Radiotherapy for the treatment of primary intraocular lymphoma and orbital (ocular adnexa) lymphomas

Abstract Primary intraocular lymphoma (PIOL) is a lymphomatous proliferation seen in the eye and can be subdivided into two groups: (1) those which occur in the vitreous and /or retina and (2) those which occur in the uvea [1]. The histology is usually diffuse large B‐cell lymphoma (DLBCL) and diagnosis is made by vitrectomy, vitreal biopsy, or choroidal sampling. Vitreoretinal lymphomas are lymphomas that arise primarily in the vitreous and/or the retina and are considered as a part of the primary central nervous system lymphomas (PCNSL). Primary uveal lymphomas start as a primary disease in the uveal tract. Because brain was the most common site of relapse, some old data recommended in the past to treat as for PCNSL [2]. Modern data suggest that in case of brain relapse, salvage tratements remain effective [3]. Most patients with PIOL present a high risk of bilateral involvement, even when pathologic results have been obtained from only one eye. Ocular irradiation should include both eyes. However, when there is no suspicion of disease in the contralateral eeye, it is reasonable to treat onlym the involved eye. The volume of irradiation has to include the globe of the eye (s), optic nerves (s) to the level of the chiasm. Low dose of 30‐36 Gy is recommended [4]. Primary lymphoma of the ocular adnexa (orbital lymphoma) is a very rare tumor entity and accounts less than 1% of all non‐Hodgkin lymphomas (NHL) and 8% of all extranodal NHL [5]. Most cases of extraocular orbital lymphoma are marginal zone lymphoma (MZL) and involve the conjunctiva, lacrimal gland, eyelid, or retrobulbar soft tissues. Less common are follicular lymphoma (FL) and DLBCL. Primary radiation therapy (RT) is the curative option in patients with indolent lymphoma with high response rate and acceptable toxicity [6]. RT may be indicated to consolidate systemic therapy for DLBCL. For most cases of indolent NHL, the entire bony orbit has to be included. When the disease is limited to the conjunctiva, the irradiation has to include the entire conjunctival sac and local extensions to eyelid. A standard dose of 24 to 25 Gy in 1.5 to 2 Gy per fraction is prescribed. Since indolent lymphomas are highly radiosensitive, low dose irradiation (4 Gy in 2 fractions of 2 Gy) has been used in order to minimize the toxicity. A randomized non‐inferiority trial (FORT) compared conventional radiation scheme (24 Gy) to low dose RT (4Gy) in patients with FL. Low dose RT showed inferior results in term of local progression free survival [7]. REFERENCES Venkatesh R, Bavaharan B, Mahendradas P, Yadav NK. Primary vitreoretinal lymphoma: prevalence, impact, and management challenges. Clin Ophthalmol. 2019;13:353‐64. Akpek EK, Ahmed I, Hochberg FH, Soheilian M, Dryja TP, Jakobiec FA, et al. Intraocular‐central nervous system lymphoma: clinical features, diagnosis, and outcomes. Ophthalmology. 1999;106:1805‐10. Teckie S, Yahalom J. Primary intraocular lymphoma: treatment outcomes with ocular radiation therapy alone. Leuk Lymphoma. 2014;55:795‐801. Yahalom J, Illidge T, Specht L, Hoppe RT, Li YX, Tsang R, 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;92:11‐31. Margo CE, Mulla ZD. Malignant tumors of the orbit. Analysis of the Florida Cancer Registry. Ophthalmology. 1998;105:185‐90. Fakhrian K, Klemm S, Keller U, Bayer C, Riedl W, Molls M, et al. Radiotherapy in stage I‐III follicular non‐Hodgkin lymphoma. Retrospective analysis of a series of 50 patients. Strahlenther Onkol. 2012;188:464‐70. Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop‐Evans E, et al. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non‐inferiority trial. Lancet Oncol. 2014;15:457‐63.