Abstract
Introduction
We aimed to investigate the role of upfront whole-brain radiation therapy (RT), with a reduced dose of 23.4 Gy, following high-dose methotrexate (HD-MTX) in patients with primary central nervous system lymphoma (PCNSL).
Methods
We retrospectively reviewed 185 patients with PCNSL treated with HD-MTX between January 2013 and January 2020; 145 patients underwent no RT and 40 patients underwent upfront RT. Using propensity score matching (PSM) to adjust for clinical factors, 40 patients were selected from each treatment group. Event-free survival (EFS) and overall survival (OS) were compared between treatment groups.
Results
At baseline, patients in the upfront RT group were younger, had higher LDH levels, received less frequent rituximab and stem cell transplantation than those in the no-RT group. Patients in the upfront RT group also showed a lower response rate after initial HD-MTX than those in the no-RT group (73% vs. 88%, p = 0.038). The median follow-up was 25.1 (interquartile range 13.7–43.0) months. Comparable 2-year EFS and OS rates were observed between the upfront RT and no-RT groups (56.6% vs. 53.8%, p = 0.170; and 81.7% vs. 75.3%, p = 0.097, respectively). Upfront RT was related to improved EFS and OS in patients with stable disease or progressive disease after HD-MTX, but not in patients with complete or partial response after HD-MTX. Upfront RT was also an independent predictor of EFS and OS in the PSM cohort. The cumulative incidences of treatment-related neurotoxicity at 3 years were 20.2% and 21.2% in the upfront RT and no-RT groups, respectively (p = 0.630).
Conclusions
Upfront RT with a reduced dose of 23.4 Gy, showed favorable outcomes in patients with stable disease or progressive disease after initial HD-MTX. In addition, upfront RT appears to be an effective treatment for PCNSL when rituximab or stem cell transplantation is not feasible.
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It is limited due to institutional data protection law and confidentiality of patient data.
Change history
17 August 2021
A Correction to this paper has been published: https://doi.org/10.1007/s11060-021-03824-5
References
Korfel A, Schlegel U (2013) Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9:317–327. https://doi.org/10.1038/nrneurol.2013.83
Grommes C, DeAngelis LM (2017) Primary CNS lymphoma. J Clin Oncol 35:2410–2418. https://doi.org/10.1200/jco.2017.72.7602
Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M (2010) 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 11:1036–1047. https://doi.org/10.1016/s1470-2045(10)70229-1
Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G (2017) 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 4:e510–e523. https://doi.org/10.1016/s2352-3026(17)30174-6
Houillier C, Taillandier L, Dureau S, Lamy T, Laadhari M, Chinot O, Moluçon-Chabrot C, Soubeyran P, Gressin R, Choquet S, Damaj G, Thyss A, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Tanguy ML, Al Jijakli A, Morel P, Bourquard P, Moles MP, Chauchet A, Gastinne T, Constans JM, Langer A, Martin A, Moisson P, Lacomblez L, Martin-Duverneuil N, Delgadillo D, Turbiez I, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, Soussain C (2019) 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 37:823–833. https://doi.org/10.1200/jco.18.00306
Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE (2007) Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 25:4730–4735. https://doi.org/10.1200/jco.2007.12.5062
Adhikari N, Biswas A, Gogia A, Sahoo RK, Garg A, Nehra A, Sharma MC, Bhasker S, Singh M, Sreenivas V, Chawla R, Joshi G, Kumar L, Chander S (2018) A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome. J Neurooncol 139:153–166. https://doi.org/10.1007/s11060-018-2856-y
Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A (2013) 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 31:3971–3979. https://doi.org/10.1200/jco.2013.50.4910
Kim BH, Kim IH, Park SH, Park CK, Jung HW, Kim TM, Lee SH, Heo DS (2014) Low-dose whole brain radiotherapy with tumor bed boost after methotrexate-based chemotherapy for primary central nervous system lymphoma. Cancer Res Treat 46:261–269. https://doi.org/10.4143/crt.2014.46.3.261
Lee TH, Lee JH, Chang JH, Ye SJ, Kim TM, Park CK, Kim IH, Kim BH, Wee CW (2020) Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma. Radiat Oncol J 38:35–43. https://doi.org/10.3857/roj.2020.00052
Sheu T, Milgrom SA, Andraos TY, Gunther JR, Chi L, Nastoupil L, Fowler N, Oki Y, Fanale MA, Fayad LE, Hagemeister F, Neelapu SS, Medeiros LJ, Hosing C, Nieto Y, Ahmed S, Alousi AM, Dabaja B, Pinnix CC (2018) 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 3:639–646. https://doi.org/10.1016/j.adro.2018.07.001
Park JS, Lim DH, Ahn YC, Park W, Kim SJ, Kim WS, Kim K (2017) 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 47:995–1001. https://doi.org/10.1093/jjco/hyx120
Koh HK, Kim IH, Kim TM, Lim DH, Oh D, Cho JH, Kim WC, Kim JH, Chung WK, Jeong BK, Kang KM, Hong S, Suh CO, Kim IA (2017) Role of radiation therapy in primary central nervous system lymphoma: KROG 14–20 Collaborative Study of Brain and Lymphoma Committee. J Neurooncol 135:629–638. https://doi.org/10.1007/s11060-017-2616-4
Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O’Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23:5034–5043. https://doi.org/10.1200/jco.2005.13.524
Omuro AMP, DeAngelis LM, Karrison T, Bovi JA, Rosenblum M, Corn BW, Correa D, Wefel JS, Aneja S, Grommes C, Schaff L, Waggoner SE, Lallana EC, Werner-Wasik M, Iwamoto F, Robinson TJ, Donnelly E, Struve T, Won M, Mehta MP (2020) 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 Clin Oncol 38:2501–2501. https://doi.org/10.1200/JCO.2020.38.15_suppl.2501
Dahiya S, Murphy ES, Chao ST, Stevens GH, Peereboom DM, Ahluwalia MS (2013) Recurrent or refractory primary central nervous lymphoma: therapeutic considerations. Expert Rev Anticancer Ther 13:1109–1119. https://doi.org/10.1586/14737140.2013.829634
Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS (2005) Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol 23:1507–1513. https://doi.org/10.1200/jco.2005.01.161
Hottinger AF, DeAngelis LM, Yahalom J, Abrey LE (2007) Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 69:1178–1182. https://doi.org/10.1212/01.wnl.0000276986.19602.c1
Khimani NB, Ng AK, Chen YH, Catalano P, Silver B, Mauch PM (2011) Salvage radiotherapy in patients with recurrent or refractory primary or secondary central nervous system lymphoma after methotrexate-based chemotherapy. Ann Oncol 22:979–984. https://doi.org/10.1093/annonc/mdq548
Soussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY (2009) CNS complications of radiotherapy and chemotherapy. Lancet 374:1639–1651. https://doi.org/10.1016/s0140-6736(09)61299-x
Correa DD, Shi W, Abrey LE, Deangelis LM, Omuro AM, Deutsch MB, Thaler HT (2012) Cognitive functions in primary CNS lymphoma after single or combined modality regimens. Neuro-oncology 14:101–108. https://doi.org/10.1093/neuonc/nor186
Abrey LE, DeAngelis LM, Yahalom J (1998) Long-term survival in primary CNS lymphoma. J Clin Oncol 16:859–863. https://doi.org/10.1200/jco.1998.16.3.859
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Conceptualization: DHL; Methodology: NK, DHL; Formal analysis and investigation: NK, DHL, SEY, SJK, WSK; Writing-original draft preparation: NK, DHL; Writing-review and editing: NK, DHL, SEY, SJK, WSK; Resources: DHL, SEY, SJK, WSK; Supervision: DHL.
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Kim, N., Lim, D.H., Yoon, S.E. et al. Role of 23.4 Gy upfront whole-brain radiation therapy following high-dose methotrexate for primary central nervous system lymphoma: a comparative analysis of whole-brain radiation therapy versus no radiation therapy. J Neurooncol 154, 207–217 (2021). https://doi.org/10.1007/s11060-021-03815-6
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DOI: https://doi.org/10.1007/s11060-021-03815-6