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Innovative Therapeutic Strategies for Primary CNS Lymphoma

  • Neuro-oncology (R Soffietti, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Summary

Primary central nervous system (CNS) lymphoma (PCNSL) represents 4% of all CNS malignancies and 4–6% of all extranodal lymphomas. Its low incidence is the main reason why it has been difficult to develop guidelines on the treatment and management of PCNSL patients. The lack of consensus around standard therapy and best diagnostic approach, inevitably, affected the outcome of these patients for many years. Current efforts are focusing on: (1) defining the optimal induction and consolidation therapies in fit and frail patients, (2) establishing when and how to use the new non-cytotoxic agents, (3) investigating innovative radiotherapy to mitigate treatment-related neurotoxicity, (4) limiting delays in diagnosis, and (5) improving response assessment with new biological markers and radiological tools. Finally, the complexity of the management of PCNSL patients compels clinicians to provide timely and efficient social, neuropsychological, and physiotherapy support, which is feasible only when there is effective collaboration between the multiple specialists involved in the care of these patients.

Recent Findings

In the last decade, thanks to multicenter collaborations, important gains have been made, particularly in the front line therapy and in the biological understanding of this disease. The progressive knowledge on molecular profile of PCNSL has justified the recent use of targeted therapy also in these settings of patients.

Purpose of Review

In this review, we discuss important advances in the management of PCNSL and we highlight unresolved questions that should be addressed in the future.

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References and Recommended Reading

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  1. Deckert M, Engert A, Bruck W, et al. Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia. 2011;25:1797–807.

    CAS  PubMed  Google Scholar 

  2. Ferreri AJ, Abrey LE, Blay JY, et al. 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. 2003;21:2407–14.

    PubMed  Google Scholar 

  3. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. WHO classification of tumours, revised 4th edition, Volume 2. IARC Press; 2017.

  4. Braggio E, Van Wier S, Ojha J, et al. Genome-wide analysis uncovers novel recurrent alterations in primary central nervous system lymphomas. Clin Cancer Res. 2015;21(17):3986–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chapuy B, Roemer MG, Stewart C, et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016;127(7):869–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.

    PubMed  Google Scholar 

  7. • Schorb E, Fox CP, Kasenda B, et al. Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice. Br J Haematol. 2020;189[5]:879–887. This report underscores the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.

  8. •• Ferreri AJM, 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. Lancet Haematol. 2017;4[11]:e510-e523. This report demonstrated that WBRT and ASCT are both feasible and effective as consolidative therapies after high-dose methotrexate-based chemoimmunotherapy in PCNSL patients <70 years.

  9. 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. Omuro AM, Chinot O, Taillandier L, et al. Methotrexate and temozolomide versus methotreaxate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in the elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol. 2015;2:e251–9.

    Google Scholar 

  10. Omuro AM, Chinot O, Taillandier L, Ghesquieres H, Soussain C, Delwail V, et al. Methotrexate and temozolomide versus methotreaxate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in the elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol. 2015;2:e251–9.

    PubMed  Google Scholar 

  11. Mead GM, Bleehen NM, Gregor A, Bullimore J, Murrell DS, Rampling RP, et al. A medical research council randomized trial in patients with primary cerebral nonhodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer. 2000;89(6):1359–70.

    CAS  PubMed  Google Scholar 

  12. Ferreri AJ, Licata G, Foppoli M, et al. Clinical relevance of the dose of cytarabine in the upfront treatment of primary CNS lymphomas with methotrexate-cytarabine combination. Oncologist. 2011;16(3):336–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab [MATRix regimen] in patients with primary I international Extranodal Lymphoma Study Group-32 [IELSG32] phase 2 trial. Lancet Haematol. 2016;3(5):e217–27.

    PubMed  Google Scholar 

  14. Omuro A, Correa DD, DeAngelis LM, 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(9):1403–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, 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 Clin Oncol. 2013;31(31):3971–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. •• 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: result of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study. J Clin Oncol 2019; 37: 823–833. This report demonstrates that WBRT and ASCT are effective consolidation treatments for patients with PCNSL patients <60.

  18. Villano JL, Koshy M, Shaikh H, Dolecek TA, McCarthy BJ. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. BrJ Cancer. 2011;105:1414–8.

    CAS  Google Scholar 

  19. Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fossa A, Eriksson M, et al. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by deescalating induction and introducing temozolomide maintenance: results from a phase II study by the nordic lymphoma group. Haematologica. 2015;100:534–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, et al. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients [PRIMAIN study]. Leukemia. 2017;31:846–52.

    CAS  PubMed  Google Scholar 

  21. Rubenstein JL. Biology of CNS lymphoma and the potential of novel agents. Hematology Am Soc Hematol Educ Program. 2017;2017:556–64.

    PubMed  PubMed Central  Google Scholar 

  22. • Vu K., Mannis G., Hwang J., et al. Low-dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma. Br J Haematol, Jul 2019; 186 [1], 180–183. This report illustrated that lenalidomide maintenance is feasible and its toxicity is manageable in PCNSL patients.

  23. Korfel A, Schlegel U, Herrlinger U, Dreyling M, Schmidt C, von Baumgarten L, et al. Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma. J Clin Oncol. 2016;34:1757–63.

    CAS  PubMed  Google Scholar 

  24. • Grommes G, Gavrilovic IT, Kaley TJ, et al. Updated results of single-agent ibrutinib in recurrent/refractory primary [PCNSL] and secondary CNS lymphoma [SCNSL]. J Clin Oncol. 2017;35[suppl; abstr 7515]. 65. This report demonstrated promising results with ibrutinib in refractory/relapsed PCNSL patients.

  25. •• Grommes C, Tang SS, Wolfe J, et al. Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma. Blood. 2019;133[5]:436–445. This report demonstrated that the combination of ibrutinib, high dose methotrexate and rituximab was well tolerated with an acceptable safety profile and promising activity was observed with high clinical responses rate.

  26. • Soussain C, Choquet S, Blonski M, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association [LYSA] and the French oculo-cerebral lymphoma [LOC] network. Eur J Cancer. 2019;117:121–130. This report confirmed the clinical activity of ibrutinib in the brain, the CSF and the intraocular compartment and good tolerability in refractory/relapsed PCNSL patients.

  27. Rubenstein JL, Geng H, Fraser EJ, et al. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv. 2018;2[13]:1595–1607. 71.

  28. Ghesquieres H, Chevrier M, Laadhari M, Chinot O, Choquet S, Moluçon-Chabrot C, et al. Lenalidomide in combination with intravenous rituximab [REVRI] in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma [LOC] Network and the Lymphoma Study Association [LYSA]. Ann Oncol. 2019 Apr 1;30(4):621–8.

    CAS  PubMed  Google Scholar 

  29. Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017 Jun 8;129(23):3071–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Chan TSY, Khong PL, Au-Yeung R, Kwong YL, Tse E. Low-dose nivolumab induced durable complete response in relapsed primary central nervous system diffuse large B cell lymphoma. Ann Hematol. 2019 Sep;98(9):2227–30.

    CAS  PubMed  Google Scholar 

  31. Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21:922–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Goldwirt, L., Beccaria, K., Ple, A. et al. Ibrutinib brain distribution: a preclinical study. Cancer Chemother Pharmacol 81, 783–789 [2018].

  33. Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, et al. Ibrutinib unmasks critical role of Bruton tyrosine kinase in primary CNS lymphoma. Cancer Discov. 2017;7(9):1018–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B cell receptor signaling by Ibrutinib in primary CNS lymphoma. Cancer Cell. 2017;31[6]:833–843.e5.

  35. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF kappa B. J Clin Invest. 2001;107:241–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Houillier C, Choquet S, Touitou V, Martin-Duverneuil N, Navarro S, Mokhtari K, et al. Lenalidomide monotherapy as salvage treatment for recurrent primary CNS lymphoma. Neurology. 2015 Jan 20;84(3):325–6.

    PubMed  Google Scholar 

  37. El-Tawab R, Hamada A, Elhagracy R, et al-. Promising effect of PDL1 inhibitors in the front-line management of primary aggressive central nervous system lymphoma: A case report [published online ahead of print, 2020 Jun 30]. Hematol Oncol Stem Cell Ther. 2020;S1658–3876[20]30114-X.

  38. Graber JJ, Plato B, Mawad R, et al. Pembrolizumab immunotherapy for relapsed CNS lymphoma [published online ahead of print]. Leuk Lymphoma. 2020;2020 Mar 23:1–3.

  39. Grommes C, Nayak L, Tun HW, et al. Introduction of novel agents in the treatment of primary CNS lymphoma. Neuro-Oncology.Epub 2018 Nov 13.

  40. • Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380[1]:45–56. This report demonstrated high rates of durable responses with tisagenlecleucel in diffuse large B cell lymphoma.

  41. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. • Abramson SJ, Gordon L, Lia Palomba M, et al. Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel [JCAR017] in R/R aggressive NHL. J Clin Oncol. [2018] 36:7505. This report demonstrated the efficacy of this agent in relapsed/refractory diffuse large B cell lymphoma patients.

  43. •• Abramson JS, McGree B, Noyes S, et al. Anti-CD19 CAR T cells in CNS diffuse large-B-cell lymphoma. N Engl J Med. 2017;377[8]:783–784. This report demonstrated the activity of CAR T therapy in CNS lymphoma without increasing neurotoxicity.

  44. Frigault MJ, Dietrich J, Martinez-Lage M, Leick M, Choi BD, DeFilipp Z, et al. Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma. Blood. 2019 Sep 12;134(11):860–6.

  45. •• Novo M, Ruff MW, Skrabek PJ, et al. Axicabtagene ciloleucel chimeric antigen receptor T cell therapy in lymphoma with secondary central nervous system involvement. Mayo Clin Proc. 2019 Nov;94[11]:2361–2364. This report demonstrated that patients with CNS involvement can be treated safely with CAR-T therapy.

  46. •• Tu S, Zhou X, Guo Z. CD19 and CD70 dual-target chimeric antigen receptor T-cell therapy for the treatment of relapsed and refractory primary central nervous system diffuse large B-cell lymphoma. Front Oncol. 2019 Dec 4;9:1350. This report demonstated that CNS lymphoma is not an absolute contraindication for dual-target CAR T-cell therapy.

  47. •• Ferreri AJM, Calimeri T, Ponzoni M, et al. Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial. Blood Adv. 2020;4[15]:3648–3658. This report describes an innovative, promising therapeutic approach for CNS lymphomas with a manageable toxicity.

  48. Wang X, Liu P, Yang W, Li L, Li P, Liu Z, et al. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood-brain barrier. Int J Nanomedicine. 2014;9:4899–909.

    PubMed  PubMed Central  Google Scholar 

  49. Angelov L, Doolittle ND, Kraemer DF, Siegal T, Barnett GH, Peereboom DM, 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. 2009 Jul 20;27(21):3503–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Rubenstein JL, Li J, Chen L, Advani R, Drappatz J, Gerstner E, et al. Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood. 2013;121:745–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Muldoon LL, Alvarez JI, Begley DJ, Boado RJ, del Zoppo GJ, Doolittle ND, et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J Cereb Blood Flow Metab. 2013;33(1):13–21.

    CAS  PubMed  Google Scholar 

  52. Neuwelt EA, Bauer B, Fahlke C, Fricker G, Iadecola C, Janigro D, et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci. 2011;12(3):169–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Muldoon LL, Soussain C, Jahnke K, Johanson C, Siegal T, Smith QR, et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol. 2007;25:2295–305.

    CAS  PubMed  Google Scholar 

  54. Batchelor TT. Am Soc Hematol Educ program 2016.

    Google Scholar 

  55. Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, et al. Strategies to advance translational research into brain barriers. Lancet Neurol. 2008;7:84–96.

    CAS  PubMed  Google Scholar 

  56. Roman-Goldstein SM, Barnett PA, McCormick CI, et al. Effects of Gd-DTPA after osmotic BBB disruption in a rodent model: toxicity and MR findings. J Comput Assist Tomogr. 1994;18(5):731–6.

    CAS  PubMed  Google Scholar 

  57. Neuwelt EA, Goldman DL, Dahlborg SA, Crossen J, Ramsey F, Roman-Goldstein S, et al. Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function. J Clin Oncol. 1991 Sep;9(9):1580–90.

    CAS  PubMed  Google Scholar 

  58. Roman-Goldstein S, Mitchell P, Crossen JR, Williams PC, Tindall A, Neuwelt EA. MR and cognitive testing of patients undergoing osmotic blood-brain barrier disruption with intraarterial chemotherapy. AJNR Am J Neuroradiol. 1995 Mar;16(3):543–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, et al. Seizure-promoting effect of blood–brain barrier disruption. Epilepsia. 2007;48(4):732–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Kuitunen H, Tokola S, Siniluoto T, et al. Promising treatment results with blood brain barrier disruption [BBBD] based immunochemotherapy combined with autologous stem cell transplantation [ASCT] in patients with primary central nervous system lymphoma [PCNSL]. J Neuro-Oncol. 2016;1–8:15.

    Google Scholar 

  61. Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E. Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol. 1973;152(4):317–25.

    CAS  PubMed  Google Scholar 

  62. Doolittle ND, Anderson CP, Bleyer WA, Cairncross JG, Cloughesy T, Eck SL, et al. Importance of dose intensity in neuro-oncology clinical trials: summary report of the sixth annual meeting of the blood brain barrier disruption consortium. Neuro-Oncology. 2001 Jan;3(1):46–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Neuwelt EA, Barnett PA, McCormick CI, Remsen LG, Kroll RA, Sexton G. Differential permeability of a human brain tumor xenograft in the nude rat: impact of tumor size and method of administration on optimizing delivery of biologically diverse agents. Clin Cancer Res. 1998;4(6):1549–55.

    CAS  PubMed  Google Scholar 

  64. Mesiwala AH, Farrell L, Wenzel HJ, Silbergeld DL, Crum LA, Winn HR, et al. High-intensity focused ultrasound selectively disrupts the blood–brain barrier in vivo. Ultrasound Med Biol. 2002;28(3):389–400.

    PubMed  Google Scholar 

  65. Dubinsky TJ, Cuevas C, Dighe MK, Kolokythas O, Hwang JH. High-intensity focused ultrasound: current potential and oncologic applications. AJR Am J Roentgenol. 2008;190(1):191–9.

    PubMed  Google Scholar 

  66. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood–brain barrier in rabbits. Radiology. 2001;220(3):640–6.

    CAS  PubMed  Google Scholar 

  67. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ, Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93–10. J Clin Oncol. 2002;20:4643–8.

    PubMed  Google Scholar 

  68. Correa DD, Shi W, Abrey LE, et al. et al., Cognitive functions in primary CNS lymphoma after single or combined modality regimens. Neuro Oncol. 2012;14[1]:101–8.

  69. Doolittle ND, Korfel A, Lubow MA, Schorb E, Schlegel U, Rogowski S, et al. Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma. Neurology. 2013;81(1):84–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Tofilon PJ, Fike JR. The radio-response of the central nervous system: a dynamic process. Radiat Res. 2000;153:357–70.

    CAS  PubMed  Google Scholar 

  71. Greene-Schloesser D, Robbins ME, Peiffer AM, et al. Radiation-induced brain injury: a review. Front Oncol. 2012;2:73. Published 2012 Jul 19.

  72. • Turnquist C, Harris BT, Harris CC. Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation. Neurooncol Adv. 2020;2[1]:vdaa057. Published 2020 May 5. The pathogenesis mechanisms behind radiation-induced brain injury includes neuroinflammation and reduced hippocampal neurogenesis.

  73. DeAngelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma. J Clin Oncol. 1992;10:635–43.

    CAS  PubMed  Google Scholar 

  74. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, 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.

    CAS  PubMed  Google Scholar 

  75. Weller M. The vanishing role of whole brain radiotherapy for primary central nervous system lymphoma. Neuro-Oncology. 2014;16(8):1035–6.

    PubMed  PubMed Central  Google Scholar 

  76. Omuro AM, Ben-Porat LS, Panageas KS, Kim AK, Correa DD, Yahalom J, et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol. 2005;62(10):1595–600.

    PubMed  Google Scholar 

  77. •• Omuro A.M.P., DeAngelis M.N., 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]. Journal of Clinical Oncology 38, no. 15_suppl [May 20, 2020] 2501–2501. LD-WBRT seems to confer a long lasting disease-control with favorable neurotoxicity profile.

  78. Correa DD, Braun E, Kryza-Lacombe M, Ho KW, Reiner AS, Panageas KS, et al. Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation. J Neuro-Oncol. 2019;144(3):553–62. https://doi.org/10.1007/s11060-019-03257-1.

    Article  CAS  Google Scholar 

  79. Correa DD, Maron L, Harder H, Klein M, Armstrong CL, Calabrese P, et al. Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. Ann Oncol. 2007;18(7):1145–51.

    CAS  PubMed  Google Scholar 

  80. • van der Meulen M, Dirven L, Habets EJJ, van den Bent MJ, et al. Cognitive functioning and health-related quality of life in patients with newly diagnosed primary CNS lymphoma: a systematic review. Lancet Oncol. 2018;19[8]:e407-e418. This review reported a negative effect on HRQOL and cognition in patients with PCNSL with combined chemotherapy and radiotherapy.

  81. Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease [NCCTG N107C/CEC·3]: a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18:1049–60.

    PubMed  PubMed Central  Google Scholar 

  82. Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013;31(1):65–72.

    PubMed  Google Scholar 

  83. Martínez P, Mak RH, Oxnard GR. Targeted therapy as an alternative to whole-brain radiotherapy in EGFR-mutant or ALK-positive non-small-cell lung cancer with brain metastases. JAMA Oncol. 2017;3(9):1274–5.

    PubMed  Google Scholar 

  84. Mainwaring W, Bowers J, Pham N, Pezzi T, Shukla M, Bonnen M, et al. Stereotactic radiosurgery versus whole brain radiation therapy: a propensity score analysis and predictors of care for patients with brain metastases from breast cancer. Clin Breast Cancer. 2019;19(2):e343–51.

    PubMed  Google Scholar 

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Acknowledgements

We would like to show our gratitude to Andrés J. M. Ferreri, MD, head of Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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  1. Teresa Calimeri and Sara Steffanoni contributed equally to this work.

Authors and Affiliations

  1. Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy

    Teresa Calimeri MD, PhD & Sara Steffanoni MD

  2. Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Tracy T. Batchelor MD

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Correspondence to Sara Steffanoni MD.

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Calimeri Teresa and Sara Steffanoni declare no potential conflicts of interest. Tracy T. Batchelor reports royalties from UpToDate, Inc. and served on scientific advisory board for Genomicare.

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Calimeri, T., Steffanoni, S. & Batchelor, T.T. Innovative Therapeutic Strategies for Primary CNS Lymphoma. Curr Treat Options Neurol 23, 12 (2021). https://doi.org/10.1007/s11940-021-00668-2

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