Association of Overall Survival Benefit of Radiotherapy with Progression-Free Survival after Chemotherapy for Intermediate and High Risk Diffuse Large B-cell Lymphoma: a Systematic Review and Meta-Analysis

ObjectiveTo evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL).MethodsA 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.ResultsFor both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) 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 increased ∼18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four 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 ∼21% at PFS ≤ 40%, with pooled HROS 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%.ConclusionWe demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.