Table 1.

Pivotal trials investigating the use of radiotherapy in patients with DLBCL. Trial characteristics and outcomes are provided. Details on randomization focus on radiotherapy questions. Outcomes for the RICOVER-60 trial refer to the best arm of the 2×2 design (6×R-CHOP)

Study	Patients	n	RT indication	Randomization	Dose	EFS	PFS/TTP	OS	Key message
UNFOLDER ([5] interim analysis)	18–60 years aaIPI 0–1	285	Bulk ($\ge$7.5 cm) Extranodal	RT vs. no RT	39.6 Gy	3‑year: 68% vs. 84% (p = 0.001)	3‑year: 89% vs. 81% (n. s.)	3‑year: 93% vs. 93% (n. s.)	RT reduces PR rate triggering additional treatments
RICOVER-60 [6]	61–80 years	1222	Bulk ($\ge$7.5 cm) Extranodal	No RT randomization	36 Gy	3‑year: 66.5%	3‑year: 73.4%	3‑year: 78.1%	Establishment of 6×R-CHOP as standard of care
OPTIMAL>60 ([8] interim analysis)	61–80 years	187	PET-positive patients with initial bulk ($\ge$7.5 cm)	Comparison to RICOVER-60	39.6 Gy	–	2‑year: 79% vs. 75% (n. s.)	2‑year: 88% vs. 78% (n. s.)	RT may be limited to PET-positive patients
Freeman et al. [10]	$\ge$ 18 years Advanced stages	723	PET-positive patients (Deauville: 4–5) after 6–8 cycles of R‑CHOP	None Retrospective comparison	30–40 Gy	–	3‑year: 83% (PET-NEG) vs. 76% (PET-POS + RT; n. s.) vs. 34% (PET-POS-RT; p < 0.001)	3‑year: 87% (PET-NEG) vs. 80% (PET-POS + RT) vs. 44% (PET-POS-RT)	RT may be limited to PET-positive patients. Bulky disease ($\ge$ 10 cm), skeletal or craniofacial involvement were no risk factors independent from PET status

aaIPI age-adjusted international prognostic index, EFS event-free survival, Gy Gray, n. s. not significant, OS overall survival, PET positron emission tomography, PET-NEG PET-negative patients after immunochemotherapy, PET-POS + RT PET-positive patients after immunochemotherapy with consolidative radiotherapy, PET-POS-RT PET-positive patients after immunochemotherapy without consolidative radiotherapy, PFS progression-free survival, R‑CHOP rituximab, cyclophosphamide, doxorubicin, vincristine, predniso(lo)ne, RT radiotherapy, TTP time to progression