Management of-wilms-tumors-9306 - copy

wilms tumor- pathology, presentation, management

1. Wilms' TumourWilms' Tumour
Moderator:Moderator:
Lt Col MS Vinod ( Cl Spl Surg & Paediatric Lt Col MS Vinod ( Cl Spl Surg & Paediatric
Surgeon)Surgeon)
Resident:Resident:
Dr SD SanyalDr SD Sanyal

2. Epidemiology
•Annual incidence in US = 7.6 cases/ million
( amongst children < 15 years)
•6% of Paediatric tumors
•Commonest abdominal pediatric tumor
•5
th
most common childhood cancer
•Frequency - Blacks > Asians
•Male to female ratio is:
•0.92:1.00 for unilateral disease
•0.60:1.00 for bilateral disease
2

3. Epidemiology
•Mean age of diagnosis:
•46.9 months for females (29.5 mths for B/L tumors)
•41.5 months for males (32.6 mths for B/L tumors)
•Scanty Indian population based data
•Largest study by Thiruanathapuram
- Wilms' Tumors account for 5.4% of all
pediatric malignancies
•Likely to be the 2
nd
most common solid
pediatric tumor in India (after HD)
3

4. 4
Pathogenesis

5. Renal Development
5
Metanephric blastema

6. Nephrogenic Rests
•Perinephric rests are
persistent
mesoblastic tissues
beyond the 36
th
week
of gestation
•Two types:
•Intralobular (assoc. with
WAGR, DDS etc)
•Perilobular (assoc. with BWS)
6

7. Wilms Tumorigenesis
7

8. Tumor Components
8

9. Tumor Components
•Blastema
•Mesenchyme
•Epithelium
9

10. Genetics of Wilms Tumor
•Three candidate gene loci :
•Chromosome 11p13 (WT-1 gene):
•WAGR syndrome
•Denys Drash Syndrome
•Chromosome 11q15(WT- 2 gene):
•Beckwith -Wiedemann Syndrome
10

11. Classification
•Favourable
- Contains well developed components
•Anaplastic
- Diffuse anaplasia present
11

12. Clinical Clinical
FeaturesFeatures

13. Symptoms
•Classically appears as a silent abdominal
mass during childhood (60-90%)
•Other symptoms:
•Pain Abdomen (30-40%)
•Flank pain and rapid enlargement of the mass (2° to bleeding in
the tumor)
•Hematuria (25%)
•Fever (20%)
13

14. Physical Examination
•Primary tumor
•Smooth, rounded lobulated mass in the
loin
•Attached kidney may be felt
•Doesn't move with respiration
•Other features:
•Hypertension (25%)
•Varicocele (tumor thrombus in IVC)
•Associated genitourinary abnormalities
•Associated stigmataof congenital
anomalies
14

15. Congenital Anomalies
• Congenital anomaly : 9 - 10% of individuals
with Wilms
• Long term F/U: Syndrome in 17% patients
15

16. WAGR Syndrome
16
Wilms TumorWilms Tumor
AniridiaAniridia
Genitourinary abnormalitiesGenitourinary abnormalities
Mental RetardationMental Retardation

17. Denys Drash Syndrome
17
Diffuse Mesangial SclerosisDiffuse Mesangial Sclerosis
Male Male
PseudohermaphorditismPseudohermaphorditism
Wilms TumorWilms Tumor

18. Beckwith-Wiedemann Syndrome
18
MicrocephalyMicrocephaly
Umbilical HerniaUmbilical Hernia
Ear lobe creaseEar lobe crease MacroglossiaMacroglossia
HemihypertrophyHemihypertrophy

19. WorkupWorkup

20. Investigations
20
◄ To establish the diagnosis
◄ Delineate tumor extent
◄ Confirm contralateral renal
functional status
◄ Discover any metastasis
◄ Assess fitness for surgery / anaesthesia
AIMS

21. Routine Investigations
•Hemogram:
•Anemia: 2° to tumor bleed
•Thromobocytosis: 2° to tumor bleed
•Coagulogram:
•Association with Von Willebrand Disease (5 -8%)
•Urinanalysis:
•Protein
•Catecholamines: Exclude neuroblastoma & for anesthesia
•Renal Function

22. Imaging
•USG abdomen:
•Imaging investigation of choice for
local disease
•Organ of origin,
•Extent of any spread
•Patency of the IVC
•Detecting any involved lymph
nodes
•To assess renal function:
•IVP
•DTPA renal scan
•CT - IVP
•CT scans:
•Accurate delineation of intra-
abdominal tumor.
•Extension into surrounding organs
•Detection of lung mets (?)
•Plain X-rays:
•PA views are adequate for
detection of lung mets.
22

23. Special investigations
•CT brain:
•Rhabdoid tumor of kidney
•Bone scan:
•Clear cell sarcoma
23

24. D/D of Pediatric Renal Mass
•Neuroblastoma
•Hydronephrosis
•Renal cell carcinoma
•Multilocular cystic renal tumor
•Clear cell sarcoma
•Rhabdoid tumor
•Renal medullary carcinoma
•Ossifying renal tumor of
infancy
•Lymphoma.
•Nephroblastomatosis
•Mesoblastic nephroma
•Angiomyolipoma,
•Metanephric adenoma,
24

25. StagingStaging

26. Stage I
•SIOP System:
•Tumor
confined to
the kidney
•Completely
excised
•Capsule intact
26
Tumor
NWTS System:
Tumor confined to
the kidney
Completely excised
Capsule intact

27. Stage II
•SIOP System
•Tumor extending beyond
the kidney
•Extra-renal vessel /ureteric
invasion
•Adjacent organ or vena
caval invasion
•Regional lymph node
involvement (IIN)**
•Resected completely
27
Tumor
NWTS System
Local extension beyond the
renal capsule
No invasion of adjacent
viscera / mets
Only microscopic residual
tumor
Tumor in renal vessels not
beyond the renal sinus
Bx before resection (except
FNAC)**
Completely resected

28. Stage III
•SIOP System:
•Invasion beyond capsule
with incomplete excision
•Pre/peri-op Bx
•Peritoneal mets
•Pre/per-op rupture
•PAN below renal artery
origin
28
NWTS System:
Macroscopic residual
disease in nodes &/or
abdomen
Preop rupture
Diffuse spillage
Peritoneal implants

29. Stage IV
•SIOP System:
•Hematogeno
us metastasis
•LAD beyond
the
abdomen/pel
vis
29
NWTS System:
Hematogenous
metastasis
LAD beyond the
abdomen/pelvis

30. Stage V
•SIOP System:
•Bilateral
tumor
30
NWTS System:
Bilateral Tumor
N.B.: Both systems specify that the tumors should be individually staged.

31. Overview of the recent system
31

32. TreatmenTreatmen
tt

33. Multimodality Management
•Wilms Tumors = highly chemo and
radiosensitive
• Large mass and propensity for metastasis
(hematogenous)
• Surgery = bulk of the disease
• Chemotherapy = For metastatic disease
• Radiation therapy = eliminates the risk of
local recurrence
33

34. Treatment outline
Immediate Nephrectomy
Adjuvant Chemotherapy as per Stage and
Histological features
Radiation as per abdominal stage*
* Radiation generally avoided below 06 months

35. SurgerySurgery

36. Surgery
•Operability should be determined on the
table – imaging overestimates
inoperability
•Surgical excision is done through a
transverse abdominal incision
•The standard procedure includes:
•Unilateral radical nephrectomy
•Selective sampling of nodes (RPLND doesn't
alter outcome)
•Renal vein and IVC (6% involvement) should
be palpated to exclude intravascular tumor
extension
•Exploration of the opposite kidney
36

37. Issues in surgery
•Role of nephron-sparing surgery
•Indicated in bilateral Wilms tumor
•WT in patients with genetic predisposition
•Also in WT in solitary functional kidney / renal failure
•Always preceded by CCT
•Very young infants < 6 months age
•Role of biopsy of opposite kidney
•Condemned for unilateral involved kidney
•May be indicated in the opposite kidney if there is suspicion of nephrogenic
rests on preop imaging
•Not to be used routinely, however part of protocol in NTWS 1-4
37

38. Nephrectomy alone
•Presently indicated in:
•Age < 2 yrs
•Favourable Histology
•Stage I tumors
•Weight < 550 gms

38

39. Surgical Complications
•Surgical mortality  < 1%
• Complications of nephrectomy :
•Small bowel obstruction (7%)
•Hemorrhage (6%)
•Wound infection, hernia (4%)
•Vascular complications (2%)
•Risk factors associated with increased surgical complications:
•Higher local tumor stage
•Incorrect preoperative diagnosis
•Intravascular extension
•En bloc resection of other visceral organs
39

40. Post nephrectomy management
40
HistologyStage Chemotherapy Radiation therapy
FavourableI
Not needed
II
III – IV Stage adapted radiation therapy
I
Not needed
II
III–IV Stage adapted radiation therapy
I Not needed
II-IV Regimen I Stage adapted radiation therapy
CSSK I-IV Regimen I Stage adapted radiation therapy
I-IV Regimen RTK Stage adapted radiation therapy
Actinomycin D + Vincristine (EE4A)
Act-D + VCR+ Dox (DD4A)
Focal
Anaplasia
Actinomycin D + Vincristine (EE4A)
Act-D + VCR+ Dox (DD4A)
Diffuse
Anaplasia
Actinomycin D + Vincristine (EE4A)
Rhabdoid
Tumors

41. Chemotharapy

42. Chemotherapy
•Initially single agent Dactinomycin was used by
Faber et al in 1966.
•Tan et al showed that it was associated with a CR
rate of 37.5%
•Another study from UK in 1965 showed that
administration of 120 μg/Kg over 12 days improved
the 2 yr EFS from 11% to 62%
•Single agent Vincristine was also used in 1960s
•It was associated with an ORR of 61.5% in patients
with relapsed WT who had received Act-D
42

43. 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
• Unilateral kidney
• Presence of genetic syndromes
• Horseshoe kidneys
43

44. Neoadjuvant Chemotherapy
•The current protocol followed in the West
includes Actinomycin D + Vincristine
•4 weeks of chemotherapy = Adequate
• Some centres in India using 4-6 wks of
Vincristine + Etoposide prior to surgery

44

45. Radiation

46. Radiation Therapy
•Highly radiosensitive tumor
•Adjuvant radiotherapy = Survival
•In 1940s surgery attained 5 yr survival rates
of 15 -20% in all stages
•Addition of postoperative radiation therapy
increased the survival to 47% (Gross and
Neuhauser, 1940)
46

47. Role of Radiotherapy
•Historical
•Definitive radiation therapy
•Contemporary
•Preoperative Radiation
•Flank
•Whole Abdomen
•Postoperative Radiation
•Flank
•Whole Abdomen
•Lung bath
•Treatment of recurrence
•Abdomen (localized abdominal
recurrence)
•Treatment of metastasis
•Lung
•Brain
•Bone
•Liver
•Lymph nodes
47

48. 48
Wilms Tumor in
special situations

49. Relapsed / Refractory WT
•The most frequent site of relapse overall = Lung
•The overall survival following relapse = 24 -30 %
•Best results reported with:
- ICE regimen
 Ifosfamide
 Carboplatin
 Etoposide)
• Children + relapse - remission = High dose
chemotherapy + stem cell
transplantation(alternative)
49

50. Bilateral Wilms Tumor
•Account for 7% of all WT – 6% synchronous
•Associated in 20% with genetic syndromes
•Both sides staged seperately
•Metachronous tumors fare worse than
synchronous
•Long term survival rates 70 -80%.
50
Initial open biopsy / Trucut
biopsy and staging
Downstaging with
Chemotherapy
Bench Surgery*
Partial nephrectomy

51. Wilms Tumor in Adults
•Median age at presentation = 25 years
• MC presenting symptom  Pain
• Stage III and IV disease > in childhood
•Poor prognosis
•Survival = 24% at 3 years.
51

52. Wilms Tumor in Horseshoe Kidneys
•Abnormal fusion of metanephric blastema of
the lower pole of the future kidneys at 6
th
-7
th

weeks of gestation.
•50 -60 cases recorded in literature
•2 fold increased risk of development of WT
•Partial nephrectomy / bench surgery typically
used for reduction of disease burden
•Preoperative chemotherapy = Bulk reduction
•Post operative adjuvant radiation  involved
flank
52

53. Treatment toxicity
•Chemotherapy
•Vincristine: Neurotoxicity (7-8%)
•Actinomycin D: Hepatic Veno-occlusive disease
•Anthracyclines: Long term cardiotoxicity (10 -25% with cumulative doses of
300 mg/m
2
)
•Surgery
•32% have some renal dysfunction in opposite kidney after 10 yrs
•9% proteinuria
•11% hypertension
•Radiation therapy
•Loss in potential height (loss of potential height 7cm at 1 yr)
•Second malignancies
53

54. Follow up Protocol
54
Imaging Study Schedule
Abdominal ultrasound
CT chest
CT abdomen and pelvis
Starting 2 years from end of therapy: every 6 months × 4
Every 3 months × 4, then every 6 months × 2
Abdominal ultrasound or CT abdomen
Bone scan Every 6 months × 6
MRI brain Every 6 months × 6
Patient Character-
istics
Favorable-histology
Wilms' tumor
Chest radiograph CT chest Every 6 weeks until complete remission is documented; then
every 3 months × 8 times, then every 6 months × 4 times
Postoperatively after 6 weeks and 3 months; then every 3
months × 8, then every 6 months × 4
Anaplastic Wilms'
tumor; rhabdoid tu-
mor
Every 6 weeks until complete remission is documented; then
every 3 months × 8
Postoperatively after 6 weeks and 3 months; then every 3
months × 8
Abdominal ultrasound and chest ra-
diograph
MRI brain (for rhabdoid tumor only)
Clear cell sarcoma;
renal cell carcino-
ma
Chest radiograph or CT chestEvery 6 weeks until complete remission is documented; every
3 months × 8, then every 6 months × 6
Every 6 weeks until complete remission is documented; every
3 months × 8, then every 6 months 3 6

55. Thank YouThank You