Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration

Abstract

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level.

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…The increasing use of chest CT as routine imaging for staging has resulted in the detection of small pulmonary nodules not visible on chest radiography (CT-only nodules). Similar to the COG protocol, CT-only nodules are included in the definition of lung nodules and treated as metastases in the UMBRELLA protocol if they have a transverse diameter of at least 3 mm (REFS 22,24,25).…”

“…Results from the COG National Wilms Tumor Study Group (NWTS)-4 and NWTS-5 trials showed that patients with CT-only nodules who were treated with vincristine and actinomycin D plus doxorubicin had superior EFS to those who received vincristine and actinomycin D only, but overall survival was similar in both groups 25 . Including CT-only nodules in the definition of metastatic disease will benefit patients with intermediate-risk or low-risk histology who achieve a rapid complete response of their CT-only nodules.…”

“…Detailed guidelines are provided for the stratification of postoperative chemotherapy, in which the cumulative dose of doxo rubicin has been lowered in order to reduce cardiac toxicity. The cumulative doxorubicin dose for patients with metastatic disease was 300 mg/m 2 in SIOP−2001, preliminary data from the COG AREN0533 trial suggest that using a cumulative doxorubicin dose of 150 mg/m 2 for patients with favourable histology does not considerably affect survival 25,26 . For this reason, the UMBRELLA protocol recommends stratifying patients to either vincristine and actinomycin D plus doxorubicin with a cumulative doxo rubicin dose of 150 mg/m 2 , vincristine, and actinomycin D plus doxorubicin with cumulative doxorubicin of 250 mg/m 2 , or a four-drug regimen including etoposide (150 mg/m 2 /day), carboplatin (200 mg/m 2 /day), cyclophosphamide (450 mg/m 2 /day), and doxorubicin (cumulative dose 300 mg/m 2 ).…”

Seltene Tumordispositionssyndrome mit Manifestation im Kindesalter

“…Dies kann auf ein TDS hinweisen [6]. Die therapeutische Stratifizierung basiert auf der Einteilung in Risikogruppen, die in Abhängigkeit vom Studienprotokoll auf einer Auswahl aus folgenden Faktoren beruht: Alter bei Diagnosestellung, Tumorgröße/-volumen, Histologie, Ansprechen auf Chemotherapie und molekulargenetische Marker (zum Beispiel "loss of heterozygosity" in 1p und 16q) [5,7,8]. Neben der möglichst vollständigen operativen Tumorresektion werden Chemotherapie und Strahlentherapie eingesetzt.…”

Results of the First Prospective Multi-institutional Treatment Study in Children With Bilateral Wilms Tumor (AREN0534) A Report From the Children's Oncology Group

“…[1][2][3][4] However, patients with bilateral Wilms tumor (BWT) have significantly poorer results. On National Wilms Tumor Study 5 (NWTS-5), the four-year EFS estimates for all patients with BWT was 56% (95% CI: 44.8% -66.6%); for patients with favorable histology, focal anaplastic and diffuse anaplastic BWT, four-year estimates were 65% (with retention of heterozygosity at 1p), 76% and 25%, respectively.…”