The EORTC treatment of early stages of Hodgkin's disease: the role of radiotherapy

Since 1964, the European Organisation for Research and Treatment of Cancer has conducted three subsequent clinical trials on clinical Stages (CS) I + II Hodgkin's disease (HD) in which 1059 patients have been entered. The first trial compared regional radiotherapy (RT) with mantle field or inverted Y, versus the same RT followed by a weekly injection of vinblastine for 2 years. The relapse free survival (RFS) and overall survival (S) were higher in patients treated by RT and chemotherapy (CT). This benefit, however, was significant only in patients with a mixed cellularity histologic type. The second trial compared the therapeutic efficacy of splenic irradiation versus splenectomy and found that in both arms, RFS and S were identical. Moreover, it was found that splenic involvement was correlated with an increased incidence of relapse in extranodal sites and in non irradiated lymphatic areas. In this trial, CT was given only to patients with poor histologic types, mixed cellularity or lymphocytic depletion. In the third trial, staging laparotomy was performed only to further delineate a good prognostic group which could be treated by RT alone. In this limited treatment group, there was no difference in RFS and S between mantle field and mantle field + para-aortic RT. In the extensive treatment group, total nodal irradiation (TNI) was compared with RT + MOPP. The RFS was slightly lower in the TNI arm, but there was no significant difference in S. The data of the 3 trials underline the importance of prognostic factors in the choice of optimal treatment and show that their significance depends upon the type of treatment. Multivariate statistical analyses showed that the main prognostic factors, which can help to identify the subsets of patients who can be treated by RT alone, are (1) systemic symptoms and elevated erythrocyte sedimentation rate (ESR), (2) the number of involved lymphatic areas, and (3) staging laparotomy. Extended RT (mantle + para-aortic + spleen treatment) gives satisfactory results in patients without systemic symptoms and/or elevated ESR and one or two involved sites, whereas TNI or combined modality treatment becomes mandatory for patients with 3 or more involved sites or splenic involvement and/or systemic symptoms. With proper adjustment of the irradiated volume, a very large proportion of CS I + II patients can be best treated by RT alone.