R-CHOP with or without IF-XRT

R-CHOP (four to six cycles).

R-CHOP (three to six cycles) + IF-XRT.

In a randomized prospective trial of 334 patients with nonbulky (≤7 cm) stage I or stage II DLBCL, after receiving four to six cycles of R-CHOP-14 (R-CHOP delivered every 2 weeks), patients were randomly assigned to undergo 40 Gy of radiation therapy or no radiation therapy.[9]

In a randomized prospective trial of 334 patients with nonbulky (≤7 cm) stage I or stage II DLBCL, after receiving four to six cycles of R-CHOP-14 (R-CHOP delivered every 2 weeks), patients were randomly assigned to undergo 40 Gy of radiation therapy or no radiation therapy.[9]

After a median follow-up of 64 months, the 5-year event-free survival rate (89%–92%; P = .18) and 5-year overall survival (OS) rate (92%–96%; P = .32) were the same.[9][Level of evidence A1]Similar to the results of randomized studies of radiation therapy in the era before rituximab, radiation therapy can be deferred in patients with nonbulky early-stage disease. For patients unable to tolerate prolonged-course chemotherapy, three cycles of R-CHOP plus radiation therapy has produced equivalent results based on single-arm retrospective trials.[8]

In a randomized prospective trial (NCT00278421) of 592 patients younger than 60 years with nonbulky (<7.5 cm) stage I or stage II DLBCL, patients were randomly assigned to receive either four or six cycles of R-CHOP (with an extra two cycles of rituximab after four cycles).[10]

In a randomized prospective trial (NCT00278421) of 592 patients younger than 60 years with nonbulky (<7.5 cm) stage I or stage II DLBCL, patients were randomly assigned to receive either four or six cycles of R-CHOP (with an extra two cycles of rituximab after four cycles).[10]

With a median follow-up of 66 months, the 3-year progression-free survival (PFS) rate was 96% (95% confidence interval [CI], 94%−99%) for patients who received four cycles of R-CHOP, which was 3% better (lower limit of one-sided 95% CI was zero) than the PFS rate for patients who received six cycles, establishing noninferiority for the four-cycle regimen.[10][Level of evidence B1]

A retrospective analysis at Memorial Sloan Kettering Cancer Center between 2001 and 2015 included 341 patients with stage I disease. The analysis found that 66% of patients had an extranodal presentation. After R-CHOP (or a similar regimen), with or without radiation therapy, the 5-year disease-free survival rate was 77%, and the 5-year OS rate was 94%.[11][Level of evidence C3] A multivariate analysis suggested that radiation therapy may improve outcomes for patients with extranodal disease that is positron emission tomography (PET)–positive at the end of therapy. This hypothesis needs confirmation in a prospective randomized trial.[11]