Wilms Tumour PI Wilms #1 Protocol Dr Jane Skeen

chemotherapy (+ / - radiotherapy stages III/IV) Wilms Tumour mostly unilateral painless abdominal mass + / - haematuria treatment surgery chemotherapy (+ / - radiotherapy stages III/IV) 80% OS

Stages I Confined to kidney, completely resected, renal capsule intact II Tumour completely resected, tumour extends beyond kidney (penetration capsule, invasion renal sinus) III Spread beyond kidney but confined to abdomen IV Haematogenous metastases (lungs, liver, bone, brain) V Bilateral renal involvement by tumour

Starship Blood and Cancer Centre Histology Stage 10yr OS % Favourable 95% I 96 II 93 III 89 IV 81 V 78 Anaplastic (Unfavourable) 5% II-III 49 18 Starship Blood and Cancer Centre

Solid tumour kidney- arises from immature kidney cells (nephrogenic rest) 4th most common childhood cancer M=F Usually < 8 years (also adult Wilms) 1 in 8000-10,000 children Genetic predisposition in a few (1.5% familial) Associated conditions (congenital abnormalities)

Syndromes WAGR (wilms,aniridia,genitourinary/mental retardation Denys-Drash Beckwith Wiedemann (overgrowth disorder) Hemihypertrophy Association with Assisted ReproductiveTechnology Bilateral in 5-10% cases – multiple tumours

Two approaches COG (AREN)- based on NWTS- surgery up front unless inoperable SIOP - Pre-and post-op chemotherapy No biopsy at diagnosis Surgery around week 6

TREATMENT PLAN- Fiji Complete investigations/ workup as per protocol. Check BP. Discuss with Chch team Radiological (CT chest/abdomen) diagnosis of Wilms –biopsy not indicated Ensure appropriate chemotherapy in country Pre-operative chemotherapy VCR/ACT-D Reimage week 5 then proceed to surgery –ideally at week 6 Histology review (NZ) Post surgery chemotherapy VCR/ACT-D +/- DOXO, dependent on histology and stage, at CWMH or Lautoka

TREATMENT PLAN- Tonga and Samoa On imaging suspicion of Wilms tumour, image and arrange transfer to Starship, Auckland, NZ as soon as feasible. Decision will then be made whether nephrectomy possible. If up front nephrectomy, post operative chemotherapy dependent on stage. If inoperable pre-operative chemotherapy (VCR/ACT-D/DOXO) given, then reimage week 5 with surgery at week 6. To return to island of referral, once clinically stable from nephrectomy and initial chemotherapy (either VCR/ACT-D or VCR/ACT-D/DOXO) and completion of radiotherapy (if indicated) Chemotherapy to return with patient

PI WILMS #1 Protocol (Source NWTS 4) STAGE I and II FAVORABLE HISTOLOGY REGIMEN EE-4A WEEK 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 A A A A A A A V V VV V V V VVV V* V* V* A - DACTINOMYCIN (45 MCG/KG, IV) V - VINCRISTINE (0.05 MG/KG, IV) V* - VINCRISTINE (0.067 MG/KG, IV)

PI WILMS #1 Protocol STAGE III and IV FAVORABLE HISTOLOGY OR FOCAL ANAPLASIA REGIMEN DD-4A WEEK 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A D+ A D+ A D* A D* A V V V V V V V V V V V* V* V* V* V*   XRT   A - DACTINOMYCIN (45 MCG/KG, IV) D* - DOXORUBICIN (1.0 MG/KG, IV) D+ - DOXORUBICIN (1.5 MG/KG, IV) V - VINCRISTINE (0.05 MG/KG, IV) V* - VINCRISTINE (0.067 MG/KG, IV) XRT - RADIATION THERAPY

Tumour ?Wilms thought to be operable. Repeat CT scan done TTM PF August/September 2011: presented to surgeons TTM, Samoa, with an increasing abdominal mass of 2 months duration causing respiratory compromise Imaged with CT scan November: CT scan discussed at weekly Starship Paediatric Oncology MDM conference- no rupture seen Tumour ?Wilms thought to be operable. Repeat CT scan done TTM 24 November: Surgery Samoa - L)nephrectomy/splenectomy (Mr James Hamill, Starship) Histology :Wilms Stage III FH

PF December 2011 –funding approved December- arrived NZ, immunised (Hib, Men C, PCV 13,quad meningo) then commenced chemotherapy as per PI Wilms #1 protocol (3 drugs) January 2012 whole abdomen RT December-February 10 weeks chemotherapy 29 February 2011 returned to Samoa 7 March- ongoing chemotherapy TTM ( 3 weekly x 5 till week 24)

PI WILMS #1 Protocol STAGE III and IV FAVORABLE HISTOLOGY OR FOCAL ANAPLASIA REGIMEN DD-4A WEEK 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A D+ A D+ A D* A D* A V V V V V V V V V V V* V* V* V* V*   XRT   A - DACTINOMYCIN (45 MCG/KG, IV) D* - DOXORUBICIN (1.0 MG/KG, IV) D+ - DOXORUBICIN (1.5 MG/KG, IV) V - VINCRISTINE (0.05 MG/KG, IV) V* - VINCRISTINE (0.067 MG/KG, IV) XRT - RADIATION THERAPY

Late Effects Anthracycline exposure: Doxorubicin dose 3.5mg/kg (equivalent to 105mg/m2)-Recommend 5 yearly ECHO Radiation: Whole abdomen 10.5 gy in 8 fractions 09/01-17/01/2012. Single right kidney- urine dipstik Splenectomy- reimmunised+ prophylactic Amoxil Annual clinical reviews- imaging not indicated

July 2016 (5 years off treatment)