Association of Overall Survival Benefit Profile of Radiotherapy with Progression-Free Survival after Chemotherapy for Diffuse Large B-Cell Lymphoma

Abstract

Benefit of radiotherapy (RT) after chemotherapy (CT) of diffuse large B-cell lymphoma (DLBCL) remains controversial. It is unknown whether improved progression-free survival (PFS) by RT translate into an overall survival (OS) benefit. To address this question, our research comprehensively evaluated the risk-benefit assessment of RT in DLBCL through an in-depth examination of previously reported data from randomized controlled trials (RCTs) and retrospective comparative studies. After screening and quality control, this study included 7 randomized controlled trials and 52 retrospective studies of combined-modality therapy (CMT) versus CT alone. The correlation between PFS and OS was evaluated using the Pearson linear correlation coefficient at trial- and study arm-level. A risk-benefit assessment to describe the OS benefit of RT was performed in meta-analyses of pooled HROS with PFS patterns. In RCTs, strong correlations were found between HRPFS and HROS at trial-level (r = 0.876), and PFS and OS at treatment arm-level, regardless of treatments (r = 0.945-0.964 for all, CMT or CT). In retrospective studies, similar correlations between HRPFS and HROS (r = 0.639-0.650), and PFS and OS rates (r = 0.882-0.910) were observed, independent of treatments or rituximab. Adding RT into rituximab-based CT increased the average PFS rate from 63.6 ± 18.9% to 81.5 ± 10.6% (P<0.001), with differential OS benefits of RT between studies. Patients can be stratified into four PFS patterns (>80%, >60-80%, >40-60%, and ≤40%); 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. Linear analysis revealed an OS advantage of CMT over CT alone in a PFS-dependent manner. We demonstrate a varied OS benefit profile of RT upon different PFS patterns, and provide valuable evidence for making treatment decisions and designing clinical trials. Future strategies to select the use of RT will need careful tailoring in clinical practice or within RCT to optimize outcome.