1. Nephroblastoma, also known as Wilms tumor, is the most common renal malignancy in children. It typically presents as an abdominal mass and can metastasize to lungs, liver, and bone. 2. Treatment involves nephrectomy followed by chemotherapy based on stage and histology. Radiation therapy may be given for local control in certain high risk cases. 3. With multimodal therapy, the cure rate for Wilms tumor is now over 90%. Ongoing surveillance is important due to risk of recurrence or secondary tumors.

1. Dr swarnita sahu
Dnb Radiation Oncology.
Batra hospital, New Delhi
(NEPHROBLASTOMA)

2. 3
Epidemiology
• Annual incidence in the USA is 7.6 per million(children <15 years.)
• Peak age – 3-4 years.
• Most common renal malignancy in children.
• higher in blacks, lower in Asians
• Male to female ratio is:
• 0.92:1.00 for U/L disease
• 0.60:1.00 for B/L disease
• Mean age of diagnosis :
• 46.9 months for females (29.5 mo for B/Ltumors)
• 41.5 months for males (32.6 mo for B/L tumors)

3. DEVELOPMENT OF KIDNEY

4. Development of wilms tumor

5. 7
Pathogenesis :
• Nephrogenic rests are the consequence
of residual metanephric tissue in a fully
developed kidney.
• Two types:
Intralobular (WAGR, Denys-Drash Syndrome etc)
Perilobular (Beckwith- Wiedemann Syndrome )

6. GROSS APPEARANCE

7. 11
Histology


8. 19
Signs and symptoms
• Classically-silent abdominal mass during
childhood (60-70%)
• Other signs and symptoms:
• Abdominal pain (30-40%).
• Hematuria (25%).
• Hypertension (25%).
• Varicocele (tumor thrombus in IVC).
• Associated GU abnormalities.
• Associated stigma of congenital
anomalies.

9. 21
Congenital Anomalies
●
Around 9 - 10% of individuals with Wilms tumour have a
congenital anomaly.
Long term F/U of individuals reveals a syndrome in 17%
patients.

10. 23
WAGR Syndrome (WT1 deletion ,11p13)
Wilms Tumor
Aniridia
Genitourinary abnormalities
Mental Retardation

11. 24
Denys Drash Syndrome (WT1 point mutation, 11p13)
Diffuse Mesangial Sclerosis
Male
PseudohermaphorditismWilms Tumor

12. 25
Beckwith-Wiedemann Syndrome (WT2 gene,11q15)
Microcephaly Ear lobe crease
omphalocoele
Macroglossia
Hemihypertrophy

13. OTHER SYNDROMES:
Simpson Golabi Behmel syndrome
Sotos Syndrome
Perlman Syndrome
Bloom syndrome
Alagille syndrome
Trisomy 18
Li-fraumani Syndrome
Children at risk should receive
abdominal screening USG every 3
months until 8 years.

14. Workup

15. 27
Investigations
◄ To establish the diagnosis
◄ Delineate tumor extent
◄ Confirm contralateral renal functional
status
◄ Discover any metastasis
◄ Assess fitness for surgery / anaesthesia
AIMS

16. PRE TREATMENT WORKUP
• HISTORY : pre existing conditions
family history
• EXAMINATION : general + systemic
• LAB : CBC, urinalysis, KFT, LFT.

17. RADIOLOGY :
USG ABDOMEN:
IOC for local disease
• organ of origin
• extent of spread
• patency of IVC
• detecting any involved lymph nodes.
TO ASSESS RENAL FUNCTION:
IVP
DMSA RENAL SCAN
CT-IVP
CT SCANS:
Extent and mets
Plain x rays:
Lung mets
CT BRAIN :
Rhabdoid tumor of kidney.
BONE SCAN :
Clear cell sarcoma

18. Large, heterogeneous mass lesion involving near entire right kidney with complex cystic and solid
component.

19. DIFFERENTIAL DIAGNOSIS
• Neuroblastoma
• Polycystic kidney
• Hydronephrosis
• Splenomegaly
• Rhabdoid tumor- associated brain mets
• RCC
• Clear cell carcinoma- associated skeletal mets
• Metanephric adenoma- nonspecific features
• Angiomyolipoma
• Lymphoma- associated lymphoma
Rhabdoid and clear
cell where
considered as
unfav histology of
wilms earlier BUT
NOW ARE
DISTINCT GROUPS

20. NATURAL HISTORY
• Often localized at the time of diagnosis.
(curative treatment i.e surgery followed by radiotherapy in 50 % of
the patients)
• Current cure rate >90%.
• Most common metastatic site : lungs
lymph nodes
liver

21. Histology: NWTSG(National Wilms Tumor Study Group )
• Absence of anaplasia (favorable histology):
• Presence of anaplasia (unfavorable histology):
•Focal anaplasia: anaplastic nuclear changes confined to restricted foci within the
primary tumor
•Diffuse anaplasia: involvement of any extrarenal site, renal sinus, extracapsular involvement,
sinus, nodal, and distant metastases, or extreme nuclear pleomorphism in one area or
involvement of multiple areas within one slide.

22. Staging (Children Oncology Group-successor of NWTS )
SIOP Staging- staging after preop
chemo

23. 35
Stage I
Tumor confined to the kidney
Completely excised
Capsule intact
Note : tx not ruptured/ biopsied prior sx
Vessels – not involved
Margins of resection – free

24. 36
Stage II
Tumor extends beyond the kidney evidenced by -
penetration of renal capsule.
extensive invasion of the renal sinus.
Vessels outside renal parenchyma involved (eg – renal sinus).
NOTE :completely resected and margins are free
of tumor

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Stage III
• Microscopic or gross residual or unresectable non-
hematogenous tumor.
• Confined to the abdomen.
• Evidenced by : any of the following-
 lymph node involvement
 peritoneal involvement
 margins of resection +
 Partially resectable
 tumor spillage during surgery
 biopsy taken prior surgery
 tumor removed in more than one piece.

26. 38
Stage IV
● Hematogenous metastases (i.e., lung, liver,
bone, brain)
Or
lymph node metastases .
Adrenal is not included.

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Stage V
●
Bilateral Tumor (at the time of diagnosis).

28. Other important criteria :
• Anaplasia is an aggressive pathological feature.
• LOH 1p 16q is predictive for increased risk of
relapse.
• Unfavorable histologies such as clear cell
and rhabdoid of the kidney.

29. Treatment

30. 48
Multimodality Management: Why?
●
●
● Surgery to remove the bulk of the disease followed by
Chemotherapy to eliminate metastatic disease forms the
basis of therapy .
● Radiation therapy is now a days indicated in a selected few
to eliminate the risk of local recurrence.
Wilms Tumors are highly chemo and radiosensitive.
However they typically present with a large size and have
a propensity for metastasis (hematogenous).

31. 49
Management Protocol
●
Management protocol varies according to:
–
–
–
–
Age of patient
Preoperative extent on imaging
Operative stage
Post operative histology

32. TREATMENT OUTLINE
• Patients are classically treated with immediate nephrectomy
followed by adjuvant Chemotherapy as per the stage and
histological features.
• Radiation therapy is delivered according to the abdominal stage.
• Radiation therapy and Chemotherapy are classically avoided in
very young infants (< 6 months)

33. NEOADJUVANT CHEMOTHERAPY:
 Indicated is some select situations like: – Tumor is deemed
inoperable:
● Tumor thrombus in Rt Atrium / IVC
● Extensive tumor with anticipated morbidity
● Invasion of surrounding organs (Liver/ Spleen/ intestines)
 Disseminated disease (Stage IV)
 WT occurring in some special situations:
● Bilateral WT
● WT in unilateral kidney
● WT in presence of genetic syndromes
● WT in horseshoe kidneys

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Surgery
–
• Unilateral radical nephrectomy
• Selective sampling of nodes (paraaortic, coeliac, iliac.)
• Renal vein and IVC (6% involvement) should be palpated
to exclude intravascular tumor extension
• Exploration of the opposite kidney(no longer done
routinely)

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●
Role of nephron-sparing surgery
bilateral Wilms tumor
genetic predisposition
solitary functional kidney / renal failure
< 6 months age
–
–
–
–
–
●
Role of biopsy of opposite kidney
– there is suspicion of nephrogenic rests (on preop imaging) in
opp kidney.
– Not to be use routinely, however part of protocol in NTWS 1-4

36. Initial NEPHRECTOMY IN ALL
VERY LOW
I,<2 yrs, <550gms
OBSERVATION
LOW
I, >2yrs, >550 gms
II, NO LOH(both 1p & 16q)
VA
STANDARD
I-II + LOH VAD
III + NO LOH RT------> VAD
IV + NO LOH RT------> VAD
(rapid responders of lung mets at 6 weeks from VAD– no
RT)
HIGHER
III + LOH RT---->VAD/C/E
IV + LOH RT---->VAD /CE + whole
lung RT n RT to mets
IV +No LOH(slow responders)
FH

37. Initial NEPHRECTOMY IN ALL
HIGH RISK
I-IV FOCAL
I DIFFUSE
I-III CLEAR
RTVAD
or
RTAlt VDC/CE
(clear cell)
HIGHEST
RISK
II-IV DIFFUSE
IV – CLEAR
I-IV RHABDOID
RTalt VDC/CPE-->
RT to mets
UNFAVOURABLE
HISTOLOGY

38. COG RT SUMMARY
STAGE ROLE OF RT
I-II FH NONE
III FH
I-III FOCAL
I-II DIFFUSE
10.8 Gy to flanks
Whole abdomen RT indicated if diffuse tumor spillage, pre-op or
intraperitoneal tumor rupture, peritoneal tumor seeding, and cytology +
ascites. Gross residual disease after surgery should receive 10 Gy boost
III DIFFUSE 19.8 Gy to flanks
Whole abdomen RT indicated if diffuse tumor spillage, pre-op or
intraperitoneal tumor rupture, peritoneal tumor seeding, and cytology +
ascites. Gross residual disease after surgery should receive 10 Gy boost
RT should be started by day 9 post op

39. Conditions Role of RT
Recurrent abdominal tumor 12.6–18 Gy (for <12 months)
or
21.6 Gy, if previous RT dose ≤10.8 Gy.
Boost dose up to 9 Gy to gross residual tumor after
surgery
Lung mets 12 Gy/8# to whole lung
Brain mets 30.6 Gy/17# to whole brain .
or
21.6 Gy to whole brain + 10.8 Gy boost
Liver mets 19.8 Gy/ 11# to whole liver
Bone mets 25.2 Gy to lesion + 3 cm margin
Unresected lymph node mets 19.8Gy

40. FLANK RADIATION

41. SURFACE MARKING : ANTERIOR

42. SURFACE MARKING : POSTERIOR

43. FLANK RADIATION:

44. WHOLE ABDOMEN RADIATION

45. WAR :

46. LUNG BATH :

47. • Patient supine, in mold for reproducibility.
• Anesthesia(if required).
• Contours*:
– GTV – recapitulate location of tumor. This contour will now extend into liver or spleen
and bowel that was displaced preoperatively.
– CTV – Expansion of 1 cm three-dimensionally.
– PTV – Institutional preference and physician comfort with reproducibility of set up. The
general range from 0.5 cm to 1.5 cm.
• OAR:
– Contralateral kidney (D100% ≤14.4 Gy)
– Femoral heads (V20 < 30%)
– Heart (Dmean < 26Gy)
– B/L whole Lung (9 Gy (age <1.5 years) or 12 Gy (age >1.5 years))
– Spinal Cord (Dmax < 45 Gy)
_ Liver: uninvolved liver, D50% ≤19.8 Gy; with liver metastases, D75% ≤30.6 Gy

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Bilateral Wilms Tumor
●
●
●
●
●
Account for 7% of all WT – 6% synchronous
Associated in 20% with genetic syndromes
Metachronous tumors fare worse than synchronous
Long term survival rates 70 -80%.

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Conclusion
●
MC renal tumor of childhood
●
●
●
● Radiation therapy given judiciously can reduce recurrences
Usually has a large size on presentation andhigh chance of
distant spread
However prognosis excellent with modern day therapy
Surgery with adjuvant chemotherapy vs neo-adjuvent chemotherapy
is the mainstay of therapy