Radiation Therapy Dose Response in Bulky Relapsed/Refractory Large B-Cell Lymphoma

<bold>Purpose: </bold>To assess whether a radiation therapy (RT) dose affects response in bulky tumors in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). <bold>Methods and materials: </bold>Data from patients with r/r DLBCL treated with salvage- or palliative-intent RT (2008-2020) at a single institution were examined. Index lesion size >= 7.5 cm was defined as bulky. Equivalent doses in 2-Gy fractions (EQD2) were calculated to compare doses between conventional and hypofractionated (>= 2.5 Gy/fraction) schemes. Objective response rates (ORRs) were compared using nonparametric Mann-Whitney U test or Kruskal-Wallis test with Dunn's multiple comparison corrections. Freedom from local progression (FFLP) was assessed using Kaplan-Meier and Cox proportional hazard regression analyses. <bold>Results: </bold>One hundred eighty-three courses of 151 unique patients were included (salvage: 37% and palliative: 63%). Nonbulky and bulky tumors were irradiated in 109 (60%) and 74 (40%) courses, respectively. Median EQD2 was 33 Gy (IQR, 23-39 Gy) with hypofractionation in 84 (46%) cases. Of those with post-RT imaging (80%), the ORR was 59%, with a trend toward worsened ORR in bulky tumors (50% vs 65%, P = .077). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (<= 30 Gy vs >30 Gy: 27% vs 64%, P = .0073), whereas a lower EQD2 cutoff was sufficient for nonbulky tumors (<= 20 Gy vs >20 Gy: 38% vs 75%, P = .0011). On multivariable regression analysis, bulky tumor size was associated with worsened FFLP (hazard ratio, 2.07; 95% CI, 1.16-3.68; P = .014), whereas high EQD2s >30 Gy were associated with better FFLP (hazard ratio, 0.48; 95% CI, 0.25-0.93; P = .031). Bulky tumors treated with EQD2s <= 30 Gy had the lowest median FFLP (4.0 months), whereas EQD2s >30 Gy had an unreached median FFLP (P = .0047). <bold>Conclusions: </bold>Bulky r/r DLBCL tumors were associated with less favorable tumor control outcomes in the salvage and palliative settings. RT regimens with higher EQD2s (>30 Gy) should be considered if durable local control of bulky tumors is desired.