Optimal neoadjuvant chemotherapy duration in Wilms tumour with intravascular thrombus: A literature review and evidence from SIOP WT 2001 trial

Abstract

Introduction:Preoperative chemotherapy is recommended for children with Wilms tumour with intravascular extension. Extended chemotherapy may improve resectability, but increase tumour adherence to vascular endothelium, precluding complete resection. To evaluate the optimal length of preoperative treatment, we report a two-part review comprising systematic review of the literature and investigation of patients treated in the International Society of Paediatric Oncology (SIOP) WT 2001 trial. Methods: Studies were identified using Medline and Embase databases from 1996 to present. English language titles reporting management of intravascular Wilms tumour were analysed. Patients with Wilms tumour and thrombus were identified from the SIOP WT 2001 trial. Overall survival (OS) and event-free survival (EFS), tumour regression, completeness of resection and cavectomy were investigated. Results: The search retrieved 43 articles documenting 498 children. Note that 72% of the patients received neoadjuvant chemotherapy: 101 received standard course (4-6 weeks, standard course neoadjuvant chemotherapy [StC]) and 62 extended course (> 6 weeks, extended course neoadjuvant chemotherapy [EC]). There was no significant difference between the groups in terms of thrombus regression or completeness of resection. EFS was greater in the StC group (78 vs 54%; P = .04). Of 4511 patients registered in the SIOP WT 2001 trial, 166 had thrombus. Note that 97% of the patients received neoadjuvant chemotherapy: 63 StC and 67 EC. There was no significant difference between the groups with regard to tumour regression, complete resection, or cavectomy. Survival was significantly higher in those receiving StC than EC (OS: 95% vs 82%, P = .025; EFS: 88% vs 72%, P = .047). Conclusion:There is no evidence that prolonged courses of neoadjuvant chemotherapy beyond the recommended protocols confer any additional benefit in treating intravascular extension of Wilms tumour.

Impact of neoadjuvant chemotherapy on thrombus viability in patients with Wilms tumour and caval extension: systematic review with meta-analysis

“…A previous meta-analysis found no survival benefits to extended courses of chemotherapy in Wilms patients with intravascular extension, confirmed by the present study 27 . These longer courses of chemotherapy may reflect the lack of radiological regression of thrombus, indicating the absence of macro- or microscopic response, although a single study reported no association between macroscopic appearances and microscopic response 25 .…”

“…Logistic regression was used to analyse the relationship between thrombus viability and duration of chemotherapy, using data from individual patients where complete and amenable to comparison. Patients were then categorized by the duration of neoadjuvant chemotherapy as: short course, less than 4 weeks; standard course, 4–6 weeks; or extended course, more than 6 weeks 27 . Where the duration of neoadjuvant chemotherapy was reported in terms of cycles, courses, doses or protocols, standardized Wilms tumour regimens for the same agents were used to convert these terms to weeks, for adequate comparisons to be made.…”

Evidence-Based Surgical Guidelines for Treating Children with Wilms Tumor in Low-Resource Settings

“…Extending neoadjuvant therapy beyond 6 weeks is not associated with improved surgical resection, further thrombus regression, or survival advantage. 53 The panel recommends neoadjuvant chemotherapy for 6 to 12 weeks for patients with bilateral WT requiring nephron-sparing resection. (Strong recommendation; Quality of evidence: Very Low) Panel deliberation.…”

Inferior vena cava and right atrial thrombosis in children with embryonal tumors

“…Следует отметить, что несмотря на то, что наличие опухолевого тромбоза НПВ общепризнанно рассматривается как показание к проведению неоадъювантной химиотерапии, вопрос о ее длительности и количестве используемых препаратов остается открытым [26]. L. Morris и соавт.…”

“…Интересными в контексте описываемого случая явились данные о том, что гистологический тип опухоли влиял на частоту регресса опухолевого тромба, при этом сокращение размеров тромба у пациентов со стромальным вариантом нефробластомы было выявлено лишь в 17% случаев. В связи с этим в протоколе SIOP-RTSG 2016 при наличии опухолевого тромбоза НПВ у пациентов с локализованными формами нефробластомы рекомендовано проведение стандартной предоперационной химиотерапии по схеме AV в течение 4 нед [26].…”