Is re‑irradiation appropriate for a ~60‑year‑old patient with isolated recurrent orbital marginal‑zone B‑cell lymphoma after prior curative radiotherapy, and what dose/fractionation and organ‑at‑risk constraints are recommended?

Re-irradiation for Recurrent Orbital Marginal-Zone B-Cell Lymphoma

Re-irradiation is appropriate and highly effective for isolated recurrent orbital marginal-zone lymphoma in a 60-year-old patient who previously received curative radiotherapy, provided organ-at-risk dose constraints can be respected. 1

Decision Framework: Prior Radiation Status Determines Feasibility

The critical first step is reconstructing the previous radiation dose distribution to determine whether safe re-irradiation is possible. 2, 3

Re-irradiation should proceed only when:

• High-dose radiation can be delivered without exceeding cumulative organ-at-risk constraints 2
• Adequate target volume coverage is achievable 2
• If these conditions cannot be met, systemic therapy becomes the preferred approach 1

Recommended Dose and Fractionation for Re-irradiation

Deliver 24 Gy in 12 fractions (2 Gy per fraction) using involved-site radiotherapy (ISRT). 1 This regimen is the evidence-based standard established by UK phase III trial data showing no compromise in long-term local control for indolent lymphomas including marginal-zone (MALT) histology. 1

Expected outcomes with this regimen:

• Response rate ≈ 96% 1
• 2-year local control ≈ 96% 1

Alternative low-dose option: 4 Gy in 2 fractions may be considered for elderly patients or when minimizing toxicity is paramount, yielding comparable response rates (≈ 96%) and 2-year local control while markedly reducing cataract risk. 1 If this low-dose approach fails, escalation to the standard 24 Gy schedule remains permissible. 1

Critical Organ-at-Risk Constraints

Lens dose constraints:

• Cataract formation and dry-eye symptoms increase markedly when lens dose exceeds 4–5 Gy 1
• Use lens shielding whenever technically feasible 4
• Studies show 0% cataract development with lens shielding versus 33% (7/21 patients) without shielding 4

Other orbital structures:

• Keep total cumulative orbital dose below 36 Gy to minimize risk of ischemic retinopathy, optic atrophy, corneal ulceration, and glaucoma 1
• These complications are uncommon when this threshold is respected 1

Reconstruction of prior dose distribution:

• Radiation plans must be based on accurate reconstruction of the previous RT dose distribution 3
• The degree of recovery from initial radiation is difficult to estimate and varies by organ 3
• Do not assume complete tissue recovery from initial radiation 3

Target Volume Delineation

Follow International Lymphoma Radiation Oncology Group (ILROG) definitions for extranodal sites when defining ISRT target volumes. 1 Partial orbit irradiation is appropriate and achieves excellent outcomes for localized orbital lymphoma, with 5-year local failure rates of only 5.3% and overall survival of 100%. 5

When Re-irradiation Is Not Feasible: Systemic Therapy Options

If maximum safe orbital dose has already been reached, transition to systemic therapy; re-irradiation is contraindicated. 1

First-line systemic regimen:

• Rituximab + chlorambucil is the preferred combination, supported by phase III randomized trial data demonstrating superior complete response, event-free survival, and progression-free survival compared with either agent alone 1
• This regimen is well-tolerated and specifically effective in marginal-zone (MALT) lymphomas 1

Alternative systemic options:

• Rituximab monotherapy (acceptable but lower efficacy than combination) 1
• Alkylating agents (cyclophosphamide, chlorambucil) 1
• Purine nucleoside analogues (fludarabine, cladribine) 1
• Antibiotic therapy may be considered when immediate sight-saving treatment is not required, with reported response rates reaching ~65% with durable remissions 1

Common Pitfalls to Avoid

Do not proceed with re-irradiation without:

• Accurate reconstruction of previous dose distribution 3
• Verification that cumulative organ-at-risk constraints can be respected 2
• Consideration of the time interval between treatments, which is a key factor for limiting toxicity 3

Do not assume:

• Complete tissue recovery from initial radiation has occurred 3
• That higher doses improve outcomes—the 24 Gy/12-fraction schedule provides equivalent control to higher doses with less toxicity 1

Clinical Outcomes and Long-term Follow-up

Radiation therapy achieves excellent local control in orbital lymphoma, with actuarial local recurrence-free survival of 84% and overall response rates of 97.7% with conventional doses. 6, 7 Long-term complications are rare, dose-dependent, and primarily related to cumulative orbital dose. 1 Close follow-up is essential, as low-dose radiotherapy preserves the option for subsequent re-irradiation with conventional doses if needed. 7