Results of Treatment for Patients With Multicentric or Bilaterally Predisposed Unilateral Wilms Tumor (AREN0534): A report from the Children's Oncology Group

Abstract

Background A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to facilitate partial nephrectomy in 25% of children with bilaterally predisposed unilateral tumors (Wilms tumor/aniridia/genitourinary anomalies/range of developmental delays [WAGR] syndrome; and multifocal and overgrowth syndromes). The purpose of this prospective study was to achieve excellent event‐free survival (EFS) and overall survival (OS) while preserving renal tissue through preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response. Methods The treating institution identified whether a predisposition syndrome existed. Patients underwent a central review of imaging studies through the biology and classification study AREN03B2 and then were eligible to enroll on AREN0534. Patients were treated with induction chemotherapy determined by localized or metastatic disease on imaging (and histology if a biopsy had been undertaken). Surgery was based on radiographic response at 6 or 12 weeks. Further chemotherapy was determined by histology. Patients who had stage III or IV disease with favorable histology received radiotherapy as well as those who had stage I through IV anaplasia. Results In total, 34 patients were evaluable, including 13 males and 21 females with a mean age at diagnosis of 2.79 years (range, 0.49‐8.78 years). The median follow‐up was 4.49 years (range, 1.67‐8.01 years). The underlying diagnosis included Beckwith‐Wiedemann syndrome in 9 patients, hemihypertrophy in 9 patients, multicentric tumors in 10 patients, WAGR syndrome in 2 patients, a solitary kidney in 2 patients, Denys‐Drash syndrome in 1 patient, and Simpson‐Golabi‐Behmel syndrome in 1 patient. The 4‐year EFS and OS rates were 94% (95% CI, 85.2%‐100%) and 100%, respectively. Two patients relapsed (1 tumor bed, 1 abdomen), and none had disease progression during induction. According to Response Evaluation Criteria in Solid Tumor 1.1 criteria, radiographic responses included a complete response in 2 patients, a partial response in 21 patients, stable disease in 11 patients, and progressive disease in 0 patients. Posttherapy histologic classification was low‐risk in 13 patients (including the 2 complete responders), intermediate‐risk in 15 patients, and high‐risk in 6 patients (1 focal anaplasia and 5 blastemal subtype). Prenephrectomy chemotherapy facilitated renal preservation in 22 of 34 patients (65%). Conclusions A standardized approach of preoperative chemotherapy, surgical resection within 12 weeks, and histology‐based postoperative chemotherapy results in excellent EFS, OS, and preservation of renal parenchyma.

Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: The 30‐year SIOP‐RTSG experience

“…In patients with a genetic predisposition such as WAGR syndrome, preoperative chemotherapy is relevant to facilitate NSS. 11 However, we observed a high rate of progressive or nonresponsive tumors, which were frequently of the stromal subtype, as has been previously reported. 29 For patients suspected of bilateral nephroblastomatosis, it is challenging to decide whether or not, and at which time point, surgery should be performed, with the risks of disease progression being balanced against a loss of renal function.…”

“…In patients with a genetic predisposition such as WAGR syndrome, preoperative chemotherapy is relevant to facilitate NSS 11 . However, we observed a high rate of progressive or nonresponsive tumors, which were frequently of the stromal subtype, as has been previously reported 29 .…”

“…However, the characteristics and outcomes of patients with WAGR and WT registered for the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) protocols, according to which preoperative chemotherapy is administered, have never been described. Currently, also in North American treatment protocols (Children's Oncology Group), preoperative chemotherapy is recommended for children with a genetic predisposition 11 . Here, we report the clinical and tumor characteristics and outcomes of patients with WAGR syndrome who developed WT and/or nephroblastomatosis and were identified through the 2 last SIOP‐RTSG protocol registries and the SIOP‐RTSG network in order to support surveillance and treatment recommendations.…”

TRIM28 variants and Wilms' tumour predisposition

“…The two classification systems apply to WTs treated with primary surgery and preoperatively treated WT, respectively [17]. Generally, preoperative chemotherapy is recommended in SIOP Renal Tumour Study Group (RTSG) protocols for all children aged ≥6 months at diagnosis [18], while in North American COG protocols it is only recommended for children with a known genetic predisposition and/or bilateral WT [19]. In most cases after preoperative chemotherapy, part of the tumour has become necrotic and because the undifferentiated, blastemal cells are more sensitive to chemotherapy, the initial composition of epithelium, stroma, and blastema may have shifted [20].…”

Болалардаги Буйрак Ўсмалари Ҳақида Умумий Маълумотлар (Нефробластома)

“…Various molecular mechanisms underlying Beckwith-Wiedemann syndrome have been identified. Some of these abnormalities are genetic (germline mutations of the maternal allele of CDKN1C, paternal uniparental isodisomy of 11p15, or duplication of part of the 11p15 domain) but are more frequently epigenetic (loss of methylation of the maternal ICR2/KvDMR1 or gain of methylation of the maternalICR1) [5,16].…”