Background
Phase III, open-label RCT (Children's Oncology Group; n=1,712) in patients ≤21 years with intermediate-risk classical Hodgkin lymphoma (stage IA/IIA without bulky disease, or stage IIIA). The trial tested response-adapted therapy aimed at reducing RT exposure in children without compromising disease control.
Interventions and follow up
Induction (all): 2 cycles ABVE-PC (doxorubicin 25mg/m², bleomycin 10mg/m², vincristine 1.4mg/m², etoposide 75mg/m², prednisone 40mg/m², cyclophosphamide 600mg/m²)
Arm A (RER + IFRT): ABVE-PC × 4 total cycles → 21 Gy IFRT to involved sites
Arm B (RER, chemo only): ABVE-PC × 4 cycles → no RT; slow early responders (SER) received DECA salvage + IFRT (non-randomized)
Primary endpoint: 4-year EFS in rapid early responders (non-inferiority margin −5%)
Median follow up: 6.7 years
Arm A (RER + IFRT): ABVE-PC × 4 total cycles → 21 Gy IFRT to involved sites
Arm B (RER, chemo only): ABVE-PC × 4 cycles → no RT; slow early responders (SER) received DECA salvage + IFRT (non-randomized)
Primary endpoint: 4-year EFS in rapid early responders (non-inferiority margin −5%)
Median follow up: 6.7 years
Results
4-year EFS (RER + IFRT): 87.9%
4-year EFS (RER, chemo only): 84.3% — difference 3.6%, 90% CI lower bound −7.0% (non-inferiority not met)
4-year OS: ≥98% both arms — no OS difference
SER outcomes (DECA + IFRT): 4-year EFS 75.1%
CMR-RER subgroup (PET-negative) chemo-only: 4-year EFS 85.7% (exploratory)
4-year EFS (RER, chemo only): 84.3% — difference 3.6%, 90% CI lower bound −7.0% (non-inferiority not met)
4-year OS: ≥98% both arms — no OS difference
SER outcomes (DECA + IFRT): 4-year EFS 75.1%
CMR-RER subgroup (PET-negative) chemo-only: 4-year EFS 85.7% (exploratory)
Adverse events
Radiation/late: RT arm long-term secondary malignancy risk (thyroid, breast in females)
Chemotherapy: Bleomycin grade ≥3 pulmonary toxicity ~2%; gonadal toxicity lower with ABVE-PC than MOPP-era regimens; chemo-only arm higher relapse rate
Chemotherapy: Bleomycin grade ≥3 pulmonary toxicity ~2%; gonadal toxicity lower with ABVE-PC than MOPP-era regimens; chemo-only arm higher relapse rate
Conclusions
RT omission did not achieve pre-specified non-inferiority in intermediate-risk pediatric cHL: the 90% CI crossed the −5% margin. The absolute 3.6% EFS difference weighed against lifetime RT toxicity (breast/thyroid cancer) remains debated. SER intensification with DECA rescue is feasible.
Key Limitations
Non-inferiority margin was not met though the absolute EFS difference was small. IFRT is now replaced by INRT/ISRT with substantially reduced volumes and toxicity. The CMR-RER PET-negative subgroup analysis was exploratory; the subsequent AHOD1408 specifically tested PET-adapted RT omission. Response assessment relied partly on CT-era criteria, limiting comparability to modern PET-based staging.
Clinical Context
AHOD0031 established response-adapted treatment principles in pediatric intermediate-risk cHL. Subsequent trials (AHOD1331; EuroNet-PHL-C2) use PET2 response to guide RT omission. AHOD1331 established brentuximab vedotin + AVD as superior in high-risk pediatric cHL. ASCO/COG-aligned pediatric practice continues to individualize RT based on early response.