Abstract：Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma that occurs in the brain, spinal cord, meninges or eyes. Diffuse large B-cell lymphoma accounts for the vast majority, of which non-GCB subtype is more common. The median survival time of untreated patients is only 3 months. Surgical removal of the tumor alone has no obvious survival benefit. Early single use of whole brain radiation therapy (WBRT) yields a high remission rate, but the duration is short, and delayed neurotoxicity is an important complication, especially for elderly patients. Subsequent studies found that high-dose methotrexate-based chemotherapy combined with WBRT significantly improved the prognosis of this disease. However, combination therapy increases the risk of neurotoxicity, and this strategy has been questioned. In recent years, reduced-dose WBRT and autologous hematopoietic stem cell transplantation have gradually replaced the previous standard-dose WBRT. This article reviews the progress on the radiotherapy for PCNSL.
Li Panpan,Zhang Zhuo. Progress on radiotherapy of primary central nervous system lymphoma[J]. Chinese Journal of Radiation Oncology, 2022, 31(5): 473-477.
[1] Ostrom QT, Cioffi G, Waite K, et al. CBTRUS statistical report:primary brain and other central nervous system tumors diagnosed in the united states in 2014-2018[J]. Neuro Oncol, 2021, 23(12 suppl 2):Ⅲ1-Ⅲ105. DOI:10.1093/neuonc/noab200. [2] Shibamoto Y, Hayabuchi N, Hiratsuka J, et al. Is whole-brain irradiation necessary for primary central nervous system lymphoma? Patterns of recurrence after partial-brain irradiation.[J]. Cancer, 2003,97(1):128-133. DOI:10.1002/cncr.11035. [3] Ferreri AJ, Blay JY, Reni M, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas[J]. Ann Oncol, 2002, 13(4):531-538. DOI:10.1093/annonc/mdf080. [4] Nelson DF, Martz KL, Bonner H, 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[J]. Int J Radiat Oncol Biol Phys, 1992, 23(1):9-17. DOI:10.1016/0360-3016(92)90538-s. [5] Taguchi S, Hamamoto Y, FujII T, et al. Prognosis of primary central nervous system lymphoma treated with radiotherapy alone[J]. Jpn J Radiol, 2012, 30(10):806-810. DOI:10.1007/s11604-012-0124-1. [6] Lachance DH, Brizel DM, Gockerman JP, et al. Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma:short-duration response and multifocal intracerebral recurrence preceding radiotherapy[J]. Neurology, 1994, 44(9):1721-1727. DOI:10.1212/wnl.44.9.1721. [7] Mead GM, Bleehen NM, Gregor A, et al. 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.[J]. Cancer, 2000,89(6):1359-1370. DOI:10.1002/1097-0142(20000915)89:6<1359::aid-cncr21>3.3.co;2-0. [8] DeAngelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma[J]. J Clin Oncol, 1992, 10(4):635-643. DOI:10.1200/JCO.1992.10.4.635. [9] DeAngelis LM, Seiferheld W, Schold SC, et al. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma:radiation therapy oncology group study 93-10[J]. J Clin Oncol, 2002, 20(24):4643-4648. DOI:10.1200/JCO.2002.11.013. [10] Ferreri AJ, Cwynarski K, Pulczynski E, et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma:results of the first randomisation of the international extranodal lymphoma study group-32(IELSG32) phase 2 trial[J]. Lancet Haematol, 2016, 3(5):e217-227. DOI:10.1016/S2352-3026(16)00036-3. [11] Wang XX, Huang HQ, Bai B, et al. Clinical outcomes of patients with newly diagnosed primary central nervous system lymphoma are comparable on treatment with high-dose methotrexate plus temozolomide and with high-dose methotrexate plus cytarabine:a single-institution experience[J]. Leuk Lymphoma, 2014, 55(11):2497-2501. DOI:10.3109/10428194.2014.889823. [12] 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[J]. Lancet, 2009, 374(9700):1512-1520. DOI:10.1016/S0140-6736(09)61416-1. [13] Reni M, Ferreri AJ, Garancini MP, et al. Therapeutic management of primary central nervous system lymphoma in immunocompetent patients:results of a critical review of the literature[J]. Ann Oncol, 1997, 8(3):227-234. DOI:10.1023/a:1008201717089. [14] Ferreri AJ, Reni M, Villa E. Therapeutic management of primary central nervous system lymphoma:lessons from prospective trials[J]. Ann Oncol, 2000, 11(8):927-937. DOI:10.1023/a:1008376412784. [15] Herrlinger U, Schäfer N, Fimmers R, et al. Early whole brain radiotherapy in primary CNS lymphoma:negative impact on quality of life in the randomized G-PCNSL-SG1 trial[J]. J Cancer Res Clin Oncol, 2017, 143(9):1815-1821. DOI:10.1007/s00432-017-2423-5. [16] Correa DD, Shi W, Abrey LE, et al. Cognitive functions in primary CNS lymphoma after single or combined modality regimens[J]. Neuro Oncol, 2012, 14(1):101-108. DOI:10.1093/neuonc/nor186. [17] 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[J]. Lancet Oncol, 2010, 11(11):1036-1047. DOI:10.1016/S1470-2045(10)70229-1. [18] Omuro A, Taillandier L, Chinot O, et al. Primary CNS lymphoma in patients younger than 60:can whole-brain radiotherapy be deferred?[J]. J Neurooncol, 2011, 104(1):323-330. DOI:10.1007/s11060-010-0497-x. [19] Ferreri A, Cwynarski K, Pulczynski E, et al. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma:results of the second randomisation of the international extranodal lymphoma study group-32 phase 2 trial[J]. Lancet Haematol, 2017, 4(11):e510-e523. DOI:10.1016/S2352-3026(17)30174-6. [20] Houillier C, Taillandier L, Dureau S, et al. Radiotherapy or autologous stem-cell transplantation for primary CNS lymphoma in patients 60 years of age and younger:results of the intergroup ANOCEF-GOELAMS randomized phase Ⅱ PRECIS study[J]. J Clin Oncol, 2019, 37(10):823-833. DOI:10.1200/JCO.18.00306. [21] Langner-Lemercier S, Houillier C, Soussain C, et al. Primary CNS lymphoma at first relapse/progression:characteristics, management, and outcome of 256 patients from the french LOC network[J]. Neuro Oncol, 2016, 18(9):1297-1303. DOI:10.1093/ neuonc/now033. [22] Muirhead R, Murray EC, Bell SL, et al. Is there a role for radiotherapy in the primary management of primary central nervous system lymphoma? A single-centre case series[J]. Clin Oncol (R Coll Radiol), 2013, 25(7):400-405. DOI:10.1016/j.clon.2013.04.007. [23] Hottinger AF, DeAngelis LM, Yahalom J, et al. Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma.[J]. Neurology, 2007,69(11):1178-1182. DOI:10.1212/01.wnl.0000276986.19602.c1. [24] Nguyen PL, Chakravarti A, Finkelstein DM, et al. Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma[J]. J Clin Oncol, 2005, 23(7):1507-1513. DOI:10.1200/JCO.2005.01.161. [25] Kim N, Lim DH, Yoon SE, et al. Selective salvage radiotherapy could provide favorable outcomes in patients with refractory or relapsed primary central nervous system lymphoma[J]. J Neurooncol, 2022, 156(2):307-316. DOI:10.1007/s11060-021-03909-1. [26] Bessell EM, López-Guillermo A, Villá S, et al. Importance of radiotherapy in the outcome of patients with primary CNS lymphoma:an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments[J]. J Clin Oncol, 2002, 20(1):231-236. DOI:10.1200/JCO.2002.20.1.231. [27] Ferreri AJ, Verona C, Politi LS, et al. Consolidation radiotherapy in primary central nervous system lymphomas:impact on outcome of different fields and doses in patients in complete remission after upfront chemotherapy[J]. Int J Radiat Oncol Biol Phys, 2011, 80(1):169-175. DOI:10.1016/j.ijrobp.2010.01.066. [28] Morris PG, Correa DD, Yahalom J, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma:final results and long-term outcome[J]. J Clin Oncol, 2013, 31(31):3971-3979. DOI:10.1200/JCO.2013.50.4910. [29] Omuro AMP, DeAngelis LM, Karrison T, et al. Randomized phase Ⅱ study of rituximab, methotrexate (MTX), procarbazine, vincristine, and cytarabine (R-MPV-A) with and without low-dose whole-brain radiotherapy (LD-WBRT) for newly diagnosed primary CNS lymphoma (PCNSL).[J]. Journal of Clinical Oncology, 2020,38(15_suppl):2501. DOI:10.1200/JCO.2020.38.15_suppl.2501. [30] Fisher B, Seiferheld W, Schultz C, et al. Secondary analysis of radiation therapy oncology group study (RTOG) 9310:an intergroup phase Ⅱ combined modality treatment of primary central nervous system lymphoma[J]. J Neurooncol, 2005, 74(2):201-205. DOI:10.1007/s11060-004-6596-9. [31] Glass J, Won M, Schultz CJ, et al. Phase I and Ⅱ study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma:NRG oncology RTOG 0227[J]. J Clin Oncol, 2016, 34(14):1620-1625. DOI:10.1200/JCO.2015.64.8634. [32] Kenai H, Yamashita M, Nakamura T, et al. Gamma knife surgery for primary central nervous system lymphoma:usefulness as palliative local tumor control[J]. J Neurosurg, 2006, 105 suppl:133-138. DOI:10.3171/sup.2006.105.7.133. [33] Palmer JD, Bhamidipati D, Shukla G, et al. Outcomes after stereotactic radiosurgery for CNS lymphoma[J]. J Neurooncol, 2020, 147(2):465-476. DOI:10.1007/s11060-020-03444-5. [34] Shin SM, Silverman JS, Bowden G, et al. Relapsed or refractory primary central nervous system lymphoma radiosurgery:report of the international gamma knife research foundation[J]. J Radiosurg SBRT, 2017, 4(4):247-253. [35] Kumar R, Laack N, Pollock BE, et al. Stereotactic radiosurgery in the treatment of recurrent CNS lymphoma[J]. World Neurosurg, 2015, 84(2):390-397. DOI:10.1016/j.wneu.2015.03.062.
2022, Vol. 31 
