When treating a patient with classic early stage diffuse large B-cell lymphoma (Stage I/II), when is it appropriate for patients to receive 3 versus 6 cycles of R-CHOP chemotherapy when the treatment is followed by ISRT?

The SWOG 8736 study included patients with stage I (bulky or non-bulky) and nonbulky stage II aggressive non-Hodgkin lymphomas (mostly DLBCL). Bulky was defined as a mediastinal mass >1/3 maximal chest diameter or any mass > 10 cm. Patients were randomized to 8 cycles of CHOP or 3 cycles of CHOP + RT. Survival and failure-free survival at 5 years favored 3 cycles + RT and there was less toxicity with this approach. However, with longer follow-up there were excessive systemic failures in the abbreviated chemotherapy arm and the FFS curves crossed at 7 years and the OS curves crossed at 9 years. Although never published in manuscript form, these data suggest that 3 cycles of CHOP (and likely R-CHOP) is inadequate therapy for some patients with stage I-II DLBCL. The risk of relapse and death were related to the number of risk factors on the stage-adjusted IPI with patients having no risk factors (stage I, age < 60, normal serum LDH, ECOG PS 0-1) doing very well.

SWOG 0014 was a phase II study that enrolled patients with aggressive NHLs (mostly DLBCL) to 3 cycles of R-CHOP + RT. Patients were eligible if they had at least one risk factor in the stage-adjusted IPI. Outcomes were excellent at 4 years (OS 92%) and significantly better than the historical group of patients from SWOG 8736. An update, to my knowledge, has not been published in manuscript form.

While there is inevitable variation in clinical practice, with limited randomized data to guide practice, our general philosophy is to treat:

A. Non-bulky stage I patients with 0-1 risk factors (elevated LDH, age > 60, PS > 1)- R-CHOP X 3 + 30 Gy.

B. Non-bulky stage II patients with 0-1 risk factors- R-CHOP X 4 + 30 Gy.

C. Bulky patients and those with multiple risk factors- R-CHOP X 6 + 30 Gy.