CLINICAL MANAGEMENT GUIDELINES RENAL TUMOURS To be used in conjunction with the Umbrella Study Protocol Dr Sucheta J Vaidya Dr Lisa Howell Dr Tanzina Chowdhury Dr Minou Oostveen Dr Cat Duncan Mr Mark Powis Mr Bruce Okoye Dr Daniel Saunders Professor Gordan Vujanic Professor Kathy Pritchard Jones On behalf of the CCLG Renal Tumour Special Interest Group January 2020 The CCLG does not sponsor or indemnify the treatment detailed herein. These treatment recommendations are provided by the CCLG Renal Tumours Special Interest Group to inform and for use at the sole discretion of treating clinicians who retain professional responsibility for their actions and treatment decisions. Treatment recommendations are based on current best practice and not what is necessarily proposed for any forthcoming clinical trial. CCLG Clinical Management Guidelines: Renal Tumours - January 2020 1 [This page is blank on purpose] CCLG Clinical Management Guidelines: Renal Tumours - January 2020 2 TABLE OF CONTENTS 1. Background and Rationale ............................................................................................. 8 2. Specific Objectives of CCLG Clinical Guidelines ............................................................. 10 3. Guideline Recommendations ....................................................................................... 10 3.1 Diagnostic work up guidelines for renal tumours ................................................................. 10 Clinical work-up ........................................................................................................................................... 10 Laboratory work-up ..................................................................................................................................... 11 Radiological work-up- Refer to UMBRELLA CLINICAL TRIAL ........................................................................ 11 Role of biopsy .............................................................................................................................................. 12 Checklist for indications for biopsy in children over 6 months of age and < 7 yrs. ..................................... 12 3.2. Treatment guidelines for localised Wilms Tumours (stage I-III) ........................................... 14 Pre-operative chemotherapy for localised unilateral tumour .................................................................... 14 Fig 1. PRE-OPERATIVE CHEMOTHERAPY FOR LOCALISED DISEASE .............................................................. 14 Chemotherapy dose adjustment for infants and/or < 12 kg body weight .................................................. 15 Table 1- Dosage of drugs – Chemotherapy dose adjustments for infants and /or <12 kg body weight .... 15 Post-operative treatment for localised tumour .......................................................................................... 15 Table 2: Overview of post-operative treatment for localised disease ........................................................ 16 Dose Modifications of chemotherapy During radiotherapy ....................................................................... 16 Fig 2. REGIMEN AV1 .................................................................................................................................... 20 Fig 3. REGIMEN AVD(loc) ............................................................................................................................. 21 Fig 4. REGIMEN AV2 .................................................................................................................................... 22 Fig 5. REGIMENT HR-1(LOC) ........................................................................................................................ 23 3.3 Treatment guidelines for Metastatic Tumours ..................................................................... 24 Summary of changes when compared to previous CCLG guidelines: ......................................................... 24 Pre-operative chemotherapy ...................................................................................................................... 25 Pre-operative Reassessment of metastasis ................................................................................................. 25 Table 3: Definition of metastatic response after pre-operative chemotherapy ......................................... 25 Surgery ........................................................................................................................................................ 26 Post-operative chemotherapy ..................................................................................................................... 26 Treatment schedules for Stage IV ............................................................................................................... 30 Table 4: Treatment overview for stage 4 Wilms ......................................................................................... 31 Radiotherapy ............................................................................................................................................... 35 Follow-up ..................................................................................................................................................... 35 Fig 6: PRE-OPERATIVE CHEMOTHERAPY FOR METASTATIC DISEASE .......................................................... 36 Fig 7: POST -OPERATIVE CHEMOTHERAPY AVD 150 .................................................................................... 37 Fig 8: POST OPERATIVE TREATMENT -AVD 250 ........................................................................................... 38 Fig 9: POST OPERATIVE TREATMENT- HRm ................................................................................................. 39 4 Supportive Care ........................................................................................................................................ 40 3.4 Management of bilateral disease (stage V) and bilaterally-predisposed unilateral Wilms Tumour ..................................................................................................................................... 41 Table 5: CONDITIONS WITH AN INCREASED RISK OF WILMS TUMOUR ...................................................... 41 Summary of changes ................................................................................................................................... 41 Rationale for the current guideline in Bilateral Wilms Tumour (BWT) ....................................................... 42 CCLG Clinical Management Guidelines: Renal Tumours - January 2020 3 Chemotherapy guidelines ........................................................................................................................... 44 Treatment plans .......................................................................................................................................... 45 Fig 10: Patients with bilateral Wilms Tumour ............................................................................................. 46 Fig 11: Patients with unilateral Wilms Tumour and contralateral nephroblastomatosis ............................ 47 Fig: 12 Patients with bilateral or unilateral nephroblastomatosis .............................................................. 48 FIG 13: Patients with unilateral tumour and predisposition syndrome as cited previously ........................ 48 Recommendations for frequently asked questions .................................................................................... 49 References ................................................................................................................................................... 50 3.5 Treatment guidelines after primary surgery ........................................................................ 52 Summary of changes (compared to previous guidelines) ........................................................................... 52 Staging ......................................................................................................................................................... 52 HISTOLOGICAL CLASSIFICATION .................................................................................................................. 52 Chemotherapy regimen .............................................................................................................................. 53 3.6 Treatment guidelines for relapsed Wilms tumours .............................................................. 56 Treatment guidelines for relapsed Wilms tumour (Key points and summary of changes from previous guidance according to UKWR. ..................................................................................................................... 56 Diagnostic and staging investigations at relapse ......................................................................................... 57 Risk grouping ............................................................................................................................................... 58 FIG 14: Flow diagram with treatment recommendations for relapsed wilms ............................................ 59 Therapeutic recommendations ................................................................................................................... 59 Group AA ....................................................................................................................................................