When are increased flank doses beneficial in Stage III Wilms tumor?

The current standard of care in North America for radiotherapy dose in the treatment of Wilms tumor (WT) has been established by the National Wilms Tumor Study (NWTS)-3. This study randomized Stage III favorable histology patients to 1000 cGy vs. 2000 cGy as well as 2 drugs (actinomycin D and vincristine) vs. 3 drugs (actinomycin D, vincristine, and doxorubicin) and found that radiotherapy dose can be lowered to 1000 cGy in conjunction with 3 drugs. (Thomas et al.)

For focal anaplastic and diffuse anaplastic Wilms tumor, a dose of 1080 cGy in 6 fractions was utilized in NWTS-5. However, in the Children’s Oncology Group AREN0321 study, a dose of 1980 cGy in 11 fractions was given to Stage III diffuse anaplastic Wilms tumor. The local failure rate was 6.4% in COG AREN0321, compared to 14.8% seen in NWTS-5. (Daw et al). Currently, patients with diffuse anaplastic Wilms tumor receive 19.8 Gy instead of 10.8 Gy to the flank.

References:

Thomas et al., PMID 1655223

Daw et al., PMID 32134700

I believe this dose was determined by the AREN0321 protocol.

Typical indications for increased flank doses to 19.8 Gy in 11 fx include:

• Patients if ≥16 years of age
• Stage III tumors with diffuse anaplasia
• Stage I-III Rhabdoid tumor of the kidney if age > 1-year-old.

Note that a 10.8 Gy boost is added to any gross residual disease following surgery, for a total of 30.6 Gy.