Abdominal irradiation in unilateral nephroblastoma and its impact on local control and survival

The influence of abdominal radiotherapy was analyzed in 122 patients with unilateral Wilms tumor eligible for local irradiation according to postoperative SIOP-stage.

122 of 454 children with Wilms tumor diagnosed between January 1989 and March 1994 in Germany were eligible for abdominal irradiation after preoperative chemotherapy and tumor resection according to SIOP9/GPOH protocol. There were 88 children with standard histology (SH; local Stage IIN+ and III) and 34 children with unfavorable histology (UH; anaplastic, clear cell and rhabdoid, local Stages II and III). Local irradiation was given postoperatively parallel to polychemotherapy according to protocol with appropriate dose reductions of Actinomycin D (dactinomycin) during the course of radiotherapy. Fifteen Gy to the tumor bed were prescribed in standard histology, with 30 Gy to regional lymph nodes, if histologically positive. Thirty Gy were given in unfavorable histology. Boost doses up to 15 Gy were possible for macroscopic residuals. Ages ranged between 6 months and 21 years (median 4.2 years).

Only 98 of 122 eligible children were irradiated. Reasons for ommission of radiotherapy were: Stage III only due to intraoperative biopsy (n = 6), due to resected cava thrombus (n = 5); young age (n = 2); undergrading/understaging (n = 7); other reasons (n = 4). There were 19 abdominal recurrences (4 of 88 with SH; 15 of 34 UH). In 5 patients, local recurrence was the only site of failure. There were 6 local failures in 24 nonirradiated but eligible children (25%) vs. 13 of 98 in irradiated children (13%); p = 0.15. In SH 0 of 15 nonirradiated vs. 4 of 73 treated children (p = NS) and in UH 6 of 8 nonirradiated vs. 9 of 26 irradiated children developed local recurrence (p < 0.05). Of 19 children with local recurrence as one site of failure, 18 have died. This comprises 67% of 27/122 children with fatal outcome in the observation period. In the patients eligible for abdominal radiotherapy, projected 3-year relapse-free survival is 85% for the group of children with standard histology and 41% for the children with unfavorable histology.

Despite impressive overall results for this multicenter trial in unilateral nephroblastoma, local recurrence remains a grave prognostic parameter. Evaluation of irradiated vs. eligible but not irradiated children suggests that radiotherapy to the tumor bed is of considerable impact for local control in the risk groups eligible for abdominal irradiation as defined in the SIOP9/GPOH protocol.