Consolidative Radiation Therapy Improves Progression-Free Survival in DLBCL

Authors of a bi-institutional, retrospective study on 188 patients with stage III-IV diffuse large B-cell lymphoma (DLBCL) reported that consolidative radiation therapy (RT) improved progression-free survival (PFS) in both bulky and nonbulky disease.

They noted that most patients with DLBCL present with stage III-IV disease. Modern therapies—especially those that include rituximab, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone)—have “contributed greatly to improving the survival rate,” they wrote

The study, with results published in Cureus, was conducted because the role of consolidative RT in advanced-stage DLBCL “is not fully established.” Use of RT has been questioned, they wrote, “particularly as it exposes patients to a separate array of potential toxicities,” in addition to systemic therapy. However, since the 10-year overall survival (OS) rate for patients with stage II-IV DLBCL receiving R-CHOP alone is approximately 43.5%, the authors argued, “further efforts are warranted to improve outcomes” for patients with advanced disease.

The investigators addressed this knowledge gap by recruiting treatment-naive patients whose stage III-IV DLBCL (bulky or nonbulky disease) was diagnosed between April 1999 and January 2011and who had a complete clinical response to systemic therapy. Patients who had central nervous system involvement or those with relapsed or refractory disease were excluded from the study.

Thirty-six percent of patients presented with stage III DLBCL, and 64% with stage IV disease. Most (79%) had received R-CHOP as their systemic therapy, 9% were treated with another rituximab-based regimen, and 12% were treated without rituximab.

Thirty-six percent of patients received consolidative RT after systemic therapy, and 64% received only systemic therapy. The median follow-up time was 4.1 years.

Patients who received consolidative RT were more likely to have bulky disease (69%) vs those treated with systemic therapy alone (53%). No other significant between-group differences in patient characteristics were observed.

According to Kaplan-Meier curves constructed by the investigators, the patients receiving consolidative RT showed improved PFS, OS, and local control compared with the chemotherapy group. Median PFS in the chemotherapy group was 4.9 years, and OS was 6.6 years. Neither median PFS nor OS were reached in the consolidative RT group, and median time to local failure was not reached for either group.

The authors said their analysis suggested the addition of RT provided a 36.5% absolute benefit in 5-year PFS (85.9% in RT group vs 49.2% in chemotherapy only group), a 14.5% absolute benefit in 5-year OS (87.4% vs 72.9%), and a 37.0% absolute benefit in five-year local control (91.9% vs 54.9%).

In univariate analysis, the authors said, the use of consolidative RT was associated with a significant improvement in PFS (HR, 0.22).In multivariate analysis adjusting for differences in International Prognostic Index, tumor size, systemic therapy regimen, and extranodal involvement, the association between consolidative RT and PFS persisted (HR, 0.23; 95% CI, 0.10-0.52), whereas the association between RT and OS lost statistical significance. The association between RT and local control persisted (HR, 0.20; 95% CI, 0.07-0.59) when adjusted for study site, tumor size, and number of cycles.

The investigators defined bulky disease in this study as 5 cm or larger in tumor diameter for the largest mass observed upon initial staging imaging, noting, “The definition of bulky disease from the standpoint of consolidation is a topic of ongoing debate, but the existing body of literature points to tumor size affecting treatment outcomes.”

In both bulky and nonbulky disease, PFS significantly improved in patients receiving consolidative RT vs systemic therapy alone. No differences in OS were observed.

“For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with the nonbulky disease,” the investigators concluded, adding their results “corroborate earlier retrospective studies.”

They acknowledged limitations including varied RT dosing across patients and lack of imaging standardization.

Although improvements in survival outcomes provided by rituximab have “led some to question the utility of consolidative RT,” the authors said that their study provides evidence supporting the use of consolidative RT in patients with advanced-stage DLBCL and complete response after chemotherapy and contributes to a growing body of research on the subject.

Reference

Syed YA, Jiang C, Switchenko J, et al. Improved progression-free survival for bulky and nonbulky advanced stage diffuse large B-cell lymphoma with consolidative radiation therapy: a bi-institutional analysis. Cureus. Published online August 11, 2021. doi:10.7759/cureus.17107