Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis.
indolent non-hodgkin lymphoma
orbital lymphoma
radiotherapy
recurrence analysis
toxicity
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
revised:
01
03
2022
received:
16
11
2021
accepted:
07
03
2022
pubmed:
12
3
2022
medline:
15
6
2022
entrez:
11
3
2022
Statut:
ppublish
Résumé
To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma. We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. At diagnosis, the median age was 63.5 years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6-48.6 Gy) delivered in 1.8-2 Gy single fractions. At a median follow-up of 83 months (range: 7-258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21-30Subventions
Organisme : LUDWIG-MAXIMILIANS-UNIVERSITAET MUNCHEN
Organisme : Projekt DEAL
Informations de copyright
© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
Références
Coupland SE, White VA, Rootman J, Damato B, Finger PT. A TNM-based clinical staging system of ocular adnexal lymphomas. Arch Pathol Lab Med. 2009;133(8):1262-1267. 10.1043/1543-2165-133.8.1262
Sjö LD. Ophthalmic lymphoma: epidemiology and pathogenesis. Acta Ophthalmol. 2009;87(thesis1):1-20. 10.1111/j.1755-3768.2008.01478.x
Fitzpatrick PJ, Macko S. Lymphoreticular tumors of the orbit. Int J Radiat Oncol Biol Phys. 1984;10(3):333-340. http://www.ncbi.nlm.nih.gov/pubmed/6368493. Accessed August 5, 2018.
Demirci H, Shields CL, Karatza EC, Shields JA. Orbital lymphoproliferative tumors: analysis of clinical features and systemic involvement in 160 cases. Ophthalmology. 2008;115(9):1626-1631. 10.1016/j.ophtha.2008.02.004
Ferreri AJM, Blay J-Y, Reni M, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas. Ann Oncol. 2002;13(4):531-538. 10.1093/annonc/mdf080
Cheah CY, Milgrom S, Chihara D, et al. Intensive chemoimmunotherapy and bilateral globe irradiation as initial therapy for primary intraocular lymphoma. Neuro Oncol. 2016;18(4):575-581. 10.1093/neuonc/nov253
Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol. 2019;64(1):45-66. 10.1016/j.survophthal.2018.08.002
Goda JS, Le LW, Lapperriere NJ, et al. Localized orbital mucosa-associated lymphoma tissue lymphoma managed with primary radiation therapy: efficacy and toxicity. Int J Radiat Oncol Biol Phys. 2011;81(4):659-666. 10.1016/j.ijrobp.2011.03.050
Stafford SL, Kozelsky TF, Garrity JA, et al. Orbital lymphoma: radiotherapy outcome and complications. Radiother Oncol. 2001;59(2):139-144. 10.1016/S0167-8140(00)00328-5
Minehan KJ, Martenson JA, Garrity JA, et al. Local control and complications after radiation therapy for primary orbital lymphoma: a case for low-dose treatment. Int J Radiat Oncol Biol Phys. 1991;20(4):791-796. 10.1016/0360-3016(91)90025-Y
Bischof M, Karagiozidis M, Krempien R, et al. Radiotherapy for orbital lymphoma: outcome and late effects. Strahlentherapie Und Onkol. 2007;183(1):17-22. 10.1007/s00066-007-1627-z
Fasola CE, Jones JC, Huang DD, Le Q-TT, Hoppe RT, Donaldson SS. Low-dose radiation therapy (2 Gy ?? 2) in the treatment of orbital lymphoma. Int J Radiat Oncol Biol Phys. 2013;86(5):930-935. 10.1016/j.ijrobp.2013.04.035
Pinnix CC, Dabaja BS, Milgrom SA, et al. Ultra-low-dose radiotherapy for definitive management of ocular adnexal B-cell lymphoma. Head Neck. 2017;39(6):1095-1100. 10.1002/hed.24717
König L, Stade R, Rieber J, Debus J, Herfarth K. Radiotherapy of indolent orbital lymphomas. Strahlentherapie Und Onkol. 2016;192(6):414-421. 10.1007/s00066-016-0962-3
Bolek TW, Moyses HM, Marcus RB, et al. Radiotherapy in the management of orbital lymphoma. Int J Radiat Oncol. 1999;44(1):31-36. 10.1016/S0360-3016(98)00535-5
Lowry L, Smith P, Qian W, et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011;100(1):86-92. 10.1016/J.RADONC.2011.05.013
Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI sponsored international working group. J Clin Oncol. 1999;17(4):1244-1253. 10.1200/JCO.1999.17.4.1244
Rasmussen PK, Coupland SE, Finger PT, et al. Ocular adnexal follicular lymphoma. JAMA Ophthalmol. 2014;132(7):851. 10.1001/jamaophthalmol.2014.376
Parikh RR, Moskowitz BK, Maher E, et al. Long-term outcomes and patterns of failure in orbital lymphoma treated with primary radiotherapy. Leuk Lymphoma. 2017;2014(8194):1-16. 10.3109/10428194.2014.979415
König L, Stade R, Rieber J, Debus J, Herfarth K. Radiotherapy of indolent orbital lymphomas : Two radiation concepts. Strahlenther Onkol. 2016;192(6):414-421. 10.1007/s00066-016-0962-3
Zhou P, Ng AK, Silver B, Li S, Hua L, Mauch PM. Radiation therapy for orbital lymphoma. Int J Radiat Oncol Biol Phys. 2005;63(3):866-871. 10.1016/j.ijrobp.2005.03.005
Yahalom J, Illidge T, Specht L, et al. Modern radiation therapy for extranodal lymphomas: field and dose guidelines from the international lymphoma radiation oncology group. Int J Radiat Oncol Biol Phys. 2015;92(1):11-31. 10.1016/J.IJROBP.2015.01.009
Wirth A, Mikhaeel NG, Aleman BMP, et al. Involved site radiation therapy in adult lymphomas: an overview of international lymphoma radiation oncology group guidelines. Int J Radiat Oncol Biol Phys. 2020;107(5):909-933. 10.1016/J.IJROBP.2020.03.019
NCCN Guidelines Version 5.2021 B-Cell Lymphomas. Published online 2021. https://www.nccn.org/home/member. Accessed February 24, 2022.
De Cicco L, Cella L, Liuzzi R, et al. Radiation therapy in primary orbital lymphoma: a single institution retrospective analysis. Radiat Oncol. 2009;4:60. 10.1186/1748-717X-4-60
Martinet S, Ozsahin M, Belkacémi Y, et al. Outcome and prognostic factors in orbital lymphoma: a rare cancer network study on 90 consecutive patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55(4):892-898. http://www.ncbi.nlm.nih.gov/pubmed/12605966. Accessed August 5, 2018.
Son SH, Choi BO, Kim GW, et al. Primary radiation therapy in patients with localized orbital marginal zone B-Cell lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma). Int J Radiat Oncol Biol Phys. 2010;77(1):86-91. 10.1016/j.ijrobp.2009.04.018
Olsen TG, Holm F, Mikkelsen LH, et al. Orbital lymphoma-an international multicenter retrospective study. Am J Ophthalmol. 2019;199:44-57. 10.1016/J.AJO.2018.11.002
Bessell EM, Henk JM, Whitelocke RAF, Wright JE. Ocular morbidity after radiotherapy of orbital and conjunctival lymphoma. Eye. 1987;1(1):90-96. 10.1038/eye.1987.14
Nuzzi R, Trossarello M, Bartoncini S, et al. Ocular complications after radiation therapy: an observational study. Clin Ophthalmol. 2020;14:3153-3166. 10.2147/OPTH.S263291
Niwa M, Ishikura S, Tatekawa K, et al. Radiotherapy alone for stage IE ocular adnexal mucosa-associated lymphoid tissue lymphomas: long-term results. Radiat Oncol. 2020;15(1).10.1186/S13014-020-1477-8
Tran KH, Campbell BA, Fua T, et al. Efficacy of low dose radiotherapy for primary orbital marginal zone lymphoma. Leuk Lymphoma. 2013;54(3):491-496. 10.3109/10428194.2012.717279
Baron J, Wright CM, Lee DY, et al. Low-dose radiotherapy versus moderate-dose radiotherapy for the treatment of indolent orbital adnexal lymphomas. Front Oncol. 2021;11:2662. 10.3389/FONC.2021.716002/BIBTEX
Cerrato M, Orlandi E, Vella A, et al. Efficacy of low-dose radiotherapy (2 Gy ×2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas. Br J Radiol. 2021;94(1123):20210012. 10.1259/BJR.20210012/ASSET/IMAGES/LARGE/BJR.20210012.G004.JPEG
Chelius M, Chau K, Yang J, Hajj C, Imber B, Yahalom J. Low grade, indolent lymphomas of the head and neck: comparative toxicity of standard versus very low dose radiation therapy. Hematol Oncol. 2021;39(3):304-312. 10.1002/HON.2865
Rehn S, Elsayad K, Oertel M, et al. Radiotherapy dose and volume de-escalation in ocular adnexal lymphoma. Anticancer Res. 2020;40(7):4041-4046. 10.21873/ANTICANRES.14400
Haas RLM, Poortmans P, de Jong D, et al. High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol. 2003;21(13):2474-2480. 10.1200/JCO.2003.09.542
Aviles A, Cleto S. Low-dose radiotherapy (2×2 g) versus low doses and rituximab in the treatment of marginal zone b-cell lymphoma previously untreated. Leuk Res. 2020;98:106443. 10.1016/J.LEUKRES.2020.106443
Hindsø TG, Esmaeli B, Holm F, et al. International multicentre retrospective cohort study of ocular adnexal marginal zone B-cell lymphoma. Br J Ophthalmol. 2020;104(3):357-362. 10.1136/BJOPHTHALMOL-2019-314008
Hoskin P, Popova B, Schofield O, et al. 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021;22(3):332-340. 10.1016/S1470-2045(20)30686-0