Early-Stage Hodgkin's Lymphoma: In Pursuit of Perfection

Abstract

It was estimated that 8,830 patients would be diagnosed with Hodgkin’s lymphoma (HL) in the United States in 2011, and that approximately half of those patients would have early-stage disease. The treatmentofearly-stageHLhasevolvedovertime,resultingincontinuous improvement in the cure rate and reductions in treatment-related toxicity. Today, combined modality programs are considered the standard of care for the majority of these patients, with an expected cure rate exceeding 80% and survival rate exceeding 90%. Despite these outstanding results, several groups continue to develop treatment programs in the hopes of achieving better curative and safety outcomes. To understand the results of key randomized studies in patients with early-stage HL, it is important to remember that the definition of early-stage disease varies widely among study groups and in different regions of the world. In North America, early stage is defined as stage I or II disease with no bulk or B symptoms. Patients with such disease are typically treated with four cycles of doxorubicin, bleomycin, dacarbazine, and vinblastine (ABVD) plus 30 Gy of involved field radiation therapy (IF-XRT). In contrast, patients with bulky disease ( 10 cm) are usually grouped with patients with advanced-stage disease and are treated with six to eight cycles of ABVD plus 36 Gy of IF-XRT, resulting in a 5-year failure-free survival of 85% and an overall survival of 95%. The definition of early stage that is used by the German Hodgkin’s Lymphoma Study Group (GHLSG) includes bulky stage I or II disease with no B symptoms. The GHLSG additionally classifies patients with early-stage disease into favorable (stage I/II disease with no risk factors such as bulk, elevated erythrocyte sedimentation rate, extranodal sites, or more than two involved lymph node regions) or unfavorable (stage I/II with any of these risk factors) categories. Patients with early-stage favorable HL have an excellent cure rate; therefore, investigations of new therapeutic programs focus on reducing treatment-related toxicity, whereas patients with early-stage unfavorable HL continue to be candidates for the evaluation of new regimens that are aimed at additionally improving the cure rate. Using this approach, the GHLSG reported that patients with early-stage favorable HL could be successfully treated with a reduced-intensity regimen of two cycles of ABVD chemotherapy plus 20 Gy of IF-XRT instead of the standard four cycles of ABVD plus 30 Gy of IF-XRT. Using such a strategy, they were able to maintain a high 91% rate of freedom from treatment failure. In the article that accompanies this editorial, the GHLSG reports the results of the HD14 study that was aimed at improving treatment outcomes of patients with early-stage unfavorable HL by intensifying