Updated by Jennifer Logan

1. What is the estimated annual incidence of Wilms tumor (WT) in the United States?  

2. What is the median age at Dx?  

3. Is there a sex predilection?  

4. How does the age of presentation differ with Wilms when compared to neuroblastoma (NB)?  

5. What is the age of presentation for hereditary/bilat tumors?  

6. Name 3 genetic syndromes associated with Wilms.  

7. What is WAGR syndrome, and what is the associated genetic change?  

8. What is Denys-Drash syndrome, and what is the associated genetic change?  

9. What is Beckwith-Wiedemann syndrome, and what is the associated genetic change?  

10. What transcription factor is important for normal kidney/gonadal development and is associated with Wilms?  

11. What is the function of WT2?  

12. What are the other genetic defects seen in Wilms?  

13. Name 1 paternal and 1 maternal environmental risk factor for WT.  

14. What are some poor prognostic factors seen in Wilms?  

15. What histology has the worst outcome in Wilms?  

16. What study demonstrated the prognostic importance of LOH 1p16q for Wilms?  

17. What are the UH subtypes in Wilms?  

18. How is focal anaplasia (FA) defined?  

19. What renal tumors are not WT but are treated similarly to WTs?  

20. What are the 4 sets of criteria used to define DA?  

21. What is the stage-by-stage 4-yr OS for anaplastic/UH WT?  

22. How does the 4-yr OS compare b/t focal and diffuse anaplasia?  

23. What are the typical presenting Sx in Wilms? How does this compare to NB?  

1. What is the typical workup for an abdominal mass of unclear etiology in a child?  

2. What is the recommended 1^st-line imaging modality for an abdominal mass?  

3. Pts with what histologic subtype(s) require bone scan?  

4. With a Dx of Wilms, what 2 chest imaging modalities can be employed for staging purposes?  

5. Pediatric pts with what renal tumors need BM Bx?  

6. Pediatric pts with what renal tumors require MRI of the head as part of their workup?  

7. What is the typical appearance of WT on CT?  

8. Under what circumstances should Bx be performed?  

9. On what issues should the surgeon comment at the time of Sg?  

10. What % of pts present with each of the features summarized in this table?  

11. What are some common sites of mets?  

12. How commonly is calcification seen in Wilms?  

13. How many stages are there in Wilms?  

14. Summarize the staging of WT.  

15. Is adrenal involvement considered a met?  

1. What is the Tx paradigm for WT in the United States?  

2. What is the major difference b/t the International Society of Pediatric Oncology (SIOP) Tx paradigm (European Cooperative Group) and the National Wilms Tumor Study (NWTS) paradigm (American Cooperative Group)?  

3. Under what circumstance is the SIOP paradigm favored in the United States?  

4. What are the indications for postop RT in the current COG protocols (AREN0532,533)? (Table 3-1)  

   Table 3-1: Current Childrens Oncology Group Wilms Protocol (AREN0532/533)'s Oncology Group Wilms Protocol (AREN0532/533)

   Goals: Reduce Tx-related toxicity in low-risk tumors and improve outcome for high-risk tumors with chemo intensification.
   Tumor Risk Classification	Multimodality Treatment
   Very low risk FH WT >2 yrs, stage I FH, <550 g	Surgery, no therapy if central pathology review and LN sampling
   Low-risk FH WT	Surgery, no RT, regimen EE4A
   ≥2 yrs, stage I FH, ≥550 g
   Standard-risk FH WT	Surgery, regimen DD4A
   Stages I-II FH with LOH	Surgery, regimen DD4A
   Stage III FH without LOH	Surgery, RT, regimen DD4A
   Stages III-IV FH with LOH (AREN0533)	Surgery, RT, regimen M, WLI
   Stage IV FH (slow/incomplete responders)
   Stage IV FH: CR of lung mets at wk 6/DD4A (rapid early responders)	Surgery, RT, regimen DD4A; no WLI
   Stages I-III FA	Surgery, RT, regimen DD4A
   Stage I DA
   Stage IV FA	Surgery, RT, regimen UH1
   Stages II-IV DA
   Stage IV CCSK
   Stage IV RTK
   Stages I-III CCSK	Surgery, RT, regimen 1

   FH, favorable histology; WT, Wilms tumor; LN, lymph node; RT, radiation therapy; LOH, loss of heterozygosity; WLI, whole lung irradiation; CR, complete response; FA, focal anaplasia; DA, diffuse anaplasia; CCSK, clear cell sarcoma of the kidney; RTK, rhabdoid tumor of the kidney.

5. What chemotherapeutic agents are typically used in Wilms? (Table 3-2)  

   Table 3-2: Chemotherapy Regimens on AREN0532/533 Protocols

   Regimen	Agents
   EE4A	VCR/AMD
   DD4A	VCR/AMD/ADR
   M	VCR/AMD/ADR; CY/ETOP
   I	VCR/DOX/CY; CY/ETOP
   UH1	CY/CARBO/ETOP; VCR/DOX/CY

   VCR, vincristine; AMD, dactinomycin; ADR, Adriamycin; CY, Cytoxan; ETOP, etoposide; DOX, doxorubicin; CARBO, carboplatin.

6. What did the early NWTS-1 and NWTS-2 studies show?  

7. Which study demonstrated that whole abdomen irradiation (WAI) is not needed for local spillage?  

8. Which study demonstrated that adding Adr to VA benefited group 2-4 pts?  

9. Which study demonstrated that 10 wks was equal to 6 mos of chemo for stage I pts?  

10. Which study showed that stage II FH pts do not need RT as long as VA is given?  

11. Which study eliminated Adr from stage II FH?  

12. Which study demonstrated that 10 Gy was equal to 20 Gy if Adr was added to stage III pts?  

13. Which study addressed the addition of Cytoxan to VAAdr for high-risk pts?  

14. Which study addressed pulse-intense (PI) chemo?  

15. What are the main advantages of PI chemo?  

16. Which study found that local spillage (old stage II) without RT results in a↑LR?  

17. What question does NWTS-5 address? (DomeJS et al., JCO 2006)  

18. For which pts did NWTS-5 show ↑ (13.5%) rates of relapse with nephrectomy alone and without adj chemo?  

19. What chemo regimen in NWTS-5 improved outcomes for stages II-IV with DA?  

20. Did stage I anaplastic tumors qualify for RT in NWTS-5?  

21. What do the current protocols (COG AREN0532, 0533) address?  

22. What were the factors that determine risk groups in the COG AREN0532/0533?  

23. What subset of pts on the current COG protocol could get Sg alone without adj Tx?  

24. What are the RT doses to the postop bed for Wilms pts ≥16 yo and/or those with rhabdoid and/or DA? How about for other pts? (Table 3-3)  

    Table 3-3: Radiation Planning and Doses on Protocols AREN0532/533

    RT timing: Concurrent with VCR, surgery day 1, RT ≤ day 10 (max day 14).

    Exception: Medical contraindication or delay in central pathology review.

    RT field design:

    I. Flank RT: GTV = preop CT/MRI (tumor and involved kidney). CTV + PTV = ≤1 cm

    Medial border across midline to include vertebral bodies + 1-cm margin but sparing contralat kidney. Other field borders placed at edge of PTV. Use AP/PA.

    If + PA and surgically removed, then treat entire PA chain to 10.8 Gy.

    If + residual Dz, then boost with 10.8 Gy after initial 10.8 Gy (3D-CRT, GTV = postop volume).

    Dose limits: Two-thirds contralat kidney to 14.4 Gy, one-half of undiseased liver to 19.8 Gy.

    II. WAI: CTV = entire peritoneal cavity from diaphragm to pelvic diaphragm.

    Superior border: 1 cm above dome of diaphragm.

    Inferior border: Bottom of obturator foramen.

    Laterally: 1 cm beyond lat abdominal wall; block femoral heads.

    Dose 10.5 Gy (1.5 Gy/fx) except for diffuse anaplasia or rhabdoid tumors (dose is 19.8 Gy, shield kidney to keep <14.4 Gy).

    III. WLI: CTV includes lungs, mediastinum, and pleural recesses. PTV = CTV + 1 cm.

    Inf border at L1, sup border 1 cm above 1st rib, block humeral heads.

    Can boost after 12 Gy (1.5 Gy/fx) (10.5 Gy for <12 mos) for persistent Dz after 2 wks →+7.5 Gy (19.5 Gy) to residual with conformal fields.

    IV. Liver mets: Surgery for solitary mets, excised to -margins. Whole liver RT for diffuse liver mets to 19.8 Gy (with additional 5.4-10.8 Gy at discretion).

    V. Brain: WBRT to 21.6 Gy (30.6 Gy if >16 yo). If 21.6 Gy → conformal RT boost with additional 10.8 Gy.

    VI. Bone: GTV + 3-cm margin, AP/PA to 25.2 Gy (30.6 Gy if >16 yo).

    VII. Unresected nodes: Cover entire LN chain to 19.8 Gy (30.6 Gy if >16 yo), with optional 5.4-10.8 Gy boost. If removed +PA LN, use 10.8 Gy to cover.

    RT, radiation therapy; VCR, vincristine; max, maximum; GTV, gross target volume; preop, preoperative; CT/MRI, computed tomography/magnetic resonance imaging; CTV, clinical target volume; PTV, planning target volume; cm, centimeter; contralat, contralateral; AP/PA, anterior-posterior/posterior-anterior; +, positive; Gy, gray; Dz, disease; 3D-CRT, three-dimensional conformal radiation therapy; postop, postoperative; WAI, whole abdomen irradiation; lat, lateral; fx, fractions; WLI, whole lung irradiation; inf, inferior; sup, superior; mos, months; wks, weeks; mets, metastasis; -, negative; WBRT, whole brain radiation therapy; yo, years old; LN, lymph node.

25. What are the indications and the RT doses for WAI?  

26. What are the indications for flank RT?  

27. What is the standard flank RT dose?  

28. What is the dose to unresected+LNs?  

29. What is the preferred Tx for localized liver mets? Diffuse liver mets?  

30. What dose is given to resected+LNs?  

31. At what age can pts rcv greater flank doses and greater doses to mets?  

32. When is whole lung irradiation (WLI) not required in a Wilms pt with lung mets?  

33. When is WLI indicated? What are the doses?  

34. What med should pts take when treated with WLI?  

35. How is bilat Wilms treated?  

36. RT should preferably start by which day and should begin no later than which day after Sg?  

37. How long is the chemo regimen for stages I-II and III-IV FH?  

38. What is the medial border of a flank field?  

39. What are the preferred RT margins/techniques for a flank field?  

40. What is the dose for brain mets?  

41. What is the dose for bone mets?  

42. How do you manage a pt who presents with mets and a resectable tumor?  

43. What is the outcome for relapsed Wilms treated with VA only for stage I or II Dz?  

44. What about relapsed stages III-IV Dz?  

1. What is the dose constraint for the kidney?  

2. What is the dose constraint for the liver?  

3. Pts are at risk for what late effects with flank RT? WLI?  

4. What is the risk of SBO at 15 yrs after flank/abdominal RT?  

5. What is the risk of a 2^nd malignancy at 15 yrs?  

6. The reirradiation tolerance of which organ decreases with time after initial RT?  

7. What is the TD 5/5 for an entire kidney?  

8. What is the cumulative max total dose (including prior RT) for WT pts?