Journal of Clinical Oncology, Vol 10, 635-643, Copyright © 1992 by American Society of Clinical Oncology

ARTICLES

Combined modality therapy for primary CNS lymphoma

LM DeAngelis, J Yahalom, HT Thaler and U Kher
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

PURPOSE: Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non- AIDS PCNSL. PATIENTS AND METHODS: Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS: Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION: The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. Angelov, N. D. Doolittle, D. F. Kraemer, T. Siegal, G. H. Barnett, D. M. Peereboom, G. Stevens, J. McGregor, K. Jahnke, C. A. Lacy, et al. Blood-Brain Barrier Disruption and Intra-Arterial Methotrexate-Based Therapy for Newly Diagnosed Primary CNS Lymphoma: A Multi-Institutional Experience J. Clin. Oncol., July 20, 2009; 27(21): 3503 - 3509. [Abstract] [Full Text] [PDF]

				M. Sierra del Rio, A. Rousseau, C. Soussain, D. Ricard, and K. Hoang-Xuan Primary CNS Lymphoma in Immunocompetent Patients Oncologist, May 1, 2009; 14(5): 526 - 539. [Abstract] [Full Text] [PDF]

				G. Illerhaus, R. Marks, F. Muller, G. Ihorst, F. Feuerhake, M. Deckert, C. Ostertag, and J. Finke High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study Ann. Onc., February 1, 2009; 20(2): 319 - 325. [Abstract] [Full Text] [PDF]

				S. A. Grimm, C. A. McCannel, A.M.P. Omuro, A. J.M. Ferreri, J. -Y. Blay, E. A. Neuwelt, T. Siegal, T. Batchelor, K. Jahnke, T. N. Shenkier, et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report Neurology, October 21, 2008; 71(17): 1355 - 1360. [Abstract] [Full Text] [PDF]

				R. Yamanaka, K. Morii, Y. Shinbo, J. Homma, M. Sano, N. Tsuchiya, N. Yajima, T. Tamura, H. Hondoh, H. Takahashi, et al. Results of Treatment of 112 Cases of Primary CNS Lymphoma Jpn. J. Clin. Oncol., May 1, 2008; 38(5): 373 - 380. [Abstract] [Full Text] [PDF]

				N. A. Mohile, L. M. DeAngelis, and L. E. Abrey The utility of body FDG PET in staging primary central nervous system lymphoma Neuro-oncol, April 1, 2008; 10(2): 223 - 228. [Abstract] [Full Text] [PDF]

				M Montemurro, T Kiefer, F Schuler, H. Al-Ali, H-H Wolf, R Herbst, A Haas, K Helke, A Theilig, C Lotze, et al. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study Ann. Onc., April 1, 2007; 18(4): 665 - 671. [Abstract] [Full Text] [PDF]

				A. Lobo, N. Okhravi, P. Adamson, B. J Clark, and S. Lightman Protocol for the Use of Polymerase Chain Reaction in the Detection of Intraocular Large B-Cell Lymphoma in Ocular Samples J. Mol. Diagn., February 1, 2007; 9(1): 113 - 121. [Abstract] [Full Text] [PDF]

				E. T. Wong Management of Central Nervous System Lymphomas Using Monoclonal Antibodies: Challenges and Opportunities Clin. Cancer Res., October 1, 2005; 11(19): 7151s - 7157s. [Abstract] [Full Text] [PDF]

				L. E. Abrey, T. T. Batchelor, A. J.M. Ferreri, M. Gospodarowicz, E. J. Pulczynski, E. Zucca, J. R. Smith, A. Korfel, C. Soussain, L. M. DeAngelis, et al. Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS Lymphoma J. Clin. Oncol., August 1, 2005; 23(22): 5034 - 5043. [Abstract] [Full Text] [PDF]

				A. M.P. Omuro, L. M. DeAngelis, J. Yahalom, and L. E. Abrey Chemoradiotherapy for primary CNS lymphoma: An intent-to-treat analysis with complete follow-up Neurology, January 11, 2005; 64(1): 69 - 74. [Abstract] [Full Text] [PDF]

				L. Fischer, E. Thiel, H. A. Klasen, H. Kirchen, K. Jahnke, and A. Korfel Response of relapsed or refractory primary central nervous system lymphoma (PCNSL) to topotecan Neurology, May 25, 2004; 62(10): 1885 - 1887. [Abstract] [Full Text] [PDF]

				H. Harder, H. Holtel, J. E.C. Bromberg, P. Poortmans, H. Haaxma-Reiche, H. C. Kluin-Nelemans, J. Menten, and M. J. van den Bent Cognitive status and quality of life after treatment for primary CNS lymphoma Neurology, February 24, 2004; 62(4): 544 - 547. [Abstract] [Full Text] [PDF]

				D. D. Correa, L. M. DeAngelis, W. Shi, H. Thaler, A. Glass, and L. E. Abrey Cognitive functions in survivors of primary central nervous system lymphoma Neurology, February 24, 2004; 62(4): 548 - 555. [Abstract] [Full Text] [PDF]

				H. Pels, I. G.H. Schmidt-Wolf, A. Glasmacher, H. Schulz, A. Engert, V. Diehl, A. Zellner, G. Schackert, H. Reichmann, F. Kroschinsky, et al. Primary Central Nervous System Lymphoma: Results of a Pilot and Phase II Study of Systemic and Intraventricular Chemotherapy With Deferred Radiotherapy J. Clin. Oncol., December 15, 2003; 21(24): 4489 - 4495. [Abstract] [Full Text] [PDF]

				V. S. Lima, E. B. Leite, R. P. Fonseca, and A. S. Fernandes Jr Patients Presenting With CNS Lesions: CASE 1. PRIMARY LOW-GRADE MUCOSA-ASSOCIATED B-CELL LYMPHOMA OF THE DURA J. Clin. Oncol., November 1, 2003; 21(21): 4058 - 4060. [Full Text] [PDF]

				H. Ishikawa, M. Hasegawa, Y. Tamaki, K. Hayakawa, T. Akimoto, H. Sakurai, N. Mitsuhashi, H. Niibe, M. Tamura, and T. Nakano Comparable Outcomes of Radiation Therapy without High-dose Methotrexate for Patients with Primary Central Nervous System Lymphoma Jpn. J. Clin. Oncol., September 1, 2003; 33(9): 443 - 449. [Abstract] [Full Text] [PDF]

				K. Hoang-Xuan, L. Taillandier, O. Chinot, P. Soubeyran, U. Bogdhan, J. Hildebrand, M. Frenay, N. De Beule, J.Y. Delattre, and B. Baron Chemotherapy Alone as Initial Treatment for Primary CNS Lymphoma in Patients Older Than 60 Years: A Multicenter Phase II Study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group J. Clin. Oncol., July 15, 2003; 21(14): 2726 - 2731. [Abstract] [Full Text] [PDF]

				K. Fliessbach, H. Urbach, C. Helmstaedter, H. Pels, A. Glasmacher, J. A. Kraus, T. Klockgether, I. Schmidt-Wolf, and U. Schlegel Cognitive Performance and Magnetic Resonance Imaging Findings After High-Dose Systemic and Intraventricular Chemotherapy for Primary Central Nervous System Lymphoma Arch Neurol, April 1, 2003; 60(4): 563 - 568. [Abstract] [Full Text] [PDF]

				L. M. DeAngelis, W. Seiferheld, S. C. Schold, B. Fisher, and C. J. Schultz Combination Chemotherapy and Radiotherapy for Primary Central Nervous System Lymphoma: Radiation Therapy Oncology Group Study 93-10 J. Clin. Oncol., December 15, 2002; 20(24): 4643 - 4648. [Abstract] [Full Text] [PDF]

				A multicenter study of treatment of primary CNS lymphoma Neurology, May 28, 2002; 58(10): 1513 - 1520.

				P N Shams, A Waldman, and G T Plant B Cell lymphoma of the brain stem masquerading as myasthenia J. Neurol. Neurosurg. Psychiatry, February 1, 2002; 72(2): 271 - 273. [Abstract] [Full Text] [PDF]

				A. Lister, L. E. Abrey, and J. T. Sandlund Central Nervous System Lymphoma Hematology, January 1, 2002; 2002(1): 283 - 296. [Abstract] [Full Text]

				L Ayuso-Peralta, M Orti-Pareja, M Zurdo-Hernandez, F J Jimenez-Jimenez, J Tejeiro-Martinez, J R Ricoy, A de la Lama, and A I Bernardo Cerebral lymphoma presenting as a leukoencephalopathy J. Neurol. Neurosurg. Psychiatry, August 1, 2001; 71(2): 243 - 246. [Abstract] [Full Text] [PDF]

				U Schlegel, H Pels, A Glasmacher, R Kleinschmidt, I Schmidt-Wolf, C Helmstaedter, K Fliessbach, M Deckert, D Van Roost, R Fimmers, et al. Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study J. Neurol. Neurosurg. Psychiatry, July 1, 2001; 71(1): 118 - 122. [Abstract] [Full Text] [PDF]

				J. Hochman, N. Assaf, M. Deckert-Schluter, O. D. Wiestler, and J. Pe'er Entry Routes of Malignant Lymphoma into the Brain and Eyes in a Mouse Model Cancer Res., July 1, 2001; 61(13): 5242 - 5247. [Abstract] [Full Text] [PDF]

				C. Soussain, F. Suzan, K. Hoang-Xuan, N. Cassoux, V. Levy, N. Azar, C. Belanger, E. Achour, V. Ribrag, S. Gerber, et al. Results of Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue in 22 Patients With Refractory or Recurrent Primary CNS Lymphoma or Intraocular Lymphoma J. Clin. Oncol., February 1, 2001; 19(3): 742 - 749. [Abstract] [Full Text] [PDF]

				N. D. Doolittle, C. P. Anderson, W. A. Bleyer, J. G. Cairncross, T. Cloughesy, S. L. Eck, P. Guastadisegni, W. A. Hall, L. L. Muldoon, S. J. Patel, et al. Importance of dose intensity in neurooncology clinical trials: Summary Report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium Neuro-oncol, January 1, 2001; 3(1): 46 - 54. [Abstract] [PDF]

				M-F. Mamzer-Bruneel, C. Lome, E. Morelon, V. Levy, P. Bourquelot, F. Jacobs, A. Gessain, E. Mac Intyre, N. Brousse, H. Kreis, et al. Durable Remission After Aggressive Chemotherapy for Very Late Post-Kidney Transplant Lymphoproliferation: A Report of 16 Cases Observed in a Single Center J. Clin. Oncol., November 1, 2000; 18(21): 3622 - 3632. [Abstract] [Full Text] [PDF]

				C. Cursiefen, L. M. Holbach, B. Lafaut, K. Heimann, T. Kirchner, and G. O. H. Naumann Oculocerebral Non-Hodgkin's Lymphoma With Uveal Involvement: Development of an Epibulbar Tumor After Vitrectomy Arch Ophthalmol, October 1, 2000; 118(10): 1437 - 1440. [Abstract] [Full Text] [PDF]

				L. E. Abrey, J. Yahalom, and L. M. DeAngelis Treatment for Primary CNS Lymphoma: The Next Step J. Clin. Oncol., September 17, 2000; 18(17): 3144 - 3150. [Abstract] [Full Text] [PDF]

				U. Herrlinger, W. Brugger, M. Bamberg, W. Kuker, J. Dichgans, and M. Weller PCV salvage chemotherapy for recurrent primary CNS lymphoma Neurology, April 25, 2000; 54(8): 1707 - 1708. [Full Text] [PDF]

				H. A. Fine, W. D. Figg, K. Jaeckle, P. Y. Wen, A. P. Kyritsis, J. S. Loeffler, V. A. Levin, P. M. Black, R. Kaplan, J. M. Pluda, et al. Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients With Recurrent High-Grade Gliomas J. Clin. Oncol., February 14, 2000; 18(4): 708 - 708. [Abstract] [Full Text] [PDF]

				S. Ng, M. A. Rosenthal, D. Ashley, and L. Cher High-dose methotrexate for primary CNS lymphoma in the elderly Neuro-oncol, January 1, 2000; 2(1): 40 - 44. [Abstract] [PDF]

				L. M DeANGELIS Primary central nervous system lymphoma J. Neurol. Neurosurg. Psychiatry, June 1, 1999; 66(6): 699 - 701. [Full Text]

				M. D de Smet, V. S. Vancs, D. Kohler, D. Solomon, and C. C. Chan Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma Br J Ophthalmol, April 1, 1999; 83(4): 448 - 451. [Abstract] [Full Text]

				S. M. Whitcup, V. Stark-Vancs, R. E. Wittes, D. Solomon, M. J. Podgor, R. B. Nussenblatt, and C.-C. Chan Association of Interleukin 10 in the Vitreous and Cerebrospinal Fluid and Primary Central Nervous System Lymphoma Arch Ophthalmol, September 1, 1997; 115(9): 1157 - 1160. [Abstract] [PDF]