As reported in The Lancet Oncology by Mauz-Körholz et al, children and adolescents with early-stage classical Hodgkin lymphoma enrolled in the EuroNet-PHL-C1 study who had an adequate response to an OEPA chemotherapy regimen (vincristine, etoposide, prednisone, and doxorubicin) and did not receive subsequent radiotherapy did not achieve the target 5-year event-free survival rate; the 5-year rate was somewhat higher in patients with inadequate response to OEPA who received radiotherapy.

Study Details

The intent-to-treat population for the current analysis consisted of 713 patients aged < 18 years with newly diagnosed stage IA, IB, or IIA classical Hodgkin lymphoma enrolled at sites in 16 European countries between January 2007 and January 2013. Patients received two 28-day cycles of OEPA consisting of vincristine at 1.5 mg/m² capped at 2 mg on days 1, 8, and 15; etoposide at 125 mg/m² on days 1 to 5; prednisone at 60 mg/m² on days 1 to 15; and doxorubicin at 40 mg/m² on days 1 and 15. Adequate response was defined as partial morphological remission or greater and negative positron-emission tomography findings. Patients with adequate response did not receive radiotherapy; those without adequate response received involved-field radiotherapy at a total dose of 19.8 Gy, usually in 11 fractions of 1.8 Gy per day.

The primary endpoint was event-free survival. The primary objective was maintaining a 5-year event-free survival rate of 90% in patients with an adequate response to OEPA without subsequent radiotherapy.

Event-Free Survival

Median follow-up was 63.3 months (interquartile range = 60.1–69.8 months). Among the 440 patients with adequate response to OEPA who did not receive radiotherapy, 5-year event-free survival was 86.5% (95% confidence interval [CI] = 83.3%–89.8%), which failed to meet the 90% target rate.

In 273 patients without adequate response to OEPA who received radiotherapy, 5-year event-free survival was 88.6% (95% CI = 84.8%–92.5%), with the 95% confidence interval including the 90% target rate.

Subgroups with 5-year recurrence-free survival ≥ 90% were:

• Those without risk factors (bulky disease or elevated erythrocyte sedimentation rate; n = 272, 90.2%)
• Those with undetermined risk factors (n = 190, 91.3%)
• Those with adequate response to OEPA and undetermined risk factors (n = 125, 91.8%)
• Those with inadequate response to OEPA without risk factors (n = 89, 94.0%)
• Those with inadequate response to OEPA with undetermined risk factors (n = 64, 90.2%).

Adverse Events

The most common grade 3 or 4 adverse events were neutropenia (88%) and leukopenia (61%); the most common nonhematologic grade 3 or 4 events were infection (6%) and pharyngitis/stomatitis (4%). No treatment-related adverse events led to discontinuation of treatment. Among late toxicities, thyroid gland disorders of any grade were reported in 3% of patients with adequate response to OEPA and in 20% of those with inadequate response who received radiotherapy; cardiovascular disorders occurred in 2% vs 3% of patients. No treatment-related deaths occurred.

The investigators concluded, “On the basis of all the evidence, radiotherapy could be omitted in patients with early-stage classical Hodgkin lymphoma and an adequate response to OEPA, but patients with risk factors might need more intensive treatment.”

William H. Wallace, MD, of the Department of Paediatric Haematology and Oncology, Royal Hospital for Children and Young People, University of Edinburgh, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder, Programme Hospitalier de Recherche Clinique, Cancer Research UK, and others. For full disclosures of the study authors, visit thelancet.com.