Background
Phase III RCT (UK RAPID). 420 patients with stage IA or IIA non-bulky Hodgkin lymphoma from 106 UK centers. All patients received 3 cycles ABVD followed by PET scan. PET-negative patients (n=420 of 571 enrolled) were randomized to IFRT or no further treatment. First large randomized trial to test RT omission in PET-negative early-stage HL. Median follow-up 60 months.
Interventions and follow up
Arm A: IFRT 30 Gy in 15–20 fractions (n=211)
Arm B: No further treatment — observation only (n=209)
Primary endpoint: Non-inferiority of no RT vs IFRT for 3-yr PFS (non-inferiority margin 7%)
mFollow up: 60 month
Arm B: No further treatment — observation only (n=209)
Primary endpoint: Non-inferiority of no RT vs IFRT for 3-yr PFS (non-inferiority margin 7%)
mFollow up: 60 month
Results
3-yr PFS: 94.6% (IFRT) vs 90.8% (no RT), absolute difference 3.8%
Non-inferiority in per-protocol analysis: Met (one-sided 95% CI upper bound 6.3%, within 7% margin, P=.0027)
Non-inferiority in ITT analysis: Not met
OS at 3 years: 97% (IFRT) vs 99% (no RT) — no significant difference
Non-inferiority in per-protocol analysis: Met (one-sided 95% CI upper bound 6.3%, within 7% margin, P=.0027)
Non-inferiority in ITT analysis: Not met
OS at 3 years: 97% (IFRT) vs 99% (no RT) — no significant difference
Adverse events
Main adverse events: IFRT arm: acute skin reactions, esophagitis, pneumonitis in small proportions. No RT arm: no radiation-related effects. No significant difference in OS or second malignancy at this follow-up.
Conclusions
In PET-negative early-stage HL after 3 cycles ABVD, RT omission results in a small (3.8%) absolute reduction in 3-year PFS but non-inferiority was met only in per-protocol analysis. Given excellent OS in both arms, RT omission is a reasonable option for selected PET-negative patients, particularly those for whom long-term RT toxicity is the primary concern.
Key Limitations
Key Limitations: Non-inferiority was met only in per-protocol analysis, not ITT — a methodologically important distinction. Absolute PFS difference (3.8%) may be clinically significant in young patients. Median follow-up 60 months is insufficient to assess lifetime second malignancy risk from RT. Direct comparison with H10 is limited by different chemotherapy regimens (3 vs 2 cycles ABVD) and PET platforms.
Clinical Context
UK RAPID supports the option of RT omission in carefully selected PET-negative early-stage HL patients who prioritize avoiding long-term RT toxicity. However, the non-inferiority was marginal and not met in ITT analysis. NCCN guidelines acknowledge RT omission as an option in PET-negative patients; ESMO and GHSG guidelines generally still recommend CMT as standard, with RT omission discussed as an alternative given OS equivalence.
References
References: Radford J et al, NEJM 2015 (UK RAPID)