Abstract
BackgroundTo enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols.MethodsPatients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93–01 and 2001 studies(1993–2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery.Results5631 patients were included; median age was 3.4 years(IQR: 2–5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5–85.5) and 93%(95%CI 92.0–93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10–18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4–10 years(HR 1.67, P = 0.01) and 10–18 years(HR 1.87, P = 0.04), but not for 2–4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors.ConclusionAlthough optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.
Highlights
As treatment for Wilms tumour (WT) is evolving towards further risk adaptation, there is an increasing interest in additional factors that can help to stratify treatment intensity based on the patient’s individual risk
Using previously described age categories, event-free survival (EFS) was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10 (HR 1.83, P
Optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and overall survival (OS) (4 years) in children with WT treated with pre-operative chemotherapy
Summary
As treatment for Wilms tumour (WT) is evolving towards further risk adaptation, there is an increasing interest in additional factors that can help to stratify treatment intensity based on the patient’s individual risk. Potential molecular prognostic markers such as copy number changes and loss of heterozygosity (LOH) of specific chromosomal regions are emerging.[9,10,11,12,13,14,15] Currently, in addition to tumour weight, LOH 1p/16q, stage and histology, the Children’s Oncology Group (COG) includes age in the risk stratification of its most recent protocols.[5, 7] So far, the independent prognostic significance of age has not been sufficiently validated in a large cohort of patients treated with pre-operative chemotherapy, as recommended in International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols (S1 Table). To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols
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