Recent phase 3 trial results indicate that children and adolescents with intermediate- or advanced-stage classical Hodgkin lymphoma who demonstrate adequate responses to certain chemotherapy regimens might safely omit radiotherapy. Study results were reported in the journal Lancet Oncology.

The open-label, phase 3 EuroNet-PHL-C1 trial ( Identifier: NCT00433459) was a titration study conducted across 186 hospital sites across Europe. In this trial, newly diagnosed patients below 18 years of age were assigned to treatment groups based on cHL stage. Treatment group 1 included patients with early disease, and this group was excluded from analysis. Treatment group 2 consisted of patients with intermediate-stage cHL, while treatment group 3 consisted of patients with advanced-stage disease.

An embedded randomized study of 2 chemotherapy regimens was also included. Within treatment groups, patients were randomly assigned 1:1 and stratified according to risk status. All patients were given induction with 2 cycles of vincristine, etoposide, prednisone, and doxorubicin (OEPA) and recommended for radiotherapy if response was inadequate. For consolidation, treatment group 2 was randomized to receive 2 cycles of either cyclophosphamide with vincristine, prednisone, and procarbazine (COPP) or COPDAC, which was COPP with dacarbazine in place of procarbazine. Treatment group 3 was randomized to receive 4 cycles of either COPP or COPDAC.

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The primary endpoint was event-free survival (EFS), with a primary objective of a 5-year EFS rate of 90% and with adequate OEPA response without radiotherapy for the titration study. The randomized comparison used a tolerance limit of -8% for 5-year EFS as the threshold to demonstrate noninferiority for COPDAC compared with COPP.

In this study, with a median follow-up of 66.5 months for per-protocol titration analysis, 435 patients were in treatment group 2 and 852 were in treatment group 3. Most patients from treatment groups 2 and 3 were randomly assigned, including 471 patients across these groups who were randomly assigned to COPP and 466 to COPDAC.

In per-protocol titration analysis, 40% of patients demonstrated adequate response and did not receive radiotherapy. This included 49% of evaluable patients in treatment group 2 and 35% of evaluable patients in treatment group 3. The 5-year EFS rate for patients who responded adequately was 90.1% (95% CI, 87.5%-92.7%).

The 5-year EFS rate for patients receiving COPP was 89.9% (95% CI, 87.1%-92.8%), and with COPDAC it was 86.1% (95% CI, 82.9%-89.4%). This equaled a difference between COPDAC and COPP for 5-year EFS of -3.7% (95% CI, -8.0%-0.6%).

The most common grade 3 or 4 adverse events were decreased neutrophils, white blood cells, and hemoglobin levels. A fatality occurred in a patient from treatment group 2 during OEPA treatment.

“We have shown that radiotherapy can safely be avoided in patients with intermediate-stage and advanced-stage disease who have an adequate response to intensified OEPA induction without compromising event-free or overall survival when treated with either COPP or COPDAC consolidation,” the study investigators concluded in their report.


Mauz-Körholz C, Landman-Parker J, Balwierz W, et al. Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, mult. Lancet Oncol. 2022;23(1):125-137. doi:10.1016/S1470-2045(21)00470-8