Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol.

Raquel Dávila Fajardo,Harm Van Tinteren,Xavier Muracciole,Gema L Ramírez Villar,Norbert Graf,Daniel Saunders,Claudia Pasqualini,Arnauld C Verschuur,Marry M Van Den Heuvel-Eibrink,Geert O Janssens,Kathy Pritchard-Jones,Rhoikos Furtwängler,Beatriz De Camargo,Patrick Melchior,Martine Van Grotel,Christian Rübe,Reem Al-Saadi

doi:10.3390/cancers13050976

Abstract

Simple SummaryAround 15–20% of all Wilms tumour (WT) patients present with metastatic disease. Approximately 10% of these patients achieve complete necrosis after preoperative chemotherapy, which is associated with a favourable prognosis. The aim of this observational study is to describe the outcome of metastatic patients with completely necrotic (low-risk histology), local stage III WT treated according to the SIOP 2001 protocol, whether or not postoperative radiotherapy was applied.Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.

Highlights

The Wilms tumour (WT), or nephroblastoma, is the most frequent paediatric renal tumour, which accounts for 80–90% of all tumours of the kidney in childhood [1]
Between June 2001 and December 2017, 703 patients with metastatic WT were included in the SIOP 2001 study
Forty-five had lung metastases (11 of them combined with other localisations), one patient had liver/peritoneal metastasis only, and one patient had a tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism only

Summary

Introduction

The Wilms tumour (WT), or nephroblastoma, is the most frequent paediatric renal tumour, which accounts for 80–90% of all tumours of the kidney in childhood [1]. The focus on improving risk stratification adapted treatment has resulted in an increased overall survival (OS) for patients with WT. Long-term OS exceeds 90% in localised disease and 80% in metastatic patients [4,6–9]. In the SIOP 9 study, the OS rate of patients with completely necrotic stage IV disease was 100% [10,11]. Patients undergoing resection of lung metastases show high survival rates if no vital tumour cells are found in the specimen [4,8]. Since the introduction of the SIOP 2001 protocol, this excellent outcome has resulted in the omission of abdominal radiotherapy in patients with localised disease, completely necrotic stage III. Whether radiotherapy to the primary tumour area or to the metastatic sites is required in the case of patients with metastatic disease and completely necrotic, local stage III WT has never been assessed

Methods

Results

Conclusion