Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma

  • Lee, Tae Hoon (Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Lee, Joo Ho (Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Chang, Ji Hyun (Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Ye, Sung-Joon (Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Tae Min (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Park, Chul-Kee (Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Il Han (Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Byoung Hyuck (Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center) ;
  • Wee, Chan Woo (Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center)
  • Received : 2020.01.29
  • Accepted : 2020.03.18
  • Published : 2020.03.31
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Abstract

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

Keywords

References

  1. Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. 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 2006;24:4570-4. https://doi.org/10.1200/JCO.2006.06.6910
  2. Kim BH, Kim IH, Park SH, et al. Low-dose whole brain radiotherapy with tumor bed boost after methotrexate-based chemotherapy for primary central nervous system lymphoma. Cancer Res Treat 2014;46:261-9. https://doi.org/10.4143/crt.2014.46.3.261
  3. Korfel A, Thiel E, Martus P, et al. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology 2015;84:1242-8. https://doi.org/10.1212/WNL.0000000000001395
  4. 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:e510-e523. https://doi.org/10.1016/S2352-3026(17)30174-6
  5. 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 Clin Oncol 2019;37:823-33. https://doi.org/10.1200/JCO.18.00306
  6. 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 Clin Oncol 2013;31:3971-9. https://doi.org/10.1200/JCO.2013.50.4910
  7. Koh HK, Kim IH, Kim TM, et al. Role of radiation therapy in primary central nervous system lymphoma : KROG 14-20 Collaborative Study of Brain and Lymphoma Committee. J Neurooncol 2017;135:629-38. https://doi.org/10.1007/s11060-017-2616-4
  8. 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. https://doi.org/10.1200/JCO.2002.11.013
  9. Abrey LE, Batchelor TT, Ferreri AJ, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 2005;23:5034-43. https://doi.org/10.1200/JCO.2005.13.524
  10. Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 2007;25:4730-5. https://doi.org/10.1200/JCO.2007.12.5062
  11. Bessell EM, Lopez-Guillermo A, Villa 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 Clin Oncol 2002;20:231-6. https://doi.org/10.1200/JCO.20.1.231
  12. Grommes C, DeAngelis LM. Primary CNS lymphoma. J Clin Oncol 2017;35:2410-8. https://doi.org/10.1200/JCO.2017.72.7602
  13. Park JS, Lim DH, Ahn YC, et al. Whole brain radiation dose reduction for primary central nervous system lymphoma patients who achieved partial response after high-dose methotrexate based chemotherapy. Jpn J Clin Oncol 2017;47:995-1001. https://doi.org/10.1093/jjco/hyx120
  14. Sheu T, Milgrom SA, Andraos TY, et al. Response-adapted radiation therapy for newly diagnosed primary diffuse large B-cell lymphoma of the CNS treated with methotrexate-based systemic therapy. Adv Radiat Oncol 2018;3:639-46. https://doi.org/10.1016/j.adro.2018.07.001
  15. Kasenda B, Loeffler J, Illerhaus G, Ferreri AJ, Rubenstein J, Batchelor TT. The role of whole brain radiation in primary CNS lymphoma. Blood 2016;128:32-6.
  16. Omuro AM, Ben-Porat LS, Panageas KS, et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol 2005;62:1595-600. https://doi.org/10.1001/archneur.62.10.1595
  17. Tofilon PJ, Fike JR. The radioresponse of the central nervous system: a dynamic process. Radiat Res 2000;153:357-70. https://doi.org/10.1667/0033-7587(2000)153[0357:TROTCN]2.0.CO;2
  18. Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 2014;32:3810-6. https://doi.org/10.1200/JCO.2014.57.2909
  19. Kazda T, Jancalek R, Pospisil P, et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol 2014;9:139. https://doi.org/10.1186/1748-717X-9-139
  20. 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. https://doi.org/10.1016/S1470-2045(10)70229-1
  21. Zimmermann M, Oehler C, Mey U, Ghadjar P, Zwahlen DR. Radiotherapy for non-Hodgkin's lymphoma: still standard practice and not an outdated treatment option. Radiat Oncol 2016;11:110. https://doi.org/10.1186/s13014-016-0690-y
  22. Kasenda B, Ferreri AJ, Marturano E, et al. First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL): a systematic review and individual patient data meta-analysis. Ann Oncol 2015;26:1305-13. https://doi.org/10.1093/annonc/mdv076
  23. 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. Cancer 2003;97:128-33. https://doi.org/10.1002/cncr.11035
  24. Omuro A, Taillandier L, Chinot O, et al. Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be deferred? J Neurooncol 2011;104:323-30. https://doi.org/10.1007/s11060-010-0497-x

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