Introduction

• MALT lymphoma: indolent neoplasm, 7-8% of B-cell non-Hodgkin lymphomas
• Early-stage disease has favorable prognosis
• Radiation therapy (RT) can achieve long-term disease control
• Limited prospective data on long-term outcomes and toxicities
• Study objective: determine efficacy, safety, and salvage outcomes of RT alone for localized MALT lymphoma

Methods

• Single-center, prospective trial
• Eligibility: stage I, II, or IV (due to bilateral involvement) MALT lymphoma
• Treatment: involved field RT, 24-39.6 Gy
• Primary endpoint: relapse-free survival (RFS)
• Secondary endpoints: progression-free survival (PFS), overall survival (OS), toxicity
• Preplanned subgroup analyses by site of involvement

Patient Population

• 75 patients accrued (2000-2012),
  • 73 received protocol-specified RT
• Median age: 57 years (range 25-84)
• Stage: I (84%), II (13%), IV (3%)
• Sites: gastric (47%), orbit (23%), head and neck non-orbit (18%), skin (5%), other (7%)
• 13/34 gastric MALT patients H. pylori positive at diagnosis
• Median follow-up: 9.8 years

Radiation Protocol

• Involved field RT: 24-30.6 Gy in 1.8-2 Gy per fraction
• Boost to tumors >5 cm allowed up to 39.6 Gy
• CT-based planning required (except cutaneous MALT)
• Gastric MALT: empty stomach, entire stomach treated with 2 cm margin
• Dose distribution:
  • 24-28.5 Gy (11%)
  • 30-30.6 Gy (62%)
  • 33-39.6 Gy (27%)
• All treatment plans peer-reviewed before start of RT

Primary Outcome

• All patients achieved complete response (median time: 3 months)
• 11 patients (15%) relapsed (median time to progression: 38.3 months)
• 10-year relapse-free survival: 83% (95% CI: 74%-93%)
• Median RFS: not reached
• No significant difference in RFS by disease site (p=0.17)

Primary Outcome

Secondary Outcomes

• Median PFS: 17.5 years (95% CI: 11.5 years to N/A)
• 10-year PFS: 71% (95% CI: 60%-84%)
• 10-year OS: 86% (95% CI: 77%-96%)
• No significant difference in PFS or OS by disease site
• All relapses successfully salvaged
• No disease transformation to aggressive lymphoma
• One patient (1%) developed secondary malignancy (gastric adenocarcinoma)

Secondary Outcomes

• Median PFS: 17.5 years (95% CI: 11.5 years to N/A)
• 10-year PFS: 71% (95% CI: 60%-84%)
• 10-year OS: 86% (95% CI: 77%-96%)
• No significant difference in PFS or OS by disease site
• All relapses successfully salvaged
• No disease transformation to aggressive lymphoma
• One patient (1%) developed secondary malignancy (gastric adenocarcinoma)

Toxicity

• Acute toxicity: 92% of patients, mostly grade 1-2
• Most common acute toxicities: nausea (38%), dermatitis (33%), fatigue (18%), eye symptoms (18%)
• One grade 3 acute toxicity: retinal detachment
• Late toxicity: 30% of patients, mostly grade 1-2
• Most common late toxicities: cataracts (8%), dry eye (7%), xerostomia (10%)
• One grade 3 late toxicity: severe retinopathy (same patient as acute toxicity)

Conclusions

• RT for localized MALT lymphoma provides excellent long-term disease control
• High complete response rate (100%) with durable remissions
• Low rate of relapse (15%) with successful salvage treatment
• No disease-specific deaths observed
• Acceptable toxicity profile, mostly low-grade
• Results affirm the use of RT as definitive treatment in early-stage MALT lymphoma
• Further studies on dose de-escalation may help minimize toxicity

Strengths and Limitations

• Strengths:
  - Prospective design
  - Long-term follow-up (median 9.8 years)
  - Comprehensive reporting of outcomes and toxicities
• Limitations:
  - Single-center study
  - Higher radiation doses than current standards
  - Use of involved field RT vs. current involved site RT
  - Limited use of PET staging (60% of patients)
  - Lack of data on t(11;18) translocation status

Discussion Points

1. How might the results of this study impact current practice for early-stage MALT lymphoma?
2. What are the potential benefits and risks of dose de-escalation in RT for MALT lymphoma?
3. How does the toxicity profile observed in this study compare to more modern RT techniques and doses?
4. What role does PET staging play in the management of MALT lymphoma, and how might it have affected the results of this study?
5. How should we approach the management of relapsed MALT lymphoma after initial RT, given the excellent salvage outcomes observed in this study?