Chemotherapy Alone Superior to Radiation Therapy in Prolonging Survival in Early-Stage Hodgkin’s Lymphoma

San Diego—Patients with limited-stage Hodgkin’s lymphoma who received a standard chemotherapy regimen alone had longer overall survival compared with a group that received a combination of chemotherapy and radiation treatment or radiation alone. After 12 years, 94% of patients in the chemotherapy-only arm were alive compared with 87% of patients in the other group (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.25-0.99; P=.04). Results of the multicenter, randomized, controlled trial were presented at the ASH meeting in a news conference and an oral abstract session. They were also simultaneously published online in the New England Journal of Medicine (10.1056/NEJMoa1111961). Ralph M. Meyer, MD, director of the National Cancer Institute of Canada’s Clinical Trials Group and the study’s lead author, said most previous trials followed up with patients for 4 to 6 years and only assessed disease control. However, Dr. Meyer noted long-term outcomes in this population depended on controlling the cancer, but the treatments patients received had long-term effects that were not typically taken into consideration. The trial, which began in January 1994, enrolled 405 patients who had previously untreated stage IA or IIA nonbulky Hodgkin’s lymphoma. Six patients (3 in each group) were considered to be ineligible before the randomization period began. The remaining 399 patients received a chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or subtotal nodal radiation therapy with or without ABVD. According to Dr. Meyer, the authors stopped enrollment in April 2002 after a European study found favorable outcomes with involved-field radiation therapy compared with subtotal nodal radiation therapy. Results after 5 years of follow-up were presented at the 2003 ASH meeting, which Dr. Meyers said indicated there was no difference in overall survival between the groups. After 12 years, the rates of freedom from disease progression were 87% in the ABVD alone group and 92% in the radiation therapy group (HR, 1.91; 95% CI, 0.99-3.69; P=.05). There was no statistically significant difference in event-free survival: 85% in the ABVD alone group and 80% in the radiation therapy group (HR, 0.88; 95% CI, 0.54-1.43; P=.60). There were 24 deaths in the radiation group (4 related to Hodgkin’s lymphoma or effects from treatment and 20 related to another cause), while there were 12 deaths in the ABVD alone group (6 related to Hodgkin’s lymphoma or effects from treatment and 6 related to another cause). In the news conference, Dr. Meyer addressed the study’s main limitations: the radiation therapy used is now outdated, and the treatment in the control arm was “likely excessive” and possibly contributed to other cancers. He said that using subtotal nodal radiation therapy was the “central issue” of the trial. “While the risks we saw would likely be reduced with modern treatment [involved-field radiation therapy], we don’t know how much they would be reduced,” Dr. Meyer said. “This will be a source of debate.” However, Dr. Meyer added that he and the other authors were confident that ABVD alone was an appropriate treatment option in this subgroup of patients.