Interim PET-Guided Dose-Adapted Residual Site Radiotherapy Improves Survival in Diffuse Large B-Cell Lymphoma Patients with Partial Metabolic Response After R-CHOP: A Retrospective Cohort Analysis

Abstract Background Optimal management of diffuse large B-cell lymphoma (DLBCL) patients achieving partial remission (Deauville 5-PS 4-5) on interim PET/CT (iPET) is undefined. This study evaluated iPET-guided, dose-adapted residual site radiotherapy (RSRT) outcomes. Methods Retrospective analysis of 68 DLBCL patients with iPET 5-PS 4-5 after 4 R-CHOP cycles. 29 received 2 additional R-CHOP + risk-adapted RSRT (24Gy for 5-PS4; 40Gy for 5-PS5), while 39 received 2-4 R-CHOP cycles without RT. Results The RT cohort demonstrated significantly higher end-of-treatment complete response rates (72.4% vs 38.5%, p=0.006) and superior progression-free survival (2-year: 85.8% vs 52.9%; 5-year: 57.2% vs 44.1%; log-rank p=0.025). No overall survival difference was observed (0 deaths in RT vs non-RT cohort 2-year and 5-year OS rates of 88.1% and 77.3%; p=0.068). Multivariate analysis confirmed RT as an independent PFS protective factor (HR=0.26, 95%CI:0.09–0.79, p=0.018). Subgroup analysis revealed consistent PFS benefits across high-risk features including advanced stage, high IPI, and BCL2+ disease. RT-related toxicities were manageable (Grade 4 gastrointestinal perforation: n=1; Grade 2 pneumonitis: n=2). Conclusion IPET-guided dose-adapted residual site RT significantly enhances tumor response and PFS in DLBCL patients with suboptimal interim metabolic response, demonstrating favorable safety. This represents a promising strategy for high-risk partial metabolic responders, warranting prospective validation.