• Variation in adherence to protocol recommendations for pre- and post-operative treatment of children with Wilms tumour in two consecutive studies in the UK and Ireland

      Tugnait, S.; Al-Saadi, R.; Williams, R.; Oostveen, M.; Dzhuma, K.; Brok, J.; Irtan, S.; Lopez, A.; Weeks, M.; Bate, J.; et al. (2020)
      Background and Aims: Wilms tumour (WT) has excellent event-free and overall survival rates. However, small differences exist between countries participating in the same international study. This led us to examine variation in adherence to protocol recommendations as a potential contributing factor. Methods: Retrospective analysis of all children with unilateral WT treated with pre-operative chemotherapy in the SIOPWT2001 (2002- 11) and IMPORT (2012-18) studies in the UK and Ireland. Pre- and post-operative treatments (including radiotherapy) were classified as: per protocol (PP); deviation (PDEV) - variation for specified clinical rea- sons; violation (PVIOL) - not treated per protocol. Results: 1186 children with WT were registered by 20 centres. 983 (83%) had unilateral WT treated with pre-operative chemotherapy. All had centrally reviewed pathology. Case Report Forms (CRFs) allow- ing categorisation of the whole treatment pathway were available for 564 patients. Overall,58% (209/361) were treated PP in SIOPWT2001 and 67% (137/203) in IMPORT. A further 30% (110/361) and 17% (34/203) respectively classified as PDEV. PVIOL occurred in 12% (42/361) in SIOPWT2001 and 15% (31/203) in IMPORT. Stage III/IV tumours had higher proportion PVIOL (18% SIOPWT2001; 28% IMPORT) compared to stage I/II tumours (8% in both studies). The highest rates of PVIOL were in stage IV (metastatic) IMPORT patients (33%). The most common reasons for PVIOL were not changing to high risk chemotherapy, use of radiotherapy for slow metastatic responders and prolonged duration of pre-operative chemotherapy. For children with stage I/II WT, 92%/91% received PP pre-operative treatment and 79%/82% received PP post-operative treatment in SIOPWT2001/IMPORT respectively. Correlation of protocol adher- ence with survival is planned. Conclusions: Protocol guidelines are followed closely for stage I and II tumours but there is greater variation in more advanced disease. This maybe reduced by the more explicit definitions of metastasis and treat- ment response in the SIOP-RTSG UMBRELLA protocol that succeeded the IMPORT study in 2019