Modern radiation therapy for extranodal lymphomas:field and dose guidelines from international lymphomaradiation oncology group
Joachim Yahalom,MD1,Tim Illidge,MD,PhD2,Lena Specht,MD,PhD3,Richard T.Hoppe,MD4,Ye-Xiong Li,MD5,Richard Tsang,MD6,and Andrew Wirth,MD7,on behalf of International Lymphoma Radiation Oncology Group
1Department of Radiation Oncology,Memorial Sloan-Kettering Cancer Center,New York,New York;2Institute of Cancer Sciences,University of Manchester,Manchester Academic Health Sciences Centre,The Christie National Health Service Foundation Trust,Manchester,United Kingdom;3Department of Oncology and Hematology,Rigshospitalet,University of Copenhagen,Copenhagen,Denmark;4Department of Radiation Oncology,Stanford University,Palo Alto,California;5Department of Radiation Oncology,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,People’s Republic of China;6Department of Radiation Oncology,Princess Margaret Hospital,University of Toronto,Toronto,Ontario,Canada;and 7Division of Radiation Oncology,Peter MacCallum Cancer Institute,St. Andrews Place,East Melbourne,Australia Yang Zhuanbo,Liu Xin,Qi Shunan,Li Yexiong,Translation Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100005,China (Yang ZB);Department of Radiation Oncology,National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100021,China (Liu X,Qi SN,Li YX)
Abstract：Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL).Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL),consolidation after systemic therapy,salvage treatment,or palliation. The wide range of presentations of ENL,involving any organ in the body and the spectrum of histological sub-types,poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL.This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL,and to address the technical challenges of simulation,volume definition and treatment planning for the most frequently involved organs. Specifically,detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL.We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU),as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype,anatomy,the treatment intent,and other treatment modalities that may be have been used before RT.
. Modern radiation therapy for extranodal lymphomas:field and dose guidelines from international lymphomaradiation oncology group[J]. Chinese Journal of Radiation Oncology, 2017, 26(9): 971-984.
[1] Newton R,Ferlay J,Beral V,et al. The epidemiology of non-hodgkin’s lymphoma:comparison of nodal and extra-nodal sites[J].Int J Cancer,1997,72(6):923-930. [2] Illidge T,Specht L,Yahalom J,et al. Modern radiation therapy for nodal non-Hodgkin lymphoma-target definition and dose guidelines from the international lymphoma radiation oncology group[J].Int J Radiat Oncol Biol Phys,2014,89(1):49-58.DOI:10.1016/j.ijrobp.2014.01.006. [3] Yahalom J.Radiotherapy of follicular lymphoma:Updated role and new rules[J].Curr Treat Options Oncol,2014,15(2):262-8.DOI:10.1007/s11864-014-0286-4. [4] Lowry L,Smith P,Qian W,et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma:A randomised phase Ⅲ trial[J].Radiother Oncol,2011,100(1):86-92.DOI:10.1016/j.radonc.2011.05.013. [5] Hoskin PJ,Kirkwood AA,Popova B,et al.4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT):A randomised phase 3 non-inferiority trial[J].Lancet Oncol, 2014,15(4):457-463.DOI:10.1016/S1470-2045(14)70036-1.Epub 2014 Feb 24. [6] Zelenetz AD,Gordon LI,Wierda WG,et al. Non-Hodgkin’s lymphomas,version 4.2014[J].J Natl Compr Canc Netw, 2014,12:1282-1303. [7] Hoppe BS,Moskowitz CH,Filippa DA,et al. Involved-field radiotherapy before high-dose therapy and autologous stem-cell rescue in diffuse large-cell lymphoma:Long-term disease control and toxicity[J].J Clin Oncol,2008,10;26(11):1858-1864.DOI:10.1200/JCO.2007.15.4773. [8] Yahalom J.Management of relapsed and refractory Hodgkin’s disease[J].Semin Radiat Oncol,1996,6(3):210-224. [9] Specht L,Yahalom J,Illidge T,et al. Modern radiation therapy for Hodgkin lymphoma:Field and dose guidelines from the International Lymphoma Radiation Oncology Group (ILROG)[J].Int J Radiat Oncol Biol Phys,2014,15;89(4):854-862.DOI:10.1016/j.ijrobp.2013.05.005. [10] Gregoire V,Mackie TR.State of the art on dose prescription,reporting and recording in intensity-modulated radiation therapy (ICRU report no.83)[J].Cancer Radiother, 2011,15(6-7):555-559.DOI:10.1016/j.canrad.2011.04.003. [11] Milgrom SA,Yahalom J.The role of radiation therapy in the management of primary central nervous system lymphoma[J].Leuk Lymphoma,2015,56(5):1197-204.DOI:10.3109/10428194.2014.961014.Epub 2014 Oct 21. [12] Omuro AM,Ben-Porat LS,Panageas KS,et al. Delayed neurotoxicity in primary central nervous system lymphoma[J].Arch Neurol, 2005,62(10):1595-1600. [13] 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. [14] Shah GD,Yahalom J,Correa DD,et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma[J].J Clin Oncol,2007,25(30):4730-4735. [15] Correa DD,Rocco-Donovan M,DeAngelis LM,et al. Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy[J].J Neurooncol,2009,91(3):315-321.DOI:10.1007/s11060-008-9716-0. [16] 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. [17] Hottinger AF,DeAngelis LM,Yahalom J,et al. Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma[J].Neurology,2007,11;69(11):1178-1182. [18] Nguyen PL,Chakravarti A,Finkelstein DM,et al. Results of wholebrain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma[J].J Clin Oncol,2005,23(7):1507-1513. [19] Lai R,Rosenblum MK,DeAngelis LM.Primary CNS lymphoma:A whole-brain disease?[J] Neurology,2002,59(10):1557-1562. [20] Ferreri AJ.How I treat primary CNS lymphoma[J].Blood,2011,118(3):510-522.DOI:10.1182/blood-2011-03-321349. [21] 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. [22] Akpek EK,Ahmed I,Hochberg FH,et al. Intraocular-central nervous system lymphoma:Clinical features,diagnosis,and outcomes[J].Ophthalmology,1999,106(9):1805-1810. [23] Grimm SA,McCannel CA,Omuro AM,et al. Primary CNS lymphoma with intraocular involvement:International PCNSL collaborative group report[J].Neurology,2008,71(17):1355-1360.DOI:10.1212/01.wnl.0000327672.04729.8c. [24] Teckie S,Yahalom J.Primary intraocular lymphoma:treatment outcomes with ocular radiation therapy alone[J].Leuk Lymphoma,2014,55(4):795-801.DOI:10.3109/10428194.2013.819576. [25] Smith JR,Rosenbaum JT,Wilson DJ,et al. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement[J].Ophthalmology,2002,109(9):1709-1716. [26] Puri DR,Tereffe W,Yahalom J.Low-dose and limited-volume radiotherapy alone for primary dural marginal zone lymphoma:Treatment approach and review of published data[J].Int J Radiat Oncol Biol Phys,2008,71(5):1425-1435.DOI:10.1016/j.ijrobp.2007.12.007. [27] Stefanovic A,Lossos IS.Extranodal marginal zone lymphoma of the ocular adnexa[J].Blood,2009,114(3):501-510.DOI:10.1182/blood-2008-12-195453. [28] Fung CY,Tarbell NJ,Lucarelli MJ,et al. Ocular adnexal lymphoma:Clinical behavior of distinct World Health Organization classification subtypes[J].Int J Radiat Oncol Biol Phys,2003,57(5):1382-1391. [29] Goda JS,Gospodarowicz M,Pintilie M,et al. Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy[J].Cancer,2010,116(16):3815-3824.DOI:10.1002/cncr.25226. [30] Pfeffer MR,Rabin T,Tsvang L,et al. Orbital lymphoma:Is it necessary to treat the entire orbit?[J] Int J Radiat Oncol Biol Phys,2004,60(2):527-530. [31] Jeganathan VS,Wirth A,MacManus MP.Ocular risks from orbital and periorbital radiation therapy:A critical review[J].Int J Radiat Oncol Biol Phys,2011 Mar 1;79(3):650-9.DOI:10.1016/j.ijrobp.2010.09.056. [32] Tran KH,Campbell BA,Fua T,et al. Efficacy of low dose radiotherapy for primary orbital marginal zone lymphoma[J].Leuk Lymphoma,2013 Mar;54(3):491-6.DOI:10.3109/10428194.2012.717279.Epub 2012 Sep 28. [33] Kaushik M,Pulido JS,Schild SE,et al. Risk of radiation retinopathy in patients with orbital and ocular lymphoma[J].Int J Radiat Oncol Biol Phys,2012 Dec 1;84(5):1145-50.DOI:10.1016/j.ijrobp.2011.12.097.Epub 2012 May 15. [34] Suh CO,Shim SJ,Lee SW,et al. Orbital marginal zone B-cell lymphoma of MALT:Radiotherapy results and clinical behavior[J].Int J Radiat Oncol Biol Phys,2006,65(1):228-233. [35] Frierson HFJr., Mills SE,Innes DJJr. Non-Hodgkin’s lymphomas of the sinonasal region:Histologic subtypes and their clinicopathologic features[J].Am J Clin Pathol,1984,81(6):721-727. [36] Logsdon MD,Ha CS,Kavadi VS,et al. Lymphoma of the nasal cavity and paranasal sinuses:Improved outcome and altered prognostic factors with combined modality therapy[J].Cancer,1997,80(3):477-488. [37] Murawski N,Held G,Ziepert M,et al. The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas[J].Blood,2014,124(5):720-8.DOI:10.1182/blood-2013-10-535021. [38] Tran LM,Mark R,Fu YS,et al. Primary non-Hodgkin’s lymphomas of the paranasal sinuses and nasal cavity:A report of 18 cases with stage Ⅰ e disease[J].Am J Clin Oncol,1992,5(3):222-225. [39] Ezzat AA,Ibrahim EM,El Weshi AN,et al. Localized non-Hodgkin’s lymphoma of Waldeyer’s ring:Clinical features,management,and prognosis of 130 adult patients[J].Head Neck,2001,23(7):547-558. [40] Gurkaynak M,Cengiz M,Akyurek S,et al. Waldeyer’s ring lymphomas:Treatment results and prognostic factors[J].Am J Clin Oncol,2003,26(5):437-440. [41] Qi SN,Li YX,Wang H,et al. Diffuse large B-cell lymphoma:Clinical characterization and prognosis of Waldeyer ring versus lymph node presentation[J].Cancer,2009,115(21):4980-4989.DOI:10.1002/cncr.24557. [42] Chang DT,Mendenhall NP,Lynch JW,et al. Long-term outcomes for stage Ⅰ—Ⅱ aggressive non-Hodgkin lymphoma of Waldeyer’s ring[J].Am J Clin Oncol,2009,32(3):233-237.DOI:10.1097/COC.0b013e318187 ddbb. [43] Laskar S,Mohindra P,Gupta S,et al. Non-Hodgkin lymphoma of the Waldeyer’s ring:Clinicopathologic and therapeutic issues[J].Leuk Lymphoma,2008,49(12):2263-2271.DOI:10.1080/10428190802493686. [44] Mohammadianpanah M,Omidvai S,Mosalei A,et al. Treatment results of tonsillar lymphoma:A 10-year experience[J].Ann Hematol,2005,84(4):223-226. [45] Anacak Y,Miller RC,Constantinou N,et al. Primary mucosaassociated lymphoid tissue lymphoma of the salivary glands:A multicenter rare cancer network study[J].Int J Radiat Oncol Biol Phys,2012,82(1):315-320.DOI:10.1016/j.ijrobp.2010.09.046. [46] Ambrosetti A,Zanotti R,Pattaro C,et al. Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection[J].Br J Haematol,2004,126(1):43-49. [47] Tsang RW,Gospodarowicz MK,Pintilie M,et al. Localized mucosaassociated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome[J].J Clin Oncol,2003,21(22):4157-4164. [48] Alzouebi M,Goepel JR,Horsman JM,et al. Primary thyroid lymphoma:The 40 year experience of a UK lymphoma treatment centre[J].Int J Oncol,2012,40(6):2075-2080.DOI:10.3892/ijo.2012.1387. [49] Costa LJ,Xavier AC.Features and outcomes of diffuse large B-cell lymphoma of the thyroid in a large contemporary cohort[J].Leuk Lymphoma,2014,55(2):283-287.DOI:10.3109/10428194.2013.802317. [50] Walsh S,Lowery AJ,Evoy D,et al. Thyroid lymphoma:Recent advances in diagnosis and optimal management strategies[J].Oncologist,2013,18(9):994-1003.DOI:10.1634/theoncologist.2013-0036. [51] Au WY,Weisenburger DD,Intragumtornchai T,et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma:A study of 136 cases from the international peripheral T-cell lymphoma project[J].Blood,2009,113(17):3931-3937.DOI:10.1182/blood-2008-10-185256. [52] Li YX,Liu QF,Fang H,et al. Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma[J].Clin Cancer Res,2009,15(8):2905-2912.DOI:10.1158/1078-0432.CCR-08-2914. [53] Kim SJ,Kim K,Kim BS,et al. Phase Ⅱ trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed,stage Ⅰ e to Ⅱ e,nasal,extranodal NK/T-cell lymphoma:Consortium for improving survival of lymphoma study[J].J Clin Oncol,2009,27(35):6027-6032.DOI:10.1200/JCO.2009.23.8592. [54] Wang ZY,Li YX,Wang WH,et al. Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents[J].Blood,2009,114(23):4771-4776.DOI:10.1182/blood-2009-07-235853. [55] Li YX,Yao B,Jin J,et al. Radiotherapy as primary treatment for stage ie and iie nasal natural killer/t-cell lymphoma[J].J Clin Oncol,2006,24(1):181-189. [56] Abrey LE,Yahalom J,DeAngelis LM.Treatment for primary CNS lymphoma:The next step[J].J Clin Oncol,2000,18(17):3144-3150. [57] Wang H,Li YX,Wang WH,et al. Mild toxicity and favorable prognosis of high-dose and extended involved-field intensity-modulated radiotherapy for patients with early-stage nasal NK/T-cell lymphoma[J].Int J Radiat Oncol Biol Phys,2012,82(3):1115-1121.DOI:10.1016/j.ijrobp.2010.8.040. [58] Li YX,Wang H,Jin J,et al. Radiotherapy alone with curative intent in patients with stage Ⅰ extranodal nasal-type NK/T-cell lymphoma[J].Int J Radiat Oncol Biol Phys,2012,82(5):1809-1815.DOI:10.1016/j.ijrobp.2010.10.040. [59] Yamaguchi M,Kwong YL,Kim WS,et al. Phase Ⅱ study of SMILE chemotherapy for newly diagnosed stage ⅠV,relapsed,or refractory extranodal natural killer (NK)/T-cell lymphoma,nasal type:The NKcell tumor study group study[J].J Clin Oncol,2011,29(33):4410-6.DOI:10.1200/JCO.2011.35.6287.Epub 2011 Oct 11. [60] Wang L,Xia ZJ,Lu Y,et al. Prophylactic cervical lymph node irradiation provides no benefit for patients of stage Ⅰ e extranodal natural killer/T cell lymphoma,nasal type[J].Med Oncol,2015,32(1):320.DOI:10.1007/s12032-014-0320-1. [61] Tomita N,Kodaira T,Tachibana H,et al. A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma[J].Br J Radiol,2009,82(981):756-763.DOI:10.1259/bjr/83758373. [62] Bi XW,Li YX,Fang H,et al. High-dose and extended-field intensity modulated radiation therapy for early-stage NK/T-cell lymphoma of Waldeyer’s ring:Dosimetric analysis and clinical outcome[J].Int J Radiat Oncol Biol Phys,2013,87(5):1086-1093.DOI:10.1016/j.ijrobp.2013.08.040. [63] Li YX,Fang H,Liu QF,et al. Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring[J].Blood,2008,112(8):3057-3064.DOI:10.1182/blood-2008-05-160176. [64] Caon J,Wai ES,Hart J,et al. Treatment and outcomes of primary breast lymphoma[J].Clin Breast Cancer,2012,12(6):412-419.DOI:10.1016/j.clbc.2012.07.006. [65] Martinelli G,Ryan G,Seymour JF,et al. Primary follicular and marginal-zone lymphoma of the breast:Clinical features,prognostic factors and outcome:A study by the international extranodal lymphoma study group[J].Ann Oncol,2009,20(12):1993-1999.DOI:10.1093/annonc/mdp238. [66] Ryan G,Martinelli G,Kuper-Hommel M,et al. Primary diffuse large B-cell lymphoma of the breast:Prognostic factors and outcomes of a study by the international extranodal lymphoma study group[J].Ann Oncol,2008,19(2):233-241. [67] Ahmed S,Siddiqui AK,Rai KR.Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma[J].Cancer Invest,2002,20(7-8):1059-1068. [68] Yahalom J.MALT lymphomas:a radiation oncology viewpoint[J].Ann Hematol,2001,80 Suppl 3:B100-5. [69] Wirth A,Gospodarowicz M,Aleman BM,et al. Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy:A retrospective,multi-centre,international extranodal lymphoma study group study[J].Ann Oncol,2013,24(5):1344-1351.DOI:10.1093/annonc/mds623. [70] Della Biancia C,Hunt M,Furhang E,et al. Radiation treatment planning techniques for lymphoma of the stomach[J].Int J Radiat Oncol Biol Phys,2005,62(3):745-751. [71] Kiess AP,Yahalom J.Primary follicular lymphoma of the gastrointestinal tract:Effect of stage,symptoms and treatment choice on outcome[J].Leuk Lymphoma,2013,54(1):177-180.DOI:10.3109/10428194.2012.698390. [72] Ahmad SS,Idris SF,Follows GA,et al. Primary testicular lymphoma[J].Clin Oncol,2012,24(5):358-365.DOI:10.1016/j.clon.2012.02.005. [73] Cheah CY,Wirth A,Seymour JF.Primary testicular lymphoma[J].Blood,2014,123(4):486-493.DOI:10.1182/blood-2013-10-530659. [74] Mikhaeel NG.Primary bone lymphoma[J].Clin Oncol,2012,24(5):366-370.DOI:10.1016/j.clon.2012.02.006.
2017, Vol. 26 
