What is the recommended definitive external‑beam radiotherapy regimen (dose, fractionation, and technique) for a patient with stage I‑E primary intra‑orbital marginal zone (MALT) lymphoma confined to the orbit?

Radiation Therapy for Stage I-E Intraorbital MALT Lymphoma

For stage I-E primary intraorbital MALT lymphoma, the standard definitive treatment is external-beam radiotherapy at 24-30 Gy delivered in 1.5-2 Gy fractions over 3-4 weeks using involved-site radiotherapy technique with lens shielding whenever anatomically feasible. 1

Recommended Radiation Dose and Fractionation

• Standard dose: 24-30 Gy is the established regimen for localized extranodal marginal zone lymphomas, including orbital MALT, with excellent disease control 1
• The UK phase III trial demonstrated that 24 Gy achieves equivalent long-term local tumor control compared to higher doses in indolent lymphomas including MALT 1
• Fractionation should be 1.5-2 Gy per fraction delivered over 3-4 weeks 1, 2
• Most contemporary series use 25 Gy in 10 fractions as the practical standard, achieving 98% local control at 5 years 3

Radiation Technique

• Megavoltage photon beams (6 MV) are preferred for retrobulbar/deep orbital lesions requiring complex treatment planning 2, 3
• Electron beams (9-20 MeV) with lens shielding are optimal for conjunctival and anterior lesions, used in 77% of conjunctival cases 2, 3
• Involved-site radiotherapy (ISRT) volumes should follow International Lymphoma Radiation Oncology Group (ILROG) guidelines for extranodal lymphomas 1
• Lens shielding with suspended eye bar is mandatory whenever anatomically feasible, as it significantly reduces cataract risk (25% vs higher rates without shielding) and improves 5-year progression-free survival (90.1% vs 82.1%) 4, 5, 2

Expected Outcomes

• Complete response rates: 88-99% with standard-dose radiotherapy 4, 2, 3
• Local control: 97-100% at 5-10 years, making this one of the most radiocurable malignancies 4, 2, 3, 6
• Cause-specific survival: 96-98% at 7-10 years 4, 6
• Relapse patterns: When relapse occurs (22-25% of patients), it is predominantly distant (68%) or contralateral orbit (23%), with local recurrence rare (3.5-9%) 4, 5, 6

Alternative Low-Dose Approach (Context-Specific)

• Ultra-low dose 4 Gy in 2 fractions may be considered specifically for elderly patients, those requiring palliative treatment, or when treating critical anatomical sites where standard doses pose unacceptable toxicity risk 1
• This approach achieves 96% response rates and 96% local control at 2 years in retrospective U.S. data, with substantially reduced cataract risk 1
• However, 24 Gy remains the standard recommended dose for definitive treatment in fit patients, with low-dose reserved for specific circumstances 1

Radiation Toxicity Profile

Common Late Effects:

• Cataracts are the most frequent complication, occurring in 13-25% at 7 years, predominantly Grade 3 requiring surgical intervention 4, 5, 3
• Cataract risk is dose-dependent: significantly increased with doses >30 Gy, and substantially reduced with lens shielding and doses ≤30 Gy 1, 4, 5
• Dry eye syndrome occurs in 16-27% of patients (mostly Grade 1-2), manageable with artificial tears 4, 5, 3

Rare Serious Complications (doses >36 Gy):

• Ischemic retinopathy, optic atrophy, corneal ulceration, and glaucoma are uncommon with doses below 36 Gy 1
• Clinically significant retinal damage occurred in 2 patients receiving ≥40 Gy in one series 2

Management of Toxicities:

• Most late effects are successfully managed: 75% of patients with complications achieved complete resolution, with only 10% having persistent sequelae 4
• Acute toxicities (dry eye) typically subside gradually over months with conservative management 5
• Surgical intervention for cataracts is successful when required 4

Critical Clinical Pitfalls to Avoid

• Do not exceed 30-30.6 Gy for definitive treatment, as higher doses increase toxicity without improving local control 2, 6
• Do not omit lens shielding when anatomically feasible—this is the single most important factor in reducing cataract formation and other late sequelae 4, 5
• Do not use improper lens shielding technique, as this was associated with all 3 local recurrences in one series 6
• Do not perform extensive staging workup or intensive surveillance for distant disease in truly localized orbital MALT, as it rarely presents with or develops extraorbital involvement (only 4% in one series) 6

Practical Treatment Algorithm

1. Confirm stage I-E disease with appropriate staging (CT chest/abdomen/pelvis, bone marrow biopsy if systemic symptoms present)
2. Determine anatomical extent: conjunctival vs. lacrimal gland vs. retrobulbar soft tissue
3. Select radiation modality:
   • Electrons with lens shielding for conjunctival/anterior lesions
   • Megavoltage photons for deep orbital/retrobulbar disease
4. Deliver 24-30 Gy (typically 25 Gy in 10 fractions) using ISRT technique
5. Implement lens shielding whenever anatomically possible
6. Monitor for response at 3-6 months post-treatment (expect 99% complete response)
7. Long-term surveillance focuses on contralateral orbit and distant sites, not intensive local imaging

This approach achieves cure in the vast majority of patients while minimizing vision-threatening complications through appropriate dose selection and meticulous technique. 1, 4, 2, 3, 6