Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiotherapy (IFRT). The addition of rituximab has revolutionized the treatment of DLBCL. Rituximab combined with CHOP (R-CHOP) has been established as the standard treatment for patients with DLBCL. However, the role of consolidative radiotherapy (RT) in the treatment of limited stage DLBCL in the rituximab era is controversial.

Patients and Methods: We retrospectively analyzed 108 patients with limited stage DLBCL who received R-CHOP or R-THP-COP (rituximab plus, cyclophosphamide, pirarubicin, vincristine and prednisone) regimen between June 2004 and August 2015. We compared overall survival (OS) and progression-free survival (PFS) according to the treatment. OS was calculated from the date of initiation of chemotherapy to the date of the last follow-up or death. PFS was calculated from the date of initiation of chemotherapy to the date of progression disease, death, or last contact, whichever occurred first. Survival was estimated from Kaplan-Meier curves and compared using the log-rank test. P < 0.05 was considered statistically significant. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for RT was used to account for differences in baseline characteristics.

Results: Median age at diagnosis was 66 years (19-88 years), with 61 males and 47 females. Forty-three patients (40%) had stage I, and 65 patients (60%) received consolidative RT after chemotherapy. Patients who received consolidative RT were significantly younger (65 vs 72, P < 0.01) and were more likely to have stage I disease (51% vs 23%, P < 0.01). The median number of chemotherapy cycles was 4 (range 3-8) in patients who received RT, and 6 (range 3-8) in patients who did not. Median follow-up was 4.3 years (0.3-10.9 years), and the 5-year OS (92% vs 63%, P < 0.01) and PFS (87% vs 65%, P < 0.01) were significantly higher for patients who received RT than those who did not. Using IPW adjustment, RT remained predictive of OS (HR 0.30, CI 0.13-0.72, P < 0.01) and PFS (HR 0.47, CI 0.22-0.99, P < 0.05).

Conclusion: Our results suggest that consolidative RT improves OS and PFS in patients with limited stage DLBCL in the rituximab era. Although consolidative RT seems to be gradually phased out by chemotherapy alone, it is still an important treatment strategy.