Controversies in Early-Stage Hodgkin’s Disease

The optimal choice of treatment for early-stage Hodgkin’s disease depends on (1) knowledge of the prognostic factors that may influence treatment outcome and (2) the risk of acute and long-term complications incurred by treatment. For prognostic and therapeutic considerations, patients are divided into those with early-stage, favorable-prognosis disease (clinical stage I/II without risk factors) and those with early-stage, unfavorable-prognosis or intermediate-stage disease (clinical stage I/II with risk factors).

Based on the results of earlier trials, the European Organization for Research and Treatment of Cancer (EORTC) has defined clinical stage I/II (supradiaphragmatic only) patients as having favorable-prognosis, early-stage disease if none of the following risk factors are present: age > 50 years, asymptomatic disease with an erythrocyte sedimentation rate > 50 mm/h, B symptoms with an erythrocyte sedimentation rate > 30 mm/h, and a large mediastinal mass. In previous trials, stage II disease, mantle-cell or lymphocyte-predominant histology, and multiple involved regions had also been considered adverse factors.[1]

Since 1988, the German Hodgkin’s Lymphoma Study Group (GHSG) has defined clinical stage I/II patients as having favorable-prognosis, early-stage disease in the absence of the following adverse factors: large mediastinal mass, multiple involved regions, elevated erythorcyte sedimentation rate, localized extranodal infiltration (so-called E lesions), and massive splenic involvement.[2]

The Revised European-American Lymphoid (REAL) and World Health Organization (WHO) classifications of Hodgkin’s disease contained one important modification of the Rye system—the definition of the lymphocyte-predominant (paragranuloma) subtype. Most patients with the lymphocyte-predominant subtype present with early-stage disease and enjoy an excellent prognosis despite a propensity for local relapse. Current treatment strategies favor limited radiation therapy for these patients.[3]

Early-StageDisease With Favorable Prognosis

Extended-field radiotherapy alone produces a complete remission in 90% to 98% of patients with early-stage favorable-prognosis Hodgkin’s disease.[4] Although 30% to 40% will relapse, salvage chemotherapy or combined-modality therapy will yield new remissions in most cases. Approximately 75% to 85% of patients with early-stage favorable-prognosis disease who receive extended-field radiotherapy as first-line therapy are alive after 10 years.

Increasing concern about the long-term consequences of treatment prompted many investigators in the 1970s and 1980s to reexamine the aggressive approaches developed for the staging and treatment of early-stage favorable-prognosis disease. In several follow-up studies, an increased risk of secondary cancer was reported for surviving patients.