RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Comparing results of diagnostic procedures, such as PET scan and CT scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

PURPOSE: This phase II trial studies how well PET-directed chemotherapy works in treating patients with limited-stage diffuse large B-cell lymphoma.

OBJECTIVES:

Primary

• To assess the 5-year progression-free survival (PFS) rate in patients with newly diagnosed limited-stage diffuse, large B-cell lymphoma (DLBCL) using positron emission tomography (PET)/CT scan to direct therapy after 3 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP).

Secondary

• To evaluate PFS within the PET-positive (+) and PET-negative (-) subgroups of patients with newly diagnosed limited-stage DLBCL.
• To evaluate toxicity of the protocol treatments in this patient population.
• To evaluate the response probability in this patient population.
• To evaluate overall survival in the overall population, and within the PET+ and PET- subgroups.
• To estimate the rate of upstaging at baseline by PET/CT at baseline among patients newly diagnosed with limited-stage DLBCL by CT imaging and to describe outcomes in patients upstaged by PET/CT at baseline to advanced DLBCL.
• To describe outcomes in the subgroup of patients upstaged by PET/CT.
• To evaluate the association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to whether the patient was upstaged to advanced stage DLBCL, based on local review of the baseline PET/CT (yes vs no).

Chemotherapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV over 30-60 minutes, vincristine sulfate IV, and doxorubicin hydrochloride IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for 3* courses. NOTE: *Patients found to have advanced stage DLBCL based on local review of the baseline PET scan receive 6 courses of R-CHOP.

FDG/PET - Radiotherapy: Patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scan at baseline, on days 15-18 of course 3, and at 12 weeks after completion of course 3. Patients with complete response (PET scan negative) receive one additional course of R-CHOP as above. Patients with partial response (PET scan positive) undergo involved-field radiotherapy (IFRT) 5 days a week for approximately 4-5 weeks.

Monoclonal antibody: Beginning 3-6 weeks after completion of IFRT, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes and rituximab IV on day 1 and on day 7, 8, or 9.

Patients may undergo blood sample collection at baseline for correlative studies. Bone marrow tissue samples may be also collected for correlative studies.

After completion of study therapy, patients are followed up every 6 months for 2 years and then yearly for 5 years.

DISEASE CHARACTERISTICS:

• Patients must have biopsy-proven diffuse large B-cell lymphoma (DLBCL)

  • Adequate sections or a paraffin block from the original diagnostic specimen must be submitted for review by the lymphoma pathology group
  • Lymphoma must express CD20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections
  • Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible

• Patients must have non-bulky stage I or II disease by Ann Arbor classification

  • This staging excludes FDG-PET evaluation
  • Patients who have stage I or II non-bulky disease on diagnostic CT scan, but are upstaged to stage III or IV based on FDG-PET evaluation, are also eligible

• Patients must have a diagnostic quality contrast-enhanced CT scan of the chest, abdomen, and pelvis AND baseline FDG-PET scan performed within 28 days prior to registration

  • Low-resolution "localization" CT scans performed as part of a combined PET/CT scan are not adequate for enrollment or response determination on this protocol
  • If a patient has an allergy to CT contrast, then a non-enhanced CT will be acceptable

• Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

  • Any laboratory or radiographic tests performed to assess CNS involvement must be negative and must be performed within 42 days prior to registration

• Patients may have either measurable or evaluable limited-stage DLBCL

  • Patients rendered free of measurable or evaluable disease by virtue of biopsy (resection) are also eligible
  • If patient has measurable disease it must be documented on the Lymphoma Baseline Tumor Assessment Form (Form #15187)
  • All measurable disease must be assessed within 28 days prior to registration
  • Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration

• Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Absolute neutrophil count (ANC) ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert syndrome)

• Patients must not be pregnant or nursing

• Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study period

• Patients must not be known to be HIV-positive

• No other prior malignancy is allowed except for the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • In situ cervical cancer
  • Adequately treated stage I or II cancer from which the patient is currently in complete remission
  • Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• Patients must not have received prior chemotherapy, radiotherapy, or antibody therapy for lymphoma