INFLUENCE OF MORE EXTENSIVE RADIOTHERAPY AND ADJUVANT CHEMOTHERAPY ONLONG-TERM OUTCOME OF EARLY-STAGE HODGKINS-DISEASE - A METAANALYSIS OF23 RANDOMIZED TRIALS INVOLVING 3,888 PATIENTS

Purpose: To assess the effect of more extensive radiotherapy and of ad juvant combination chemotherapy on long-term outcome of early-stage Ho dgkin's disease.Methods: In a collaborative worldwide systematic overv iew, individual patient data were centrally reviewed on 1,974 patients in eight randomized trials of more versus less extensive radiotherapy and on 1,688 patients in 13 trials of radiotherapy plus chemotherapy versus radiotherapy alone. Crude mortality data on 226 patients in two other trials of chemotherapy were also reviewed. Results: More extens ive radiotherapy reduced the risk of treatment failure (resistant or r ecurrent disease) at 10 years by more than one third (31.3% v 43.4% fa ilures; P < .00001), but there was no apparent improvement in overall 10-year survival (77.1% v 77.0% alive). The addition of chemotherapy t o radiotherapy halved the 10-year risk of failure (15.8% v 32.7%; P < .00001), with a small, nonsignificant improvement in survival (79.4% v 76.5% alive). This involved a reduction of borderline significance fo r deaths from Hodgkin's disease (12.3% v 15.4% dead at 10 years; P = . 07), which was partly counterbalanced by a nonsignificant excess of de aths from other causes (12.4% v 10.0% 10-year risk).Conclusion: More e xtensive radiotherapy fields or the addition of chemotherapy to radiot herapy in the initial treatment of early-stage Hodgkin's disease had a large effect on disease control, but only a small effect on overall s urvival. Recurrences could be prevented by more extensive radiotherapy or by additional chemotherapy. However, if chemotherapy had not been given initially, recurrences were generally salvageable by re-treatmen t with chemotherapy. Hence, less intensive primary treatment-particula rly a reduction in radiotherapy fields-appears to achieve similar surv ival rates as more intensive treatment, although more randomized evide nce is needed to confirm this. (C) 1998 by American Society of Clinica l Oncology.