Results of RCTs that examined the efficacy of a lower compared to a higher radiotherapy dose
| Trial . | Intervention control participants . | OS, % . | FFTF, % . | PFS, % . | EFS, % . | Late AE, % . | Response, % . | Median follow-up . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| GOELAMS H 97E | Arm A (reduced-dose arm): 3 × ABVD + irradiation at 36 Gy to initially involved sites and 24 Gy to adjacent sites, the upper infra-diaphragmatic area, and the spleen (n = 89) | 97.8 ± 3.1 vs 95 ± 4.9 at 10 y (P = NS) | *88.6 ± 11.4 vs 92.6 ± 5.9 at 10 y (P = NS) | NR | NR | NR | NR | 10 y | 20 |
| GHSG HD11 | Arm A: 4 × ABVD + IFRT 30 Gy (n = 386) vs standard treatment | Arm A: 94.3 (95% CI: 91-96) at 5 y | 4 × ABVD arm at 5 y: inferiority of 20 Gy vs 30 Gy could not be excluded (n = 682), difference −4.7% (95% CI: −10.3 to 0.8) | †Arm B vs arm A: HR: 1.49; 95% CI: 1.04-2.15 (P = .03) | NR | SC: 30 Gy vs 20 Gy: 3.4 vs 4.0 (P = NS) Death: 30 Gy vs 20 Gy: 6.5 vs 6.2 | Complete response: 30 Gy vs 20 Gy: 94.5 vs 93.7 (P = NS) | 105 mo | 21 |
| Arm B: 4 × ABVD + IFRT 20 Gy (n = 395) vs Arm C | Arm B: 93.8 (95% CI: 91-96) at 5 y | ||||||||
| Arm C: 4 × BEACOPP + 30 Gy IFRT (n = 394) vs Arm D | Arm C: 94.6 (95% CI: 92-97) at 5 y | *4 × BEACOPP arm at 5 y: 20 Gy was not inferior to 30 Gy (n = 669), difference −0.8% (95% CI: −5.8 to 4.2) | |||||||
| Arm D: 4 × BEACOPP + 20 Gy IFRT (n = 395) | Arm D: 95.1 (95% CI: 92-97) at 5 y (P = NS) | ||||||||
| GHSG HD10 | Arm A: 4 × ABVD + IFRT 30 Gy (n = 346) vs Arm B | Arms A & C: 94.9 (95% CI: 92.2-96.6) at 8 y Arms B & D: 95.6 (95% CI: 93.2-97.1) at 8 y HR for death: 0.86; 95% CI: 0.49-1.53 (P = .61) | Arms B & D at 8 y: 88.6 (95% CI: 85.1-91.3) Arms A & C at 8 y: 87.8 (95% CI: 83.8-90.9) HR: 1.00 (95% CI: 0.68-1.47) Group difference at 5 y of Arms B & D vs arms A & C: −0.5 (95% CI: −3.6 to 2.6); the 7% inferiority of 20 Gy can be excluded | Arms A & C at 8 y: 88.1 (95% CI: 84.1-91.2) Arms B & D at 8 y: 88.9 (95% CI: 85.4-91.6) | NR | SC at 7.5 y: Arms A & C: 5.4 Arms B & D: 4.1 Death at 7.5 y: Arms A & C: 4.3 Arms B & D: 3.7 (P = .34) | Complete response: Arms A & C: 99.0 Arms B & D: 97.4 (P = NS) | 90 mo | 22 |
| Arm B: 4 × ABVD + IFRT 20 Gy (n = 340) vs Arm C | |||||||||
| Arm C: 2 × ABVD + IFRT 30 Gy (n = 341) vs Arm D | |||||||||
| Arm D: 2 × ABVD + IFRT 20 Gy (n = 343) | |||||||||
| EORTC-GELA H9F (favorable) | Arm A: IFRT 36 Gy + 6 × EBVP (n = 239) | 98 vs 98 vs 98 | NR | NR | 87 vs 84 vs 70 (P < .001) | NR | NR | 4 y | 15 |
| Arm B: IFRT 20 Gy + 6 × EBVP (n = 239) | |||||||||
| Arm C: no RT + 6 × EBVP (arm stopped early) (n = 130) |
| Trial . | Intervention control participants . | OS, % . | FFTF, % . | PFS, % . | EFS, % . | Late AE, % . | Response, % . | Median follow-up . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| GOELAMS H 97E | Arm A (reduced-dose arm): 3 × ABVD + irradiation at 36 Gy to initially involved sites and 24 Gy to adjacent sites, the upper infra-diaphragmatic area, and the spleen (n = 89) | 97.8 ± 3.1 vs 95 ± 4.9 at 10 y (P = NS) | *88.6 ± 11.4 vs 92.6 ± 5.9 at 10 y (P = NS) | NR | NR | NR | NR | 10 y | 20 |
| GHSG HD11 | Arm A: 4 × ABVD + IFRT 30 Gy (n = 386) vs standard treatment | Arm A: 94.3 (95% CI: 91-96) at 5 y | 4 × ABVD arm at 5 y: inferiority of 20 Gy vs 30 Gy could not be excluded (n = 682), difference −4.7% (95% CI: −10.3 to 0.8) | †Arm B vs arm A: HR: 1.49; 95% CI: 1.04-2.15 (P = .03) | NR | SC: 30 Gy vs 20 Gy: 3.4 vs 4.0 (P = NS) Death: 30 Gy vs 20 Gy: 6.5 vs 6.2 | Complete response: 30 Gy vs 20 Gy: 94.5 vs 93.7 (P = NS) | 105 mo | 21 |
| Arm B: 4 × ABVD + IFRT 20 Gy (n = 395) vs Arm C | Arm B: 93.8 (95% CI: 91-96) at 5 y | ||||||||
| Arm C: 4 × BEACOPP + 30 Gy IFRT (n = 394) vs Arm D | Arm C: 94.6 (95% CI: 92-97) at 5 y | *4 × BEACOPP arm at 5 y: 20 Gy was not inferior to 30 Gy (n = 669), difference −0.8% (95% CI: −5.8 to 4.2) | |||||||
| Arm D: 4 × BEACOPP + 20 Gy IFRT (n = 395) | Arm D: 95.1 (95% CI: 92-97) at 5 y (P = NS) | ||||||||
| GHSG HD10 | Arm A: 4 × ABVD + IFRT 30 Gy (n = 346) vs Arm B | Arms A & C: 94.9 (95% CI: 92.2-96.6) at 8 y Arms B & D: 95.6 (95% CI: 93.2-97.1) at 8 y HR for death: 0.86; 95% CI: 0.49-1.53 (P = .61) | Arms B & D at 8 y: 88.6 (95% CI: 85.1-91.3) Arms A & C at 8 y: 87.8 (95% CI: 83.8-90.9) HR: 1.00 (95% CI: 0.68-1.47) Group difference at 5 y of Arms B & D vs arms A & C: −0.5 (95% CI: −3.6 to 2.6); the 7% inferiority of 20 Gy can be excluded | Arms A & C at 8 y: 88.1 (95% CI: 84.1-91.2) Arms B & D at 8 y: 88.9 (95% CI: 85.4-91.6) | NR | SC at 7.5 y: Arms A & C: 5.4 Arms B & D: 4.1 Death at 7.5 y: Arms A & C: 4.3 Arms B & D: 3.7 (P = .34) | Complete response: Arms A & C: 99.0 Arms B & D: 97.4 (P = NS) | 90 mo | 22 |
| Arm B: 4 × ABVD + IFRT 20 Gy (n = 340) vs Arm C | |||||||||
| Arm C: 2 × ABVD + IFRT 30 Gy (n = 341) vs Arm D | |||||||||
| Arm D: 2 × ABVD + IFRT 20 Gy (n = 343) | |||||||||
| EORTC-GELA H9F (favorable) | Arm A: IFRT 36 Gy + 6 × EBVP (n = 239) | 98 vs 98 vs 98 | NR | NR | 87 vs 84 vs 70 (P < .001) | NR | NR | 4 y | 15 |
| Arm B: IFRT 20 Gy + 6 × EBVP (n = 239) | |||||||||
| Arm C: no RT + 6 × EBVP (arm stopped early) (n = 130) |
BEACOPP, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone; EBVP, epirubicin, bleomycin, vinblastine, prednisone; FFTF, freedom from treatment failure; GELA, French Adult Lymphoma Study Group; NR, not reported; NS, not significant; GOELAMS, East West Study Group of Leukemia and Other Diseases of the Blood; SC, second cancers.
Primary outcome
The single experimental arms (arms B, C, and D) were compared to the standard arm (arm A) in a Cox regression model, together with all candidate prognostic factors.