This document provides information on Wilms tumor (nephroblastoma), the most common malignant renal tumor of childhood. It discusses the epidemiology, genetics, clinical features, staging, histology, management including surgery, chemotherapy and radiation therapy. Key points include that Wilms tumor arises from nephrogenic rests, affects children aged 3-4 years, and is highly curable with multimodality treatment depending on stage, histology and other risk factors. Radiation therapy is an important component of treatment for local and metastatic disease. Ongoing clinical trials continue to refine risk-adapted therapies to improve survival while reducing long-term effects.

2. Introduction
 Also known as Nephroblastoma
 Most common primary malignant renal tumor of
childhood
 2nd most common malignant abdominal tumor in
childhood
Perez and Brady’s Principles and Practice of Radiation Oncology (sixth edition)

3. EPIDEMIOLOGY
 6% of pediatric malignancies
 More than 95% of kidney tumors in children
 Incidence : 8 cases per 1 million children (<15 years)
 Mean age : 3-4 yr of age
 Bilateral WTs : 7%
 Multifocal in single kidney : 12%
Perez and Brady’s Principles and Practice of Radiation Oncology (sixth edition)

4. Genetics and molecular biology
 Chromosome 11p13 (WT-1 gene):
 WAGR syndrome (gene deletions)
 Denys Drash Syndrome (point mutations)
 Chromosome 11q15(WT- 2 gene):
 Beckwith -Wiedemann Syndrome (gene deletions)
 Loss of heterozygosity (LOH) at 16q and 1p
 Wilms tumor suppressor gene on the X chromosome, WTX
Perez and Brady’s Principles and Practice of Radiation Oncology (sixth edition)

5. WAGR Syndrome
Wilms Tumor
Aniridia
Genitourinary abnormalities
Mental
Retardation

6. Denys Drash Syndrome
Diffuse Mesangial
Sclerosis
Male
PseudohermaphorditismWilms Tumor

7. Beckwith-Wiedemann Syndrome
Microcephaly
Umbilical Hernia
Ear lobe crease Macroglossia
Hemihypertrophy

8. Gross pathology
 Large tumor compressing
the normal renal
parenchyma
 Intact fibrous capsule with
prominent veins
 Yellowish color with
heterogeneous appearance
– hemorrhagic/cystic areas.

10. Anaplasia
 3 cytological abnormalities:
o Hyperdiploid mitotic figures
o Nuclear enlargement (3x or more)
o Hyperchromasia
 Diffuse or Focal : even in one or two foci is enough to impart a
markedly worse prognosis
 These changes are associated with high rates of relapse and
death

11. Nephrogenic Rests
 Foci of abnormally persistent embryonal tissue
 Present in up to 36% of kidneys which develop
unilateral WT and almost 100% of kidneys
involved by bilateral WT.
 Intralobar nephrogenic rests
 Perilobar nephrogenic rests

12. Clinical Features
● Abdominal lump (60-70%) : smooth, firm, non
tender mass on one side of abdomen
● Other symptoms:
– Hematuria (25%)
– Hypertension
– Fever

13. Pretreatment Work Up (COG)
 History : Record pre-existing conditions, family history of
cancer, or congenital defects
 Physical examination :Blood pressure, weight, height, presence
of abdominal masses, congenital anomalies particularly
genitourinary, hemihypertrophy, and aniridia
 Laboratory : Hemoglobin, white cell and differential counts,
platelets, urinalysis, serum blood urea nitrogen, creatinine,
protein and aspartate aminotransferases, alkaline
phosphatase, bilirubin

14. Pretreatment Work Up
 Radiology : CT or MRI scan of the abdomen and pelvis,
abdominal ultrasonography, chest CT scan, chest x-ray
 Bone scan and MRI of the brain (CCSK , RTK, and renal cell
carcinoma)

15. Physical Examination

19. MRI

20. Comparison of diagnostic performance of CT and MRI
for abdominal staging of pediatric renal tumors: a
report from the Children's Oncology Group
 Servaes et al
 Feb 2015
 CT and MRI have similar diagnostic performance for detection
of lymph node metastasis and capsular penetration. MR
detected more contralateral synchronous lesions; however
these were present in a very small number of cases. Either
modality can be used for initial loco–regional staging of
pediatric renal tumors.

21. Children’s Oncology Group Staging of Wilms’Tumor ,
Rhabdoid Tumor and Clear Cell Sarcoma of the Kidney
 Stage I: Tumor limited to kidney, completely resected.
The renal capsule is intact.
 The tumor was not ruptured or biopsied prior to
removal.
 The vessels of the renal sinus are not involved.
 There is no evidence of tumor at or beyond the
margins of resection.

22. Stage II:
The tumor is completely resected and there is no evidence of
tumor at or beyond the margins of resection.
The tumor extends beyond kidney, as is evidenced by any one
of the following criteria:
 There is regional extension of the tumor (i.e., penetration of
the renal capsule or extensive invasion of the soft tissue of the
renal sinus)
 Blood vessels within the nephrectomy specimen outside the
renal parenchyma, including those of the renal sinus, contain
tumor.

23. Stage III:
Residual non hematogenous tumor present following surgery and confined to
abdomen. Any one of the following may occur:
 Lymph nodes within the abdomen or pelvis are involved by tumor.
 The tumor has penetrated through the peritoneal surface
 Gross or microscopic tumor remains postoperatively
 The tumor is not completely resectable because of local infiltration into
vital structures
 Tumor spillage occurring either before or during surgery
 The tumor was biopsied before removal

24.  Stage IV :Haematogenous metastases (i.e., lung, liver,
bone, brain) or lymph node metastases outside the
abdomino pelvic region
 Stage V: Bilateral renal involvement by tumor is
present at diagnosis.

25. Multimodality Management
● Wilms Tumors are highly chemo and radiosensitive
● Tumor stage and histology are the main prognostic indicators that
determine the treatment regimen
● Surgery and chemotherapy comprise the main therapy for Wilms
tumors, with the addition of radiation for metastatic or histologically
aggressive tumors.

26. Surgery
● Primary method for achieving local control
● Transverse transabdominal, transperitoneal incision
● The standard procedure includes:
– Unilateral radical nephrectomy
– Selective sampling of nodes : para-aortic, celiac, and iliac areas
– Renal vein and IVC should be palpated to exclude intravascular tumor
extension
– Routine exploration of the contralateral kidney is not necessary if
imaging is satisfactory and does not suggest a bilateral process.
● The use of titanium clips to identify residual tumor and margins of
resection is also recommended

27. Role of nephron-sparing surgery
– Indicated in bilateral Wilms tumor
– WT in patients with genetic predisposition
– WT in solitary functional kidney / renal failure
– Very young infants < 6 months age
DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology
10th edition

28. Neoadjuvant Chemotherapy
● Solitary kidney
● Bilateral renal tumors
● Tumor in a horseshoe kidney
● Tumor thrombus in the inferior vena cava above the
level of the hepatic veins
● Respiratory distress as a result of extensive metastatic
disease
DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology 10th edition

29. Stage I
 Overall Survival : 92 -95%
 Patients in this stage group can be spared radiation
therapy and given adjuvant chemotherapy
 EE4A regimen -18 week course of Vincristine &
Actinomycin D
 Rhabdoid tumors - RTK regimen ( Carboplatin,
Etoposide, Cyclophosphamide, MESNA with GCSF
support)

30. Stage II
 Overall Survival : 89-92%
 FH & FA : EE4A regimen and radiation can be avoided.
 UH : Regimen I (Vincristine, Doxorubicin,
Cyclophosphamide, MESNA, Etoposide)
 Radiation therapy : DA, CCSK, RTK
 Patients with Rhabdoid histology are treated with
Regimen RTK

31. Stage III
 Overall Survival : 70 – 88%
 DD4A regimen : Dactinomycin, Vincristine,
Doxorubicin over 24 weeks
 All patients irrespective of histology should receive
flank radiation in this stage (Dose recommended is
10.8 Gy in 1.8 Gy per fraction with optional boost of
10.5 Gy)

32. Stage IV
 Primary surgery even in the setting of metastatic disease if the disease is
operable with the provision that chemotherapy is started at week 0.
 Alternative approach is to go for neoadjuvant chemotherapy
 In patients with FH/ FA the DD4A regimen is used while the regimen I is
used in presence of CSSK / DA.
 In patients with RTK – RTK regimen is used.
 Radiation therapy is to be delivered as per the local stage but a minimum
dose of 10.8 Gy to the flank is given.
 RT is also indicated in other metastatic sites

33. Bilateral Wilms Tumor
● Account for 7% of all WT
● Both sides staged separately
● Metachronous tumors are worse than synchronous
● Overall survival rates 78%.
Initial open biopsy / Trucut
biopsy and staging
Downstaging with
Chemotherapy
Bench Surgery
Partial nephrectomy
NWTS-3 , NWTS -4

34. Radiation Timing
● Important information from the NWTS 3 / 4 trial
● Showed that radiation therapy delay by more than
10 days may result in increased risk of recurrence.
● NWTS 1 showed that if RT was initiated after 10 days
there was a 10% risk of local relapse especially in
patients with UFH

35. Flank Radiation
● Parallel opposed field
● Supine
● Planning target volume : Tumor bed (outline of the kidney and
associated tumor on the initial CT or MRI) with a 1-cm margin
● The medial border must cross the midline to include the entire
width of the vertebrae
● Beam energy: 4-6 MV
● Dose : 10.8 Gy in 1.8 Gy per fraction over 6 fractions.

36. Flank Radiation: Manual
● Superior border: 1 cm above the line between
the lower border of body of sternum and
transpyloric plane
● Inferior border: Kept along a line passing
through the transtubercular plane
● Medial border: Kept 1.5 - 2 cm across the
midline to encompass the vertebral bodies
● Lateral border: Kept open

37. Flank radiation
● Anteroposterior flank irradiation
portal showing inclusion of the
entire width of the vertebral body in
the irradiated volume.
● The outline of the right kidney (RK)
and the WT from the preoperative
computed tomography scan is
shown

38. Whole Abdomen Radiation
● Indications:
– Peritoneal implants
– Tumor spillage during surgery
– Preoperative tumor rupture
● Dose prescribed is 10.8 Gy in 1.5 Gy / # - this can be
followed by a selected boost of 10.5 Gy to the Tumor
bed.
● Energy : 4-6 MV photons

39. WAR Manual Marking
● Superior border:
– At the upper border of the
nipples
● Inferior border:
– Superior border of the
symphysis pubis
● Shielding of acetabulum and
femoral heads

40. WAR: Simulator markings
● Superior border:
– Extend to the level of dome of
diaphragm
● Inferior border:
– To the level of inferior border of the
obturator foramen.
● Lateral border:
– Extends to the lateral peritoneal
reflection
● Acetabular head and the femoral head
shielded to prevent slipped femoral
epiphyses

41. Lung Bath: Manual
● Superior border:
– 3cm above the clavicle
● Inferior border:
– Below the xiphisternum
● Lateral borders:
– Lateral border of nipples

42. Lung bath: Simulator marking
● Superior border:
– Extends above the superior
border of the lateral edge of
clavicle
● Inferior border:
– Below extends to level of L1
(transpyloric plane)
– Field border is kept 1 cm
below the costophrenic
angles
● Shielding for humeral head
necessary.

43. Other recommended doses
● Lung Mets : 12Gy WLI in 8#
● Brain Mets : 30.6 Gy whole brain in 17 fractions Or 21.6
Gy to whole brain followed by 10.8Gy IMRT/ stereotactic
boost
● Liver mets : 19.8Gy whole liver in 11#
● Bone Mets :25.2 Gy to the lesion plus 3-cm margin
● Unresected Nodal Mets : 19.8 Gy
Children’s Oncology Group Renal Tumor Protocol Radiation Therapy Gui delines

44. Relapsed / Refractory WT
● The most frequent site of relapse overall is the lungs
● Good prognosis in relapse:
– Tumors with favourable histology
– Recurred only in the lungs
– Relapse in the abdomen where radiotherapy had not been
included in the primary treatment
– Relapse that occurred more than 12 months from diagnosis.

45. RT for Recurrent Abdominal
Tumors
● 12.6–18 Gy (<12 months)
● 21.6 Gy (older children, previous RT ≤10.8
Gy)
● Boost dose of 9 Gy to gross residual tumor
Children’s Oncology Group Renal Tumor Protocol Radiation Therapy Gui delines

46. First National Wilms Tumor Study
(1969–1974)
 Postoperative RT was not necessary for children younger than
2 years of age with group I tumors
 Combined dactinomycin and vincristine for irradiated patients
with group II and III tumors was better than therapy with
either agent alone.
 The RFS with and without RT among patients with group I
tumors younger than 2 years of age was 90% and 88%,
respectively

47. Second National Wilms Tumor Study
(1974–1979)
 In patients with group I tumors there was no survival
difference between 6 months or 15 months of dactinomycin
plus vincristine.
 Patients with groups II to IV tumors had a superior 2-year RFS
of 77% with doxorubicin, dactinomycin, and vincristine
compared with 63% with dactinomycin and vincristine alone.

48. Third National Wilms Tumor Study
(1979–1985)
 RT and doxorubicin could be eliminated in children with
stage II FH tumors.
 Patients with stage III FH tumors who received
doxorubicin or 20 Gy had fewer abdominal relapses than
those receiving 10 Gy without doxorubicin
 The addition of cyclophosphamide in high-risk patients
did not improve outcomes

49. Fourth National Wilms Tumor
Study (1986–1994)
 The results proved that the survival was similar
among patients who received standard-course (5
days) or single-dose, pulse-intensive dactinomycin
chemotherapy.
 Further, pulse intensive therapy was associated with
less hematologic toxicity and marked reduction of
treatment costs.

50. Fifth National Wilms Tumor Study
(1995–2001)
 It was a non randomized study to evaluate the prognostic
factors involved in WT
 LOH at Chr 1p and 16q were significant in determining an
adverse prognosis.

51. Differential Diagnosis of Lump
Abdomen in a child
 Benign
 Hydronephrosis
 Polycystic disease
 Splenomegaly (left
sided tumors)
 Malignant
 Neuroblastoma
 NHL
 Rhabdomyosarcoma
 Germ Cell Tumor
 Hepatoblastoma

52. Thank You