wilms tumor is a common childhood renal malignancy, is now with better treatment options high cure rates, lets see some imp points

1. WILMS TUMOR
PRAGATHEESWARI G K

2. INTRODUCTION
• current cure rate of >90%.
• highly curable childhood neoplasm
• most common malignant renal tumor of childhood
• 3 and 4 years of age
• sporadic or hereditary tumors or in the setting of
specific genetic disorder

3. • WT1, which is a tumor suppressor gene at
chromosome 11p13
• play a specific role in glomerular and gonadal
development,WAGR syndrome, Denys-Drash
syndrome
• Beckwith Wiedemann syndrome maps to
chromosome 11p15.5; this locus is also referred to
as WT2.

4. • loss of heterozygosity (LOH) at 16q and 1p have
higher relapse and mortality rates.
• A novel WT suppressor gene on the X chromosome,
WTX
• Anaplastic tumors have shown changes on 17p
consistent with TP53 deletion and specific genomic
loss or underexpression on 4q and 14q and focal
gain of MYCN.1

5. • WT1 mutation and 11p15 LOH were significant
predictors of relapse in VLRWTs.
• gain of 1q is a promising biomarker for patients
with favorable histology
• Other molecular aberrations associated with
poorer outcomes included MYCN gain and TP53
loss

6. PATHOLOGY
• Histologically, WT reflects the development of the
normal kidney, consisting of three components,
blastemal, epithelial (tubules), and stromal elements, in
varying proportions
• Nephrogenic rests consist of embryonal nephroblastic
tissue and are found in 35% of kidneys with unilateral
WT and in nearly 100% of kidneys with bilateral WT
(BWT).
• greatest clinical significance in WT is anaplasia.
Anaplasia may be focal (FA) or diffuse (DA)
• distribution of anaplastic cells

7. CLINICAL FEATURES
• healthy child in whom abdominal swelling
• A smooth, firm, nontender massGross hematuria
occurs in as many as 25%
• hypertensive, malaise or fever
• anemia from haematuria

8. Work up
• Malignant childhood lesions of the kidney, neuroblastoma, and
benign conditions such as hydronephrosis, polycystic disease, and
splenomegaly in left-sided tumor
• USG -A specific advantage of ultrasonography is its ability to
assess vessels for flow and tumor thrombus with duplex and color
Doppler
• Abdominal CT scans can demonstrate gross extrarenal spread,
lymph node involvement, liver metastases, and the status of the
opposite kidney
• MRI -identifying renal origin and vascular extension of the tumor.
• Plain chest radiography and chest CT are also essential because
asymptomatic pulmonary metastases are common

11. STAGING

15. Timing of RT
• a delay of ≥10 days after surgery was associated with a significantly higher
abdominal relapse rate, particularly among patients with UH tumors
• D’Angio GJ, Evans AE, Breslow NE, et al. The treatment of Wilms’ tumor:
results of the National Wilms’ Tumor Study. Cancer 1976;38:633–646.
• . D’Angio GJ, Tefft M, Breslow NE, et al. Radiation therapy of Wilms’ tumor:
results according to dose, field, postoperative timing and histology.Int J Radiat
Oncol Biol Phys 1978;4:769–780.
• Thomas PRM, Tefft M, Compaan PJ, et al. Results of two radiotherapy
randomizations in the third National Wilms’ Tumor Study (NWTS-3). Cancer
1991;68:1703–1707.
Thomas PRM, Tefft M, Farewell VT, et al. Abdominal relapses in the Second
National Wilms’ Tumor Study patients. J Clin Oncol 1984;2:1098– 1101.ccording
• For the COG protocols, it is recommended that RT be given preferably by day 9
but no later than day 14 after surgery.

16. Radiation therapy volume

23. Bilateral wilms
• The current COG protocol (AREN0534) recommends earlier
biopsies or resection of nonresponsive tumors so that
ineffective therapies for patients with DA could be avoided.
• This study will intensify chemotherapy upfront (three drugs),
require second-look surgery at 6 weeks and definitive surgery
at 12 weeks, and recommend chemotherapy based on
histologic response after definitive surgery.
• RT is indicated for stage III FH tumors, stage I to III UH
tumors, or when chemotherapy and several surgeries do not
result in complete tumor resection with negative margins.
• Unlike in unilateral WT, the performance of a tumor biopsy or
the use of chemotherapy before definitive surgery is not an
indication for flank RT in BWT.

24. Summary of clinical trials

25. • NWTS (National Wilms Tumor Study Group)/ US
approach:
• Primary surgery
• Confirms pathological diagnosis
• Adjuvant treatment based on surgical staging
• Additional prognostic implication of surgical pathology
• SIOP (International Society of Paediatric Oncology /
/European approach: –
• Pre-operative chemotherapy approach
• Reduced spillage
• Tumor downstaging and improved surgical resectability
• Potentially avoids or reduces intensity of adjuvant therapy

26. • UK Children’s Cancer Study Group, UKW3
randomized trial:
Immediate nephrectomy vs Preoperative
Chemotherapy –
Improved stage distribution with preop Approach –
20% reduced use of radiotherapy or doxorubicin –
Similar event-free and overall survival and
distribution

27. • NWTS 1 (1969-74): – Post-operative RT not needed for stage I kids < 2
years age treated with AMD, but needed for older kids
• – Combined AMD and VCR better than either drug alone in stage II/ III
• NWTS 2 (1974-78): – ADR and VCR x 6 months may suffice for older
stage I kids, thereby avoiding RT – Adriamycin needed for stage II or
more
• NWTS 3 (1979-85): – 10 weeks AMD + VCR is sufficient (not 6 months)
in stage I, Favorable histol. (FH)
• – No RT needed for stage II, FH – 10 Gy equivalent to 20 Gy for stage
III, FH
• NWTS 4 (1986-94): – No RT randomizations in the study – Single dose
pulse intensive chemotherapy reduces hematological toxicity and
costs (compared to standard course 5 day course)
• NWTS 5 (1995-2002): – Identified LoH 16 q and 1p as negative
prognostic factor – Addition of etoposide improved outcomes in stage
II or more

29. • Recently completed COG renal protocols: –
AREN0532 - Very Low, Low & Standard Risk FH
Wilms –
• AREN0533 - Higher Risk FH Wilms – st III FH w/ LOH
or st IV FH
• Key RT study question: evaluated omission of lung
RT for patients with CR in lung to 6 weeks of chemo
& without LOH of 1p & 16q
• AREN0534 - Bilateral Wilms –
• AREN0321 - High Risk Renal Tumors (WT w/
anaplasia, clear cell sarcoma of kidney,malignant
rhabdoid tumor, renal cell carcinoma)

31. Nccn

39. Side Effects of Treatment
• • Acute: –
• Loose stools
• Nausea
• Fatigue
• Long term: –
1. Bowel adhesions –
2. Infertility (females > males) or future pregnancy complications •
3. Greater in females treated with whole abdomen with both ovaries and uterus in the field.
4. Scoliosis/vertebral body foreshortening
5. Hypertension - Secondary to fibrosis of contralateral renal artery
6. Renal failure (low incidence if treating flank)
7. CHF – risk is ~4% in patients receiving adriamycin1
8. Liver failure (chemotherapy associated)
9. 2nd malignancy (1.6% cumulative risk)

40. End stage renal disease
• The 20-year cumulative incidence of end-stage
renal disease among WT survivors after unilateral
nephrectomy on NWTS protocols was 74% for
children with Denys-Drash syndrome, 36% for
children with WAGR syndrome, 7% for children
with genitourinary anomalies, and 0.6% for
patients with none of these conditions.

41. Second malignant neoplasm
• 15-year cumulative risk of second malignant neoplasm
(SMN) was 1.6%. The risk of developing a lymphoma or
leukemia was 0.4% at 8 years, after which no cases
occurred later
• 73% of solid tumors arose within a previous RT
• the British Cancer Survivor Study__ the cumulative
incidence of a second primary neoplasm at 30, 40, and
50 years of age was 2%, 7%, and 12%, respectively
• In another NWTS report, female survivors who received
WLI had nearly a 15% risk of developing invasive breast
cancer by age 40 years

42. REFERENCE
• PEREZ AND BRADYS RADIATION ONCOLOGY
• NCCN GUIDELINES

43. • Testis dose :
https://www.ncbi.nlm.nih.gov/portal/utils/pageres
olver.fcgi?recordid=624ca50a9d7d003d8f76715f
• Tumor spillage
http://www.ncbi.nlm.nih.gov/pubmed/19395185?
https://ascopubs.org/journal/jcoTUmorAbstractpag
eresolver.fcgi
• https://www.ejcancer.com/article/S0959-
8049(20)31309-5/fulltext spleen Dose

44. THANK YOU