Abrey LE, Shenkier TN, Tali S, Bromberg JE, Neuwelt EA, Soussain C, Jahnke K, Johnston P, Illerhaus G, Schiff D, Batchelor T, Montoto S, Kraemer DF, Zucca E (2008) Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: An international primary CNS lymphoma collaborative group report. Blood 111(3):1085–1093

    Article  CAS  PubMed  Google Scholar 

  14. Akkas BE, Vural GU (2013) The incidence of secondary central nervous system involvement in patients with non-Hodgkin’s lymphoma as detected by 18F-FDG PET/CT. Nucl Med Commun 34(1):50–56

    Article  PubMed  Google Scholar 

  15. Van Besien K, Gisselbrecht C, Pfreundschuh M, Zucca E (2008) Secondary lymphomas of the central nervous system: Risk, prophylaxis and treatment. Leuk Lymphoma 49(Suppl 1):52–58

    Article  PubMed  Google Scholar 

  16. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC (1994) A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 84(5):1361–1392

    CAS  PubMed  Google Scholar 

  17. Chamberlain MC (2006) Lymphomatous meningitis in primary central nervous system lymphoma. Neurosurg Focus 21(5):E6

    Article  PubMed  Google Scholar 

  18. Batchelor T (2006) Primary CNS lymphoma. J Clin Oncol 24(8):1281–1288

    Article  CAS  PubMed  Google Scholar 

  19. Eichler AF, Batchelor TT (2006) Primary central nervous system lymphoma: presentation, diagnosis and staging. Neurosurg Focus 21(5):E15

    Article  PubMed  Google Scholar 

  20. Goldstein JD, Dickson DW, Moser FG, Hirschfeld AD, Freeman K, Llena JF, Kaplan B, Davis L (1991) Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation. Cancer 67(11):2756–2765

    Article  CAS  PubMed  Google Scholar 

  21. Wolf T, Brodt H-R, Fichtlscherer S, Mantzsch K, Hoelzer D, Helm EB, Mitrou PS, Chow KU (2005) Changing incidence and prognostic factors of survival in AIDS-related non-Hodgkin’s lymphoma in the era of highly active antiretroviral therapy (HAART). Leuk Lymphoma 46(2):207–215

    Article  PubMed  Google Scholar 

  22. Jagadeesh D, Woda BA, Draper J, Evens AM (2012) Post transplant lymphoproliferative disorders: Risk, classification, and therapeutic recommendations. Curr Treat Options in Oncol 13(1):122–136

    Article  Google Scholar 

  23. Buell JF, Gross TG, Hanaway MJ, Trofe J, Roy-Chaudhury P, First MR, Woodle ES (2005) Posttransplant lymphoproliferative disorder: Significance of central nervous system involvement. Transplant Proc 37(2):954–955

    Article  CAS  PubMed  Google Scholar 

  24. Miller DC, Hochberg FH, Harris NL, Gruber ML, Louis DN, Cohen H (1994) Pathology with clinical correlations of primary central nervous system non-Hodgkin’s lymphoma. The Massachusetts general hospital experience 1958–1989. Cancer 74(4):1383–1397

    Article  CAS  PubMed  Google Scholar 

  25. Bataille B, Delwail V, Menet E, Vandermarcq P, Ingrand P, Wager M, Guy G, Lapierre F (2000) Primary intracerebral malignant lymphoma: Report of 248 cases. J Neurosurg 92(2):261–266

    Article  CAS  PubMed  Google Scholar 

  26. Schwechheimer K, Braus DF, Schwarzkopf G, Feller AC, Volk B, Müller-Hermelink HK (1994) Polymorphous high-grade B cell lymphoma is the predominant type of spontaneous primary cerebral malignant lymphomas. Histological and immunomorphological evaluation of computed tomography-guided stereotactic brain biopsies. Am J Surg Pathol 18(9):931–937

    Article  CAS  PubMed  Google Scholar 

  27. Scott BJ, Douglas VC, Tihan T, Rubenstein JL, Josephson SA (2013) A systematic approach to the diagnosis of suspected central nervous system lymphoma. JAMA Neurol 1–9

  28. Bühring U, Herrlinger U, Krings T, Thiex R, Weller M, Küker W (2001) MRI features of primary central nervous system lymphomas at presentation. Neurology 57(3):393–396

    Article  PubMed  Google Scholar 

  29. Schlegel U, Schmidt-Wolf IG, Deckert M (2000) Primary CNS lymphoma: clinical presentation, pathological classification, molecular pathogenesis and treatment. J Neurol Sci 181(1–2):1–12

    Article  CAS  PubMed  Google Scholar 

  30. Ferreri AJM, Blay J-Y, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell’Oro S, Zucca E, Cavalli F (2003) Prognostic scoring system for primary CNS lymphomas: The international extranodal lymphoma study group experience. J Clin Oncol 21(2):266–272

    Article  PubMed  Google Scholar 

  31. Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP, Trevor J, Glaser MG, Lantos P, Ironside JW, Moss TH, Brada M, Whaley JB, Stenning SP (2000) A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: Cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 89(6):1359–1370

    Article  CAS  PubMed  Google Scholar 

  32. Bellinzona M, Roser F, Ostertag H, Gaab RM, Saini M (2005) Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: A series of 33 cases. Eur J Surg Oncol 31(1):100–105

    Article  CAS  PubMed  Google Scholar 

  33. Lee L, Crump M, Khor S, Hoch JS, Luo J, Bremner K, Krahn M, Hodgson DC (2012) Impact of rituximab on treatment outcomes of patients with diffuse large b-cell lymphoma: A population-based analysis. Br J Haematol 158(4):481–488

    Article  CAS  PubMed  Google Scholar 

  34. Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP (2012) A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood 120(6):1210–1217

    Article  CAS  PubMed  Google Scholar 

  35. Marcus R (2005) CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 105(4):1417–1423

    Article  CAS  PubMed  Google Scholar 

  36. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadi K, Bordessoule D, Ferme C, Tilly H (2010) Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood 116(12):2040–2045

    Article  CAS  PubMed  Google Scholar 

  37. Batchelor TT, Grossman SA, Mikkelsen T, Ye X, Desideri S, Lesser GJ (2011) Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology 76(10):929–930

    Article  CAS  PubMed  Google Scholar 

  38. Fritsch K, Kasenda B, Hader C, Nikkhah G, Prinz M, Haug V, Haug S, Ihorst G, Finke J, Illerhaus G (2011) Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol 22(9):2080–2085

    Article  CAS  PubMed  Google Scholar 

  39. DeAngelis LM (2011) Radiotherapy: Has the role of WBRT in primary CNS lymphoma been settled? Nat Rev Clin Oncol 8(4):196–198

    Article  PubMed  Google Scholar 

  40. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M (2010) High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): A phase 3, randomised, non-inferiority trial. The Lancet Oncology 11(11):1036–1047

    Article  CAS  PubMed  Google Scholar 

  41. Pels H, Schmidt-Wolf IGH, Glasmacher A, Schulz H, Engert A, Diehl V, Zellner A, Schackert G, Reichmann H, Kroschinsky F, Vogt-Schaden M, Egerer G, Bode U, Schaller C, Deckert M, Fimmers R, Helmstaedter C, Atasoy A, Klockgether T, Schlegel U (2003) Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 21(24):4489–4495

    Article  CAS  PubMed  Google Scholar 

  42. Baumgartner JE, Rachlin JR, Beckstead JH, Meeker TC, Levy RM, Wara WM, Rosenblum ML (1990) Primary central nervous system lymphomas: Natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome. J Neurosurg 73(2):206–211

    Article  CAS  PubMed  Google Scholar 

  43. Kawakami Y, Tabuchi K, Ohnishi R, Asari S, Nishimoto A (1985) Primary central nervous system lymphoma. J Neurosurg 62(4):522–527

    Article  CAS  PubMed  Google Scholar 

  44. Sawaya R, Hammoud M, Schoppa D, Hess KR, Wu SZ, Shi WM, Wildrick DM (1998) Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery 42(5):1044–1055, discussion 1055–1056

    Article  CAS  PubMed  Google Scholar 

  45. McGovern PC, Lautenbach E, Brennan PJ, Lustig RA, Fishman NO (2003) Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clin Infect Dis 36(6):759–765

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert G. Kellogg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kellogg, R.G., Straus, D.C., Karmali, R. et al. Impact of therapeutic regimen and clinical presentation on overall survival in CNS lymphoma. Acta Neurochir 156, 355–365 (2014). https://doi.org/10.1007/s00701-013-1878-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-013-1878-7

Keywords

Navigation