EORTC H8-F and H8-U

Background

Phase III RCT (EORTC H8). Two concurrent trials: H8-F (favorable early-stage HL, n=543) and H8-U (unfavorable early-stage HL, n=995). Tested whether combined modality therapy (CMT) could replace subtotal nodal irradiation (STNI) while reducing toxicity. Three arms in H8-F, two in H8-U.

Interventions and follow up

H8-F Arm A: 3 cycles MOPP/ABV + IFRT 36 Gy
H8-F Arm B: 3 cycles MOPP/ABV + STNI 36 Gy
H8-F Arm C: STNI 36 Gy alone
H8-U Arm A: 6 cycles MOPP/ABV + IFRT 36 Gy
H8-U Arm B: 4 cycles MOPP/ABV + STNI 36 Gy
Primary endpoint: Event-free survival and overall survival
mFollow up: Median 92 month

Results

H8-F 10-year EFS: 88% (6-cycle CMT) vs 78% (STNI alone) — CMT arms superior
H8-U 10-year EFS: 84% (6× MOPP/ABV + IFRT) vs 75% (4× + STNI), P=.001
10-year OS: 92–93% across arms — no significant differences

Adverse events

MOPP/ABV: Infertility, secondary leukemia risk, pulmonary toxicity
STNI: Higher late cardiac disease and second solid tumors
CMT + IFRT: Reduced radiation volume and RT-related late toxicity vs STNI

Conclusions

CMT (MOPP/ABV + IFRT) achieves superior or equivalent EFS vs STNI alone with reduced radiation fields. IFRT-based CMT replaced STNI as the standard for early-stage Hodgkin lymphoma.

Key Limitations

MOPP/ABV no longer used (replaced by ABVD and BEACOPP); secondary leukemia risk limits modern applicability. Extended RT fields (STNI) now historical. High RT doses (36 Gy) exceed modern standards (20–30 Gy), inflating late RT toxicity in RT arms.

Clinical Context

Landmark trial establishing CMT with involved-field RT as the new standard, replacing extended-field RT for early HL. Subsequent EORTC H9/H10 and GHSG HD10 refined the chemotherapy regimen (ABVD), RT dose (20–30 Gy), and explored RT omission in PET-negative patients.

References