Wilms tumor carcinoma.

1. WIlMs TUMOR
GROUP C

2. Introduction to Wilms
Tumor
Wilms tumor, also known as nephroblastoma, is a type of kidney cancer
that primarily affects children. It is named after Dr. Max Wilms, the
German surgeon who first described it. This rare and complex disease
arises from immature kidney cells and is most commonly diagnosed in
children around the age of 3 to 4 years. Wilms tumor has a high rate of
cure, especially when it is detected and treated early. However, the
treatment requires a multidisciplinary approach involving surgery,
chemotherapy, and occasionally radiotherapy. The exact cause of Wilms
tumor is still unknown, although certain genetic and environmental factors
are believed to play a role.

3. EpidemiologyThe disease accounts for about 4% of all cancers in
children younger than 15 and is the most common kind of kidney
cancer in children.A Wilms tumor occurs most often in young
children, usually between the ages of 3 and 4. In fact, two-thirds of
Wilms tumors are diagnosed before age 5, and nearly all cases are
diagnosed before age 10. As children get older, these tumors are less
common, but they can still occur in people of any age. Wilms tumors
are slightly more common in girls than in boys, and the risk is slightly
higher in Black children than White children. Asian American children
have the lowest risk.

4. Histopathology and Risk Factors
Histopathology
Wilms tumor is characterized by the presence
of specific cell types and structures when
examined under a microscope. These include
blastema, stromal cells, and epithelial cells.
Understanding the histopathology is essential
for accurate diagnosis and treatment
planning.
Risk Factors
Although the exact cause of Wilms tumor is
unknown, certain risk factors have been
identified. These include genetic
predisposition, as the condition can
sometimes run in families. Additionally,
certain birth defects and syndromes are
associated with an increased risk of
developing Wilms tumor.

5. Risk factors
Genetic changes.
Children may have a mutated (changed), damaged, or missing gene. This change can also cause
other birth defects. About 15% of children with a Wilms tumor were born with other health
problems.
WAGR syndrome.
WAGR syndrome is a condition that causes a number of birth defects. Children with this syndrome
have a 33% chance of
developing a Wilms tumor. WAGR stands for:Wilms tumorAniridia (no iris in the eye)
Genitourinary abnormalities, which are changes to the reproductive and urinary organs, or
gonadoblastoma, which is a rare tumor of the reproductive organs Intellectual disabilityBeckwith-
Wiedemann syndrome. This condition causes enlarged internal organs and limbs.
Children with this syndrome have a higher risk of developing a Wilms tumor, kidney cysts, and
tumors of the liver (hepatoblastoma), pancreas, and adrenal glands.
Denys-Drash syndrome. This is a rare condition in which male genital organs do not develop correctly
and there is an increased risk of developing a Wilms tumor.Family history. A small number of children
with a Wilms tumor have a relative in their family with the disease.

6. Spread of Wilms Tumor
Local Spread
Wilms tumor can gradually spread beyond
the kidney to nearby tissues and organs in
the abdomen, such as the liver and lungs.
Distant Metastasis
In some cases, Wilms tumor can
metastasize to other parts of the body, such
as the bones and lymph nodes, leading to
more advanced disease.

7. Stages and Symptoms
Disease Stages
Wilms tumor is typically categorized into
stages I to V, based on the extent of cancer
spread and the involvement of nearby
structures. Staging helps determine the most
appropriate treatment approach.
Common Symptoms
The symptoms of Wilms tumor can vary, but
they often include abdominal pain or swelling,
blood in the urine, fever, and high blood
pressure. Early recognition of these
symptoms is crucial for timely intervention.

9. Diagnostic Methods
1 Imaging Studies
Diagnostic imaging techniques such
as ultrasound, CT scans, and MRI
are used to visualize the kidney and
surrounding structures to aid in the
diagnosis of Wilms tumor.
2 Biopsy
A biopsy involves the removal of a
small tissue sample from the kidney
for microscopic examination and
confirmation of the presence of
cancerous cells.
3 Genetic Testing
Genetic analysis can be performed to identify specific mutations or abnormalities that
may contribute to the development of Wilms tumor and to assess the risk of familial
recurrence.

10. Evaluation
The usual labs are not specific for Wilms tumor but need to be ordered to look for other
pathologies.
Routine blood work includes
Complete blood count to look for anemia
Chemistry profile
Renal function Urinalysis
Coagulation studies
Cytogenetic studies to look for 1p and 16q deletion.
Imaging studies utilized include the following:
Renal ultrasonography (often the initial study) but is operator dependent Chest x-ray to
look for lung metastases Abdominal and chest CT with sedation Abdominal MRI is an
optional study.

11. Stage I: The tumor is found in 1 kidney and can be completely removed with surgery.
Stage II: Cancer is found in the kidney and in the fat, soft tissue or blood vessels
near the kidney. It may have spread to the renal sinus. The renal sinus is the part of
the kidney where blood and fluid enter and exit the organ. The tumor can be
completely removed with surgery.
Stage III: Residual nonhematogenous tumor confined to the abdomen, or (a)
positivelymph nodes, (b) diffuse peritoneal contamination, (c) peritoneal
implants,(d) margins positive, (d) tumor spillage or ruptureA tumor that is biopsied
before surgery is stage III.
Stage IV: Cancer has spread to other, more distant organs, such as the lungs, liver,
bones, and brain, or to lymph nodes outside the abdomen. This is called metastasis.
Stage V: Cancer cells are in both kidneys at the same time. The tumor in each kidney
is staged separately.

12. Treatment Options for Wilms Tumor
1 Surgical Interventions
The primary treatment for Wilms tumor involves surgical removal of the affected
kidney and, if necessary, surrounding tissues. This is often the first step in
managing the disease.
2 Chemotherapy and Radiotherapy
Chemotherapy and radiation therapy are commonly used in Wilms tumor treatment
to destroy cancer cells that may remain after surgery and to minimize the risk of
relapse.

13. Combination chemotherapy is usually administered for more aggressive disease. Initial
chemotherapy most typically includes vincristine and dactinomycin. Doxorubicin,
cyclophosphamide, etoposide, and carboplatin are also used.[14]
Alkylating Agents: These drugs work by attaching alkyl groups to DNA strands, which
prevents the DNA from replicating properly. Examples include cyclophosphamide, cisplatin,
and carboplatin.
Mechanism of Action: Binding to DNA, causing DNA damage and interfering with DNA
repair mechanisms, ultimately leading to cell death.

15. Treatment Plans
Fractions
Chemotherapy and radiotherapy are often
administered in divided doses, known as
fractions, to optimize treatment effectiveness
while minimizing potential side effects.
Dose per Fraction
The dosage of each fraction is carefully
calculated and administered under the
supervision of experienced oncologists and
radiation specialists.

16. In general, EBRT is not indicated for stage I and II tumors, unless they are
unfavorable histologies.■ Regardless of histology, EBRT is indicated for stage III and
IV.
Localization, Immobilization, and simulation
■ Positioning: patient should be in supine position with arms above the head or
akimbo, especially if lung radiotherapy is necessary.
■ Localization: use operative reports and preoperative imaging to delineate
operative bed and/or residual disease.
■ Immobilization: a device such as a vac-loc bag aids in reproducing set-up.■
Simulation: A 4D or fluoroscopic simulation should be used to determine the
extent of motion of the targets and organs at risk, with particular atten-tion to the
lungs.

17. Dose/Fractionation
■ Radiotherapy to begin by postoperative day 9.■ Dose per fraction is 1.8 Gy, except
when large volumes are receiving EBRT in which case the dose is reduced to 1.5 Gy.
■ For patients 16 years or older, 30.6 Gy is prescribed for bone, lymph node, and brain
metastases; 19.8 Gy should be delivered to the flank or abdomen.
■ Any stage patient with clear cell sarcoma of the kidney should receive 10.8 Gy per
the stage III field indications (although stage I is controversial).
■ Any stage patient with rhabdoid tumor should receive 19.8 Gy per the stage III field
indications. Consider a lower dose for children younger than 1 year.
■ For stage V patients, preoperative chemotherapy is usually given. Each tumor should
be staged separately. Flank EBRT is recommended for patients with positive margins or
positive nodes to a dose of 10.8 Gy. Whole abdominal EBRT is required as per stage III
indications (

18. Gross disease should receive a boost of 10.8 Gy. For special con-siderations of small field
renal sparing radiotherapy, see the COG protocols.
■ Boost gross residual disease that is greater than 3 cm with an additional 10.8 Gy.
■ For diffuse anaplasia, a dose of 19.8 to 20 Gy should be used.
■ Irradiating lung metastases is controversial if diagnosed on chest CT, or in the setting of
favorable histology or complete response to chemotherapy.
■ Persistent focal lung disease 2 weeks after whole lung irradiation (WLI) should be excised
or receive a boost of 7.5 Gy in 5 fx.

19. Target Volumes and Treatment Planning
■ If WLI and flank or whole abdominal irradiation (WAI) are required, then the fields can be
treated simultaneously or sequentially.
If treating simul-taneously, the dose per fraction should be reduced to 1.5 Gy.
If treating sequentially, typically treat WLI first. In some cases, both the lung and
abdomen/flank can be treated with one field.
If the areas are treated with two separate fields, the match line should be feathered (moved
superiorly or inferiorly 0.5 cm every few fractions) to prevent excess liver and kidney dose
(Figure 12.1). See Table 12.2 for typical normal tissue constraints.

20. ■ Flank (AP/PA): the tumor and involved kidney as determined by the pre-operative CT scan
is the GTV.
A 1 to 2 cm margin should be added for the CTV; however, if the medial border extends to a
vertebral body then the CTV needs to include the entire body plus a margin of 1 cm (Figures
12.3 and 12.4).
■ WAI (AP/PA): the superior border is 1 cm above the diaphragm; inferior border is at the
bottom of the obturator foramen (with the femoral heads blocked) and the lateral borders
are 1 cm beyond the lateral abdominal walls. 3D conformal radiotherapy (3DCRT) or
intensity-modulated radia-tion therapy (IMRT) may be used to boost gross residual disease.
■ Whole brain: opposed laterals. For patients who receive a dose of 21.6 Gy and have three
or more lesions, a boost of 10.8 Gy may be given by IMRT or single-fraction stereotactic
radiosurgery (SRS).

22. Liver: for diffuse disease, the entire liver is the target. Otherwise, the lesions as seen on
imaging plus a 2 cm margin comprise the target.
Of note, if the lesion is solitary and resected with negative margins, radio-therapy is not
indicated.
■ Lymph nodes: the metastatic lymph nodes as determined by the pretreat-ment imaging
comprise the GTV. A 2 cm margin is added for the CTV.
■ Bone metastases: the bone lesion as seen on CT or MRI will determine the GTV and a 3
cm margin is added for the CTV.

25. Side Effects and Management
Short-term Effects
Short-term side effects of Wilms tumor
treatment may include nausea, hair
loss, fatigue, and increased
susceptibility to infections. These are
closely monitored and managed by the
medical team.
Long-term Effects
Long-term complications, such as risks
to kidney function and potential
secondary cancers, are important
considerations that are addressed
through ongoing follow-up care.

26. Prognosis and Follow-up Care
1 Prognosis
The outlook for Wilms tumor is
generally favorable, particularly
when it is diagnosed and treated at
an early stage. Regular follow-up
appointments and imaging tests are
essential to monitor long-term
outcomes.
2 Survivorship
Long-term survivorship care for
Wilms tumor patients focuses on
addressing potential late effects of
treatment, supporting overall well-
being, and promoting a healthy,
cancer-free future.