Response-Adapted Omission of Radiotherapy and Comparison of Consolidation Therapy in Pediatric Classical Hodgkin Lymphoma

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In analyses from the European EuroNet-PHL-C1 study reported in The Lancet Oncology, Mauz-Körholz et al found that radiotherapy could be omitted in pediatric patients with intermediate- or advanced-stage classical Hodgkin lymphoma who had adequate response to induction with OEPA (vincristine, etoposide, prednisone, and doxorubicin) and that consolidation with COPP (cyclophosphamide, vincristine, prednisone, procarbazine) vs COPDAC (COPP with the potentially less gonadotoxic dacarbazine replacing procarbazine) produced similar outcomes, with the latter being associated with reduced gonadotoxicity.

Study Details

The study included patients aged < 18 years enrolled from sites in 16 European countries between January 2007 and January 2013. In one phase of the study, a per-protocol population of 1,287 patients (435 with intermediate-stage and 852 advanced-stage disease) received two cycles of OEPA induction. Those with morphologic and metabolic adequate response did not receive radiotherapy. The primary objective was to determine if omission of radiotherapy maintained a historical 90% event-free survival at 5 years.

In a second phase, a per-protocol population of 892 patients were randomly assigned to two (intermediate-stage patients) or four cycles (advanced-stage patients) of consolidation with COPP (n = 444) vs COPDAC (n = 448). The primary objective was to assess noninferiority of COPDAC by excluding a decrease of 8% in 5-year event-free survival.

Key Findings

Median follow-up was 66.5 months (interquartile range = 62.7–71.7 months). Among 1,287 patients assessed for response to OEPA induction, 514 (40%) had an adequate response to treatment and did not receive radiotherapy. Event-free survival at 5 years was 90.1% (95% confidence interval [CI] = 87.5%–92.7%) in these patients.

In the randomized comparison, event-free survival at 5 years was 89.9% (95% CI = 87.1%–92.8%) in the COPP consolidation group (n = 444) vs 86.1% (95% CI = 82.9%–89.4%) in the COPDAC group (difference = –3.7%, 95% CI = –8.0% to 0.6%).

Among evaluated patients, COPP was associated with higher rates of azoospermia (P < .0001) and significant follicle-stimulating hormone (FSH) elevation (P < .0001) in male patients and a higher rate of significant FSH elevation in female patients (P < .0001).

The investigators concluded, “Our results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased.”

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

Disclosure: The study was funded by Deutsche Krebshilfe, Programme Hospitalier de Recherche Clinique, Cancer Research UK, and others. For full disclosures of the study authors, visit

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