For a patient with a non‑MALT orbital lymphoma recurrence presenting with gross disease, what curative radiation dose should be administered?

Radiation Dose for Non-MALT Orbital Lymphoma Recurrence with Gross Disease

For a non-MALT orbital lymphoma recurrence presenting with gross disease, deliver 36–40 Gy using involved-site radiotherapy (ISRT) if the orbit has not been previously irradiated. 1, 2

Dose Selection Based on Histology

Non-MALT orbital lymphomas are typically intermediate- or high-grade histologies (diffuse large B-cell, follicular grade 3, or transformed lymphomas) that require higher radiation doses than indolent MALT lymphomas to achieve durable local control. 1, 3

• Deliver 36–40 Gy in 1.8–2.0 Gy fractions for intermediate/high-grade orbital lymphomas. 1, 2
• The Stanford experience demonstrated that intermediate and high-grade orbital lesions required 36–40 Gy for optimal control, compared to 30–35 Gy for low-grade disease. 1
• A German series treating aggressive orbital lymphomas used a median dose of 44 Gy (range 20–48 Gy), achieving 80% local control in advanced stages. 2

Evidence Supporting Higher Doses for Non-Indolent Histologies

Patients with intermediate/high-grade orbital lymphoma have significantly worse outcomes than those with indolent disease, with 5-year cause-specific survival of only 33% versus 89% for low-grade histology. 4

• In-field failures in intermediate/high-grade lymphomas occurred evenly across the dose range, with 8 failures distributed throughout, suggesting that doses below 36 Gy are insufficient for aggressive histologies. 3
• All in-field failures in low-grade disease occurred at doses <30 Gy, but no such threshold was protective for intermediate/high-grade disease at lower doses. 3

Treatment Planning Specifications

Use ISRT technique following International Lymphoma Radiation Oncology Group (ILROG) definitions for extranodal sites. 5

• Employ photon beams (6–10 MV) to cover the entire orbit when intraorbital tissues are involved. 6
• Electrons (9–12 MeV) may be used only if disease is strictly confined to conjunctiva or eyelid, which is uncommon in recurrent gross disease. 6
• Deliver 1.8–2.0 Gy per fraction, five fractions per week, never exceeding 2 Gy per fraction. 7

Critical Organ-at-Risk Constraints

Implement lens shielding whenever anatomically feasible to prevent cataract formation. 1, 4

• Cataract risk increases markedly when lens dose exceeds 4–5 Gy; seven of 21 patients without lens shielding developed cataracts versus zero of 17 with shielding. 4, 5
• Keep total orbital dose below 36 Gy when possible to minimize risk of ischemic retinopathy, optic atrophy, corneal ulceration, and glaucoma. 7, 5
• However, for non-MALT recurrent disease with gross involvement, oncologic control takes priority; doses of 36–40 Gy are justified despite slightly elevated late toxicity risk. 2

When Radiation Is Not Feasible

If the orbit has already received maximum safe radiation dose, transition to systemic therapy rather than attempting re-irradiation. 5

• Rituximab plus chlorambucil is the preferred systemic regimen, supported by phase III evidence showing superior complete response and progression-free survival in marginal-zone lymphomas. 5
• Rituximab monotherapy, alkylating agents (cyclophosphamide, chlorambucil), or purine analogues (fludarabine, cladribine) are acceptable alternatives. 5

Common Pitfalls to Avoid

• Do not use the 24 Gy dose recommended for indolent MALT lymphomas; non-MALT histologies require 36–40 Gy for adequate control. 1, 2
• Do not use the ultra-low 4 Gy/2-fraction palliative regimen for curative-intent treatment of recurrent gross disease. 7, 5
• Do not compromise dose to avoid late effects in patients with aggressive histology and gross disease; local control is the priority for survival. 2, 3
• Doses exceeding 36 Gy increase grade 3 late complications (primarily cataract and dry eye), but this risk is acceptable for non-indolent recurrent disease. 2