In patients with early-stage, nonbulky Hodgkin lymphoma (HL), overall survival (OS) was superior at 12 years in patients who received standard chemotherapy compared with radiotherapy in a study conducted by the National Cancer Institute of Canada's Clinical Trials Group and the Eastern Cooperative Oncology Group. The HD.6 trial enrolled 405 patients, who were followed for a median of 11.3 years. At 12 years, 94% of patients receiving ABVD (Adriamycin [doxorubicin/ hydroxydaunorubicin]/bleomycin/ vinblastine/dacarbazine) chemotherapy were alive compared with 87% receiving subtotal nodal radiation with or without chemotherapy. Deaths were reduced by 50% (P = .04) among the chemotherapy group. However, the study found that disease control was superior with radiation, with a rate of 92% versus 87% with chemotherapy, and a 91% risk of progression with chemotherapy (P = .05).
"The reason for the difference in OS is the greater number of deaths from other causes in the radiation group," said Ralph Meyer, MD, of Queen's University in Kingston, Ontario. "The long-term outcomes in patients with Hodgkin lymphoma depend on the ability to control cancer itself, but, in addition, the nature of the treatment has its own long-term effects, including the risks of developing other cancers and cardiovascular problems." Of 12 deaths in the chemotherapy arm, 6 were the result of HL or early complications, whereas 6 were related to other causes. Of the 24 deaths in the radiation arm, 4 were the result of HL or toxicity and 20 were related to other causes, including 10 second cancers. Cardiac events were also much higher in the radiation arm.
Dr Meyer acknowledged that sub total nodal irradiation is no longer standard practice. "The control arm would, today, be considered excessive and likely contributed to second cancers and cardiovascular events….but the use of radiation in this population would still include fields that would encompass the coronary arteries and potentially involve the heart and, depending on the extent of disease, substantial areas of the superdiaphragmatic structures. While the risk we saw would likely be reduced with modern strategies, we don't know the magnitude of this." Jane Winter, MD, of Northwestern University Feinberg School of Medicine, Chicago, who moderated a press briefing, commented, "Treatment of Hodgkin lymphoma is a real balance between achieving control and cure, while limiting long-term side effects. This presentation speaks to that balance and the importance of long-term follow-up in evaluating our new therapies."—CH
