# Wilms Tumor: Flank and Whole Abdominal Radiation

## Introduction

Wilms tumor, also known as nephroblastoma, is the most common renal malignancy in children, typically presenting between the ages of three and four years. Over several decades, cooperative group trials conducted by the National Wilms Tumor Study Group (NWTSG) and the Children's Oncology Group (COG) have significantly improved outcomes, with cure rates now exceeding 90% for most clinical presentations. Radiation therapy remains a crucial component of treatment for selected stages and histologic subtypes of Wilms tumor, complementing surgical resection and chemotherapy.

## Staging and Risk Stratification

### NWTS/COG Staging System

The NWTS/COG staging system classifies Wilms tumor based on the extent of disease and surgical findings. Stage I tumors are confined to the kidney and are completely resected. Stage II tumors extend beyond the kidney but are also completely resected without residual disease. Stage III is characterized by residual nonhematogenous tumor, which may include positive surgical margins, lymph node involvement, peritoneal implants, or tumor spillage. Stage IV involves hematogenous metastases, commonly affecting the lungs, liver, bone, or brain. Finally, Stage V refers to bilateral disease present at diagnosis.

### Histologic Classification

Histologically, Wilms tumors are categorized based on the presence or absence of anaplasia. Favorable histology (FH), which lacks anaplasia, accounts for approximately 90% of cases. Focal anaplasia is limited to one or a few areas within the tumor, whereas diffuse anaplasia (DA) involves widespread anaplastic changes and is associated with poorer outcomes and TP53 mutations.

## Indications for Radiation Therapy

### Flank Radiation

Radiation therapy to the flank is indicated primarily for Stage III favorable histology tumors, which include cases with positive surgical margins, lymph node involvement, or tumor spillage confined to the flank region. For diffuse anaplasia, radiation is required for all Stage II and III cases regardless of complete resection status. In contrast, Stage I and II tumors with focal anaplasia generally do not require radiation if they have been completely resected.

### Whole Abdominal Radiation

Whole abdominal radiation is reserved for situations involving diffuse peritoneal contamination or seeding, such as pre-operative or intra-operative tumor rupture with spillage beyond the flank. It is also indicated when peritoneal implants are present at any site or when peritoneal cytology is positive for tumor cells.

### Whole Lung Irradiation

For Stage IV disease with pulmonary metastases that fail to achieve a complete response following chemotherapy, whole lung irradiation is administered. According to COG protocols, this is typically assessed by a CT scan at week six of treatment. The standard dose is 12 Gy delivered in 8 fractions of 1.5 Gy each. If lung metastases clear with chemotherapy alone, radiation may be omitted based on newer COG guidelines.

![Illustration of radiation field design for flank radiation and whole abdominal radiation in Wilms tumor](images/wilms-rt-fields.jpg)

## Flank Radiation Technique

### Target Volume

The target volume for flank radiation includes the tumor bed as defined by pre-operative imaging and operative findings. To prevent scoliosis caused by asymmetric irradiation of the vertebral growth plates, the entire width of the vertebral body must be included. This requires the medial border of the radiation field to cross the midline to encompass the full vertebral body. Superior and inferior borders extend beyond the pre-operative tumor margins to ensure adequate coverage.

### Dose and Fractionation

For Stage III favorable histology tumors, the standard dose is 10.8 Gy delivered in 6 fractions of 1.8 Gy each, as per protocol AREN0532. Areas of gross residual disease receive a boost of an additional 10.8 Gy, totaling 21.6 Gy. In cases of diffuse anaplasia, the dose is escalated to 19.8 Gy, with a boost to 30.6 Gy for gross residual disease.

| Indication | Field | Dose | Fractions | Boost |
|---|---|---|---|---|
| Stage III, favorable histology | Flank | 10.8 Gy | 6 x 1.8 Gy | +10.8 Gy for gross residual (total 21.6 Gy) |
| Stage II-III, diffuse anaplasia | Flank | 19.8 Gy | 11 x 1.8 Gy | +10.8 Gy for gross residual (total 30.6 Gy) |
| Peritoneal spillage / contamination (FH) | Whole abdomen | 10.5 Gy | 7 x 1.5 Gy | Tumor bed boost per flank guidelines |
| Peritoneal spillage (DA) | Whole abdomen | 19.8–21 Gy | Per protocol | Tumor bed boost |
| Pulmonary metastases (persistent) | Whole lung | 12 Gy | 8 x 1.5 Gy | — |
| Hepatic metastases | Whole liver | 19.8 Gy | 11 x 1.8 Gy | Boost to gross disease |

### Timing

Radiation therapy should commence within 14 days of nephrectomy, following COG guidelines. Delays beyond this window have been linked to increased risk of local recurrence. Radiation is administered concurrently with chemotherapy agents such as vincristine, dactinomycin, and sometimes doxorubicin.

## Whole Abdominal Radiation Technique

### Field Design

Whole abdominal radiation fields encompass the entire peritoneal cavity, extending from the diaphragm to the pelvic floor. The femoral heads are included initially to cover the inguinal portions of the peritoneum, but shielding of the femoral heads is applied after 12 Gy to minimize growth disturbances. The field design ensures adequate coverage of the hepatic and splenic flexures.

### Dose

For favorable histology tumors, the dose is typically 10.5 Gy delivered in 7 fractions of 1.5 Gy each. Diffuse anaplasia cases require higher doses, ranging from 19.8 to 21 Gy according to protocol. An additional boost to the tumor bed follows the guidelines established for flank radiation.

### Organ at Risk Considerations

Careful attention is given to protecting organs at risk during whole abdominal radiation. The remaining kidney must receive a dose below its tolerance threshold, generally less than 14.4 Gy in conventional fractionation. The whole liver dose should not exceed 19.8 Gy. Oophoropexy may be performed to facilitate ovarian shielding and reduce the risk of infertility. Symmetric irradiation of the full vertebral bodies is essential to prevent growth abnormalities.

![AP simulation image showing whole abdominal radiation field for Wilms tumor with kidney and liver shielding blocks](images/wilms-wai-field.jpg)

## Special Considerations

### Bilateral Wilms Tumor (Stage V)

In cases of bilateral Wilms tumor, nephron-sparing surgery is prioritized to preserve renal function. Pre-operative chemotherapy is used to reduce tumor volume before surgery. Radiation therapy decisions are based on the local stage of each kidney, with careful attention to limiting the dose to the remaining renal parenchyma.

### Hepatic Metastases

When hepatic metastases are present, whole liver irradiation is administered at a dose of 19.8 Gy in 11 fractions of 1.8 Gy each. This is given concurrently with flank or whole abdominal radiation when indicated. Boost doses to gross hepatic disease are delivered with careful consideration of dose constraints to minimize toxicity.

### Late Effects of Abdominal Radiation

Long-term complications of abdominal radiation include scoliosis and musculoskeletal asymmetry, which can be mitigated by symmetric irradiation of the vertebral bodies. Female patients are at risk for ovarian failure and infertility. Renal insufficiency may develop if the remaining kidney receives a significant radiation dose. Secondary malignancies such as soft tissue sarcoma and thyroid cancer can occur, particularly if radiation fields include the neck due to tumor spill. Additionally, patients may experience small bowel obstruction and chronic enteritis as late effects.

![Diagram showing long-term growth effects of asymmetric vs. symmetric vertebral body radiation in pediatric patients](images/wilms-vertebral-growth.jpg)

## COG Treatment Protocols

### AREN0532 (Stage III FH)

The AREN0532 protocol involves surgery followed by DD-4A chemotherapy, which includes vincristine, dactinomycin, and doxorubicin. Flank radiation of 10.8 Gy is initiated on day 9 post-nephrectomy.

### AREN0321 (Diffuse Anaplasia)

For diffuse anaplasia, the AREN0321 protocol prescribes intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, etoposide, and carboplatin. Radiation therapy is delivered to the flank at 19.8 Gy or to the whole abdomen as indicated, with additional boosts for residual disease.

## Key Clinical Pearls

Radiation therapy is indicated for Stage III favorable histology Wilms tumor and for all stages of diffuse anaplasia. Flank radiation should begin within 14 days of nephrectomy, as delays increase the risk of local recurrence. It is essential to include the full width of the vertebral body in the radiation field to prevent scoliosis caused by asymmetric growth plate irradiation. Whole abdominal radiation is reserved for cases with diffuse peritoneal contamination or tumor rupture with spillage beyond the flank. Whole lung irradiation at 12 Gy is used for pulmonary metastases that do not clear following initial chemotherapy.

## References

1. D'Angio GJ, Breslow N, Beckwith JB, et al. Treatment of Wilms' tumor: results of the Third National Wilms' Tumor Study. *Cancer*. 1989;64(2):349-360.  
2. Kalapurakal JA, Dome JS, Perlman EJ, et al. Management of Wilms' tumour: current practice and future goals. *Lancet Oncol*. 2004;5(1):37-46.  
3. Ehrlich PF, Ferrer FA, Ritchey ML, et al. Hepatic metastasis at diagnosis in patients with Wilms tumor is not an independent adverse prognostic factor for stage IV Wilms tumor: a report from the Children's Oncology Group/National Wilms Tumor Study Group. *Ann Surg*. 2009;250(4):642-648.  
4. Kalapurakal JA, Li SM, Breslow NE, et al. Intraoperative spillage of favorable histology Wilms tumor cells: influence of irradiation and chemotherapy regimens on abdominal recurrence. A report from the National Wilms Tumor Study Group. *Int J Radiat Oncol Biol Phys*. 2010;76(1):201-206.