Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma: A systematic review and meta-analysis

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) PFS ) and OS HR (HROS) OS ) at trial level ( r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens ( r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns ( > 80%, > 60-80%, > 40-60%, and <= 40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from <= 5% at PFS > 80% to about 21% at PFS <= 40%, with pooled HROS OS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS <= 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.