What is the recommended initial treatment for stage I diffuse large B‑cell lymphoma (DLBCL) germinal‑center B‑cell (GCB) subtype limited to a single anatomic site?

Treatment of Stage I Diffuse Large B-Cell Lymphoma (GCB Subtype)

For stage I DLBCL with germinal center B-cell (GCB) subtype, administer 6 cycles of R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone every 21 days) with consolidation involved-site radiotherapy to any bulky disease sites. 1, 2, 3

Treatment Algorithm Based on Age

Patients Under 60 Years

• Deliver 6 cycles of R-CHOP-21 plus radiotherapy to sites of bulky disease (typically >7.5-10 cm) 1, 2, 3
• This recommendation is based on the MINT study demonstrating efficacy in young low-intermediate risk patients 1, 2
• An alternative option is R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin, prednisolone) every 2 weeks with sequential consolidation, which showed superior survival compared to 8 cycles of R-CHOP, though radiotherapy was omitted in that trial 4, 1, 2

Patients Aged 60-80 Years

• Administer 6 cycles of R-CHOP-21 for localized stage I disease 1, 2, 3
• Eight cycles may be used for more extensive stage II disease, but 6 cycles is typically sufficient for true stage I 1, 2
• Consolidation radiotherapy provides no proven benefit in the rituximab era for this age group with localized disease 4, 2

Patients Over 80 Years

• Perform comprehensive geriatric assessment before initiating treatment to determine fitness 2
• Healthy patients can receive standard R-CHOP up to age 80 2
• For frail patients over 80, use R-miniCHOP (attenuated chemotherapy with rituximab) 2
• Consider substituting doxorubicin with etoposide or liposomal doxorubicin in patients with cardiac dysfunction 2

Critical Pre-Treatment Measures

Tumor Lysis Syndrome Prevention

• Administer prednisone 100 mg orally daily for 5-7 days as "prephase" treatment before starting R-CHOP if any concern for high tumor burden 1, 2, 3
• Ensure aggressive hydration 3
• Consider prophylactic allopurinol or rasburicase in highest-risk patients 3

Supportive Care During Treatment

• Use prophylactic G-CSF (granulocyte colony-stimulating factor) to prevent febrile neutropenia, particularly in elderly patients and after any episode of febrile neutropenia 1, 2
• Avoid dose reductions for hematological toxicity whenever possible, as this compromises cure rates 1, 2, 3
• Dose reductions should only occur for severe, life-threatening toxicity 2

Response Assessment Strategy

• Repeat PET/CT after 3-4 cycles to assess mid-treatment response 1, 2, 3
• Perform end-of-treatment PET/CT using the 5-point Deauville scale to define complete remission 1, 2, 3
• Deauville score 1-3 indicates complete metabolic response 3
• Deauville score 4-5 may warrant consideration of consolidation radiotherapy even in younger patients 3

Radiotherapy Decision-Making

The role of radiotherapy in stage I DLBCL is nuanced and depends on multiple factors:

• For patients under 60 years with bulky disease, consolidation involved-site radiotherapy after 6 cycles of R-CHOP-21 is recommended 1, 2, 3
• For patients 60-80 years, radiotherapy showed no proven benefit in the rituximab era for localized disease 4, 2
• Consider radiotherapy for PET-positive residual disease (Deauville 4-5) after chemotherapy completion regardless of age 3
• Modern involved-site radiotherapy techniques have minimal long-term toxicity, making risk-benefit assessment favorable in selected cases 5

Special Considerations for GCB Subtype

While GCB subtype DLBCL generally has better prognosis than ABC subtype, treatment recommendations remain the same:

• GCB DLBCL shows better response to standard R-CHOP chemotherapy compared to non-GCB subtypes 6
• Complete response rates after 6 cycles are higher in GCB subtype (62.5% in one study) 6
• Despite better prognosis, do not reduce treatment intensity based solely on GCB classification 7, 8
• Molecular subtyping is important for prognostication but does not currently change first-line therapy selection 7, 8

Common Pitfalls to Avoid

• Do not use R-CHOP-14 (every 14 days) instead of R-CHOP-21, as dose-dense scheduling showed no survival advantage and is not recommended 4, 2
• Do not reduce chemotherapy doses after prephase treatment due to hematological concerns unless absolutely necessary 1, 2
• Do not omit radiotherapy in young patients with bulky stage I disease, as this compromises disease control 1, 2, 3
• Do not skip comprehensive geriatric assessment in patients over 80 before committing to full-dose therapy 2
• Do not assume limited-stage disease means abbreviated treatment is always safe—4 cycles may be insufficient for some patients 5

Follow-Up Protocol

• History and physical examination every 3 months for year 1 1, 3
• Every 6 months for years 2-3 1, 3
• Annually thereafter 1, 3
• Monitor for secondary malignancies and long-term chemotherapy side effects 3