Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: Long-term results of a randomized trial of radiotherapy alone

Purpose: To show that radiotherapy (RT) dose to the noninvolved extended fi eld (EF) can be reduced without loss of efficacy in patients with early-sta ge Hodgkin's disease (HD). Patients and Methods: During 1988 to 1994, pathologically staged patients w ith stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sed imentation rate, or three or more involved areas) were recruited from vario us centers. All patients received 40 Gy total fractionated dose to the invo lved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF . No chemotherapy was given. RT films were prospectively reviewed for proto col violations and recurrences retrospectively related to the applied RT. Results: Of 382 recruited patients, 376 were eligible for randomized compar ison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 80 months, 7-year rela pse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). T he upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespirator y disease/pulmonary embolisms (seven), second malignancy (six), and HD (fiv e). Protocol violation was associated with significantly poorer RFS. Nonirr adiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. Conclusion: EF-RT alone attains good survival rates in favorable early-stag e HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rare. (C) 2001 by Ame rican Society of Clinical Oncology.