The overarching goals of this study are to measure levels of circulating tumor DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL), to assess the change in ctDNA during treatment in order to prospectively identify markers of treatment failure, and to use ctDNA as a future tool for response adapted therapy.

The long-term objective of this proposal is to determine the correlation between FDG-PET and MRD, as measured by ctDNA in patients with early stage DLBLC.

Patients will be treated with standard chemoimmunotherapy and radiation based on the recently completed SWOG S1001 study, however no radioimmunotherapy will be used (NCT01359592). Response to treatment will be determined by contemporary Deauville criteria. Assessment of ctDNA (non-invasive disease monitoring) will be determined at diagnosis and will continue at pre-defined specific time points after therapy is complete.

Inclusion Criteria:

• Previously untreated limited stage non bulky DLBCL; defined as limited stage by routine staging criteria in lymphoma involving FDG-PET and bone marrow biopsies (the Lugano criteria)[21]
• Patients with grade 3B follicular lymphoma and transformed indolent lymphoma are included
• Ages ≥ 18
• Measurable disease, assessable by radiographic examination with FDG-PET showing involvement
• Access to archived or fresh/frozen tumor biopsies
• No uncontrolled medical comorbidities
• Adequate cardiac function (EF > or equal to 50%), no unstable angina
• Adequate renal function (GFR > 60)
• Adequate liver function (liver function tests should be no greater than 2 x upper limit of normal) including normal bilirubin levels, no greater than 2 x upper limit of normal unless patient has a history of Gilbert's disease
• Adequate marrow reserves as indicated by complete blood count in the judgment of the treating investigator

Exclusion Criteria:

• Pregnancy, positive serum HCG within 28 days of enrollment, or breast-feeding
• Bulky disease greater than 10 cm in any dimension