This trial studies how well ultra low-dose radiation therapy works in treating patients with stage I-IV stomach mucosa-associated lymphoid tissue (MALT) lymphoma. Ultra low-dose radiation therapy may be able to kill tumor cells and shrink tumors while having fewer side effects in patients with MALT lymphoma.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of ultra-low dose 4 Gy gastric radiation, measured as complete gastric response at one year after 4 Gy treatment in patients with marginal zone lymphoma involving the stomach (mucosa-associated lymphoid tissue [MALT]).

SECONDARY OBJECTIVES:

I. To evaluate distant recurrence of marginal zone lymphoma at one year. II. To evaluate toxicity associated with gastric radiation therapy.

EXPLORATORY OBJECTIVES:

I. To determine if microbiome assessment can predict response to ultra-low dose radiation therapy and evaluate the differences in patient microbiome for patients who respond well and poorly to low dose radiation.

II. To determine if micro-ribonucleic acid (RNA) assessment can predict response to ultra-low dose radiation therapy and evaluate the differences in patient microRNA profiles for patients who respond well and poorly to low dose radiation.

III. To explore the role of magnetic resonance imaging (MRI) for staging gastric MALT lymphoma and for predicting response to ultra-low dose radiation therapy.

IV. To encourage optional co-enrollment on study PA18-0644 to facilitate collection and archiving of blood based biomarkers and microbiome samples for patients receiving ultra low dose radiation therapy.

OUTLINE:

Patients undergo low-dose radiation therapy over 2 fractions for 2 consecutive days in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease at 12-16 weeks post-treatment, or persistent disease at 1 year may undergo higher-dose radiation therapy at the discretion of treating physician.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

Inclusion Criteria:

• Patients 18 years or older with stage I-IV MALT lymphoma involving the stomach. Other low grade lymphomas including follicular grade I/II and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are ineligible
• Patients must have biopsy-proven disease within the stomach. Patients with clinical and/or radiographic masses will have dimensions noted prior to therapy
• Patients must have H. pylori testing which is negative within 6 months prior to treatment
• Female patients of childbearing potential must have a negative serum pregnancy test (human chorionic gonadotropin [hCG]) within 2 weeks of protocol entry
• Planned systemic therapy prior to, during, or after gastric radiation therapy is permitted however the timing of systemic therapy will be recorded and patients will be stratified according to receipt of systemic therapy
• Patients must have the ability to give informed consent
• Necessary treatment with antibiotics for reasons unrelated to gastric lymphoma is permitted however the timing and nature of the treatment will be recorded

Exclusion Criteria:

• Patients with aggressive B cell lymphoma histology, including diffuse large B cell lymphoma (DLBCL) and grade 3 follicular lymphoma
• Patients with other histologic subtypes of low grade lymphoma (other than MALT) including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or follicular lymphoma
• Patients with bulky tumors > 10 cm in any dimension
• Patients with a history of prior radiation to the stomach if re-treatment would exceed known gastric or surrounding critical structure (e.g., bowel, spinal cord) tolerance
• Patients who are pregnant
• Patients with scleroderma are ineligible