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Journal of Clinical Oncology, Vol 23, No 34 (December 1), 2005: pp. 8914-8915 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.03.9644
Radiotherapy and Hodgkin's LymphomaDepartment of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX To the Editor: We read with interest the article by Meyer et al and the accompanying editorial by Dr Canellos in the July 20, 2005, issue of the Journal of Clinical Oncology regarding the National Cancer Institute of Canada (NCI-C) trial.1,2 In this trial, patients with stage I to IIA Hodgkin's lymphoma were randomly assigned to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or subtotal nodal radiation. Patients with unfavorable risk disease in the radiotherapy arm also received ABVD. While there was no difference in overall or event-free survival between the two arms, freedom from disease progression was significantly higher in the radiotherapy arm, compared to the chemotherapy alone arm (93% v 87%, P = .006). The NCI-C trial has been the only trial designed to compare survival in adult patients treated with ABVD alone and those treated with radiotherapy, with or without ABVD. However, other recent studies have also investigated the role of radiotherapy in early-stage Hodgkin's lymphoma. As noted in the editorial, a randomized trial from India showed that in patients achieving a complete remission after 6 cycles of ABVD, the addition of radiotherapy significantly improved the 8-year event-free survival (88% v 76%, P = .01) and overall survival (100% v 89%, P = .002).3 The findings of this trial may not necessarily be applicable to all early-stage Hodgkin's lymphoma patients, since a large number of patients in this trial were under age 15, had stage III-IV lymphoma, or had mixed cellularity histology. The results from the recently presented European Organisation for Research and Treatment of Cancer GELA H9-F trial may be more pertinent.4 In the H9-F trial, patients with favorable, early stage Hodgkin's lymphoma with a complete remission after six cycles of epirubicin, bleomycin, vinblastine, and prednisone were randomly assigned to one of three arms: no radiotherapy, 20 Gy involved field, or 36 Gy involved field radiotherapy. The no radiotherapy arm of the trial had to be closed early since predefined stopping rules were met. The 4-year event-free survival was significantly lower in the no-radiotherapy arm (70%), compared to the 20 Gy (84%) and 36 Gy (87%) arms (P < .001). Of note, the epirubicin, bleomycin, vinblastine, and prednisone regimen in this trial may be associated with a higher rate of relapse than ABVD. A randomized trial from Memorial Sloan-Kettering Cancer Center failed to find any significant difference in overall survival or freedom from progression in patients treated with ABVD alone or ABVD followed by radiotherapy.5 However, this trial had closed early because of slow accrual and was not powered to detect any difference less than 20%. A randomized trial by the Children's Cancer Group (CCG) in the pediatric population has shown that the addition of involved field radiotherapy after complete response to chemotherapy improves event-free survival.6 Thus, results from four randomized trials (NCI-C, India, H9-F, and CCG) indicate that the addition of radiotherapy after chemotherapy improves either freedom from progression or event-free survival.1,3,4,6 These are important end points since patients who relapse require treatment with salvage chemotherapy, often including high-dose chemotherapy and autologous transplantation. In the NCI-C trial, patients in the radiotherapy arm had an increased number of second malignancies and cardiovascular events.1 However, the number of fatal second cancers or cardiovascular events was similar in the two arms (four with radiotherapy, three with ABVD alone). Moreover, the NCI-C trial used subtotal nodal irradiation at 35 Gy. The risk of second malignancies and cardiovascular events is likely to be much lower with the current standard of low-dose (20 to 30 Gy) involved field radiotherapy. Only long-term follow-up will reveal the true impact of low-dose involved field radiotherapy on survival.
The NCI-C trial excluded patients with bulky disease (>10 cm) or large mediastinal adenopathy ( Future studies should investigate which patient subgroups are most likely to benefit from involved field radiotherapy. Studies are also warranted to compare acute and long-term side effects, quality of life, and cost-effectiveness between chemotherapy alone (followed by salvage chemotherapy in some patients), and chemotherapy followed by involved field radiotherapy. We believe that low-dose involved field radiotherapy will continue to play an important role in the care of patients with early-stage Hodgkin's disease. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Meyer RM, Gospodarowicz MK, Connors JM, et al: Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol 23:4634-4642, 2005
2. Canellos GP: Chemotherapy alone for early Hodgkin's lymphoma: An emerging option. J Clin Oncol 23:4574-4576, 2005
3. Laskar S, Gupta T, Vimal S, et al: Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: Is there a need? J Clin Oncol 22:62-68, 2004 4. Noordijk EM, Thomas J, Ferme C, et al: First results of the EORTC-GELA H9 randomized trials: The H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin's lymphoma (HL). J Clin Oncol 23:561S, 2005
5. Straus DJ, Portlock CS, Qin J, et al: Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood 104:3483-3489, 2004
6. Nachman JB, Sposto R, Herzog P, et al: Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol 20:3765-3771, 2002 Related Reply
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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one-third chest diameter). The addition of radiotherapy to chemotherapy remains the standard of care for these patients. In patients that are at high risk of relapse, the improvement in event-free survival and freedom from progression from radiotherapy may lead to an overall survival benefit, despite an increased risk for second malignancies and cardiovascular events. 
