For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of
Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral
tumors of standard histology and free of
metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less
ruptures, lower stage) of preoperative radiation and
actinomycin D (AMD) in SIOP-2, with all children having
radiation therapy either preoperatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative
radiation therapy and AMD were compared with preoperative
chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative
radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having
radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined.