Primary Central Nervous System Lymphoma
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Primary central nervous system lymphoma (PCNSL) comprises approximately 5 % of all primary brain tumors. During the past two decades the incidence of PCNSL has increased, and as a result clinical research to determine the optimal treatment for PCNSL patients also has increased. Diagnosis is based on histopathologic findings traditionally established by biopsy only. More recent data raise controversy and challenges this biopsy-only paradigm, showing a potential advantage for surgical resection with progression-free survival (PFS) and overall survival (OS). Using high-dose intravenous (IV) methotrexate-based chemotherapy alone or as part of a regimen can lead to disease cure. The role of whole brain radiotherapy (WBRT) remains controversial and more frequently is omitted to avoid potential delayed neurocognitive effects, especially in patients older than age 60 years. Newer data from Memorial Sloan Kettering Cancer Center (MSKCC) using five cycles of Rituximab, Methotrexate, Vincristine, and Procarbazine (R-MVP) followed by low-dose WBRT (2,340 cgy), and then two cycles of Ara-C had excellent disease control with low neuro-toxicity and is now the basis of an ongoing RTOG (Radiation Treatment Oncology Group) trial comparing early versus delayed WBRT. Other chemotherapeutics and novel treatments, such as autologous stem cell transplantation, are being studied for potential use in PCNSL. Unlike many other primary brain tumors seen in adults, PCNSL is potentially curable; therefore, balancing treatment decisions with long-term neurocognitive effects and toxicities is crucial.
KeywordsPrimary CNS lymphoma Immunocompetent Chemotherapy Methotrexate Cytarabine Rituximab Temozolomide Topotecan Pemetrexed Salvage therapy Elderly Autologous stem-cell transplantation Whole-brain radiotherapy
Stephane Doucet has received a scholarship from the CHUM Hospital Foundation. Both authors contributed equally to the manuscript.
Conflicts of Interest
Stephane Doucet declares no conflicts of interest.
Priya Kumthekar declares no conflicts of interest.
Jeffrey Raizer has board membership and stock options with Aurasense, is a consultant to Geron, received honoraria from Genentech/Roche and Novartis, received payment for development of educational presentations from Genentech/Roche.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Kluin P, Deckert M, Ferry J. Primary diffuse large B-cell lymphoma of the CNS. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 240–1.Google Scholar
- 3.National Cancer Institute. Surveillance epidemiology and end results. SEER Stat Fact Sheets: Lymphoma. Available at http://seer.cancer.gov/csr/1975_2009_pops09/results_single/sect_01_table.01.pdf. Accessed January 2013.
- 4.•Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol. 2012;14 Suppl 5:v1–49. This study provides the latest epidemiological data on Central Nervous System Tumors in the United States.PubMedCrossRefGoogle Scholar
- 7.Nakamura S, Jaffe ES, Swerdlow SH. EBV positive diffuse large B-cell lymphoma of the elderly. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 243–4.Google Scholar
- 10.Deckert M, Paulus W. Malignant lymphoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. The 2007 WHO classification of tumours of the central nervous system. Lyon: IARC; 2007.Google Scholar
- 18.•Weller M, Martus P, Roth P, Thiel E, Korfel A: Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol 2012. This retrospective study from the G-PCNSL-SG-1 challenges the old paradigm of the futility of surgery in PCNSL, but has not yet changes the recommandation of stereotactic biopsy for diagnosis of PCNSL.Google Scholar
- 24.••Ferreri AJ, Reni M, Foppoli M, 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;374:1512–20. This study is one of the three randomized study for the treatment of PCNSL. High dose Cytarabine has now been adopted as part of standard of care for the front-line treatment of PCNSL.PubMedCrossRefGoogle Scholar
- 25.••Thiel E, Korfel A, Martus P, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010;11:1036–47. It is the largest prospective randomized study on PCNSL. It suggested that omission of WBRT in first-line setting might not compromise survival, but their primary hypothesis of non inferiority was not proven.PubMedCrossRefGoogle Scholar
- 33.Larouche J-F, Bergeron M, Hampson G, Illidge T, Delage R. Rituximab Cerebrospinal fluid levels in patients with primary central nervous system lymphoma treated with intravenous high dose rituximab [abtract 1644]. Presented at the 53rd ASH Annual meeting and Exposition. San Diego, USA; December 10-13, 2011.Google Scholar
- 36.•Birnbaum T, Stadler EA, von Baumgarten L, Straube A. Rituximab significantly improves complete response rate in patients with primary CNS lymphoma. J Neurooncol. 2012;109:285–91. This is a retrospective single-center trial suggesting a significant increase in complete remission when Rituximab is use with combination chemotherapy in first-line setting.PubMedCrossRefGoogle Scholar
- 52.Raizer J, DeAngelis L, Zelenetz A, Abrey L. Activity of rituximab in primary central nervous system lymphoma PCNSL. [abstract 642]. Presented at the 2000 ASCO Annual Meeting. New Orleans, USA; May 20-23, 2000.Google Scholar
- 53.Batchelor T, Lesser G, Grossman S. Rituximab monotherapy for relapsed or refractory primary central nervous system lymphoma [abstract 2043]. Presented at the 2008 ASCO Annual Meeting. Chicago, USA; May 28 - June3, 2008.Google Scholar
- 54.••Welch MR, Omuro A, Deangelis LM. Outcomes of the oldest patients with primary CNS lymphoma treated at Memorial Sloan-Kettering Cancer Center. Neuro Oncol. 2012;14:1304–11. This study suggest that even in patient over the age 80, HD-MTX based chemotherapy is relatively well tolerated and possible.PubMedCrossRefGoogle Scholar
- 60.Soussain C, Hoang-Xuan K, Taillandier L, et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008;26:2512–8.PubMedCrossRefGoogle Scholar