The COG research study for very high risk renal tumors was AREN0321. The standard of care adopted by most institutions in North America would be to treat children with very high risk renal tumors according to this studies' protocol guidelines until another study is available
The pathology types below make up a very small proportion of renal tumors in children, but account for most deaths.
Very high risk renal tumors eligible for AREN0321:
Pathology |
Proportion of all Renal Tumors |
Anaplastic Wilms tumor |
7.5% |
3.5% |
|
Malignant rhabdoid tumor (MRT) |
1.6% |
Renal cell carcinoma (RCC) |
5.9% |
Anaplastic Wilms Tumor
-
Anaplastic histology is the single most important histologic predictor of response and survival in patients with Wilms tumor.
-
Focal anaplasia does not confer as poor a prognosis as does diffuse anaplasia.
-
Stage I diffuse anaplastic histology did not do well in NWTS-5 and so their treatment is intensified (see table below).
-
NWTS-3 and NWTS-4 treated diffuse anaplastic Wilms tumor patients with 15 months of vincristine, actinomycin D, and doxorubicin. Also patients were randomized to receive additional cyclophosphamide.
-
Patients with Stages II-IV diffuse anaplastic histology had a 4-year relapse-free survival (RFS) of about 27% if they did NOT get cyclophosphamide vs 55% with addition of cyclophosphamide.
- NWTS-5 included cyclophosphamide into treatment protocol for these patients.
-
Most of these tumors have TP53 mutations.
- TP53 mutations are very uncommon in favorable histology.
- Microdissection analysis of tumors showed that TP53 mutations are restricted to areas of anaplasia.
- p53 induces cell cycle arrest or apoptosis in response to DNA damage - so inactivation of p53 may promote resistance to anti-cancer therapy.
Chemotherapy Treatment Regimes:
| Tumor and Stage | Treatment Regimen |
Focal anaplastic WT
Diffuse anaplastic WT
|
Regimen DD-4A
(vincristine/dactinomycin/doxorubicin x 25 weeks + Flank RT)
|
Focal anaplastic WT
Diffuse anaplastic WT
Diffuse anaplastic WT
|
Regimen UH1
(cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphamide; x 30 weeks + RT) |
|
Regimen I (vincristine/doxorubicin/cyclophosphamide; cyclophosphamide/etoposide x25 weeks; RT)
|
|
Surgery only |
Renal Cell Carcinoma
|
Institutional Preference |
Diffuse anaplastic WT
Malignant Rhabdoid Tumor
|
Window Therapy# IRINOTECAN/VCR (1 cycle) EVALUATION |
Indications for Flank or whole abdominal RT:
| Wilms Tumor: Focal Anaplasia | Abdominal stage I, II, III |
Wilms Tumor: Diffuse Anaplasia |
Abdominal stage I, II, III |
| Clear Cell Sarcoma | Abdominal stage II, III Stage I only if node sampling and / or pathology review not done |
| Rhabdoid Tumor | Abdominal stage I, II, III |
Site |
Indications & RT Dose |
Flank RT |
|
Whole Abdomen RT |
Stage III with:
Doses used as above for flank RT but at 150 cGy per fraction.
When dose to whole abdomen is more than 10.5 Gy (diffuse anaplasia or MRT), renal shielding limits dose to the normal kidney to less than 14.4 Gy
|
Whole Lung RT |
|
Lymph Node RT |
|
Liver RT |
|
| Bone RT |
|
A boost of 10.8 Gy is given to residual tumor after surgery
External links:
- Clear cell sarcoma at the Atlas of Genetics and Cytogenetics in Oncology and Haematology
- Clear cell sarcoma at the NCI
- Malignant rhabdoid tumor at the Atlas of Genetics and Cytogenetics in Oncology and Haematology
- Malignant rhabdoid tumor at the NCI
- Renal cell carcinoma at the NCI
