Background
Phase III RCT (EORTC/LYSA/FIL H10). N=1,950 early-stage Hodgkin lymphoma (H10-F favorable, n=749; H10-U unfavorable, n=1,201), 16 countries. PET-guided design testing whether involved-node RT can be safely omitted in PET-negative patients after 2 cycles ABVD. Standard combined-modality therapy (CMT) vs experimental PET-adaptive arm. Stopped early at interim analysis for futility of RT omission.
Interventions and follow up
Arm A (standard CMT): ABVD x 3 (favorable) or x 4 (unfavorable) + involved-node RT 30 Gy regardless of interim PET
Arm B (experimental PET-adaptive): ABVD x 2; if PET-negative continue ABVD x 1-2 more, no RT; if PET-positive escalate to BEACOPP x 2 + involved-node RT 30 Gy
Primary endpoint: Non-inferiority of experimental arm for PFS
mFollow up: 1.1 yr at early stopping (updated to 5 yr in Andre 2017)
Arm B (experimental PET-adaptive): ABVD x 2; if PET-negative continue ABVD x 1-2 more, no RT; if PET-positive escalate to BEACOPP x 2 + involved-node RT 30 Gy
Primary endpoint: Non-inferiority of experimental arm for PFS
mFollow up: 1.1 yr at early stopping (updated to 5 yr in Andre 2017)
Results
5-yr PFS favorable (standard vs experimental no RT): 99.0% vs 87.1% — non-inferiority not met
5-yr PFS unfavorable (standard vs experimental): 92.1% vs 89.6% — non-inferiority not met
OS: No significant difference between arms (salvage therapies effective)
5-yr PFS unfavorable (standard vs experimental): 92.1% vs 89.6% — non-inferiority not met
OS: No significant difference between arms (salvage therapies effective)
Adverse events
Disease control: Experimental arm (no RT) had significantly higher progression/relapse rates
Hematologic: PET-positive patients escalated to BEACOPP had higher hematologic toxicity
RT-related: Standard CMT arm had RT-related acute and chronic effects
Hematologic: PET-positive patients escalated to BEACOPP had higher hematologic toxicity
RT-related: Standard CMT arm had RT-related acute and chronic effects
Conclusions
RT omission in PET-negative early-stage Hodgkin lymphoma yields significantly inferior PFS vs standard CMT (ABVD + involved-node RT), even when interim PET is negative after 2 cycles. Standard CMT with involved-node RT remains superior for disease control in early-stage HL.
Key Limitations
Stopped early for superiority of standard arm; long-term second-malignancy risk from RT not captured. Only 2 cycles ABVD before PET; longer chemotherapy before PET may identify more true responders. OS equivalence suggests salvage therapy is highly effective for PET-negative relapsers without RT, but at cost of added treatment burden.
Clinical Context
H10 showed omitting RT in PET-negative patients yields inferior PFS, in contrast to UK RAPID (which suggested non-inferiority); discordance partly reflects different chemotherapy regimens and PET timing. ESMO generally recommends CMT (2 cycles ABVD + 20-30 Gy ISRT) as standard, with RT omission considered investigational or reserved for select patients unwilling to accept RT-related late risks.
References