Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

[Renal tumors in children and adolescents]. / Nierentumoren bei Kindern und Jugendlichen.

CLINICAL/METHODOLOGICAL ISSUE: Diagnosis and therapy of renal tumors in children and adolescents are standardized by study protocols from major international societies. Imaging plays a central role, and in Europe patients between the ages of 6 months and 14 years with renal tumors are referred to neoadjuvant chemotherapy without histological confirmation according to the study protocol due to the frequency of Wilms tumor. STANDARD RADIOLOGIC METHODS: Ultrasound is used worldwide as the primary investigative procedure for suspected renal tumors. In Europe, magnetic resonance imaging (MRI) has become established for more advanced diagnosis. In addition to differential diagnosis, staging is crucial for therapy. According to current protocol, this includes computed tomography (CT) of the thorax for the evaluation of pulmonary metastases. METHODOLOGICAL INNOVATIONS: Diffusion-weighted MRI provides promising results for the differentiation of nephroblastoma subtypes in addition to improved detectability of tumor foci. However, sufficient evidence is lacking. PERFORMANCE: Differentiation of Wilms tumor from the highly malignant non-Wilm tumors, such as malignant rhabdoid tumor and clear cell sarcoma of the kidney, remains inconclusive based on imaging alone. Differential diagnosis is, therefore, based on morphologic and epidemiologic criteria. ASSESSMENT: The high degree of standardization in the diagnosis and treatment of renal tumors in children and adolescents has led to a significant improvement in prognosis. Overall survival of patients with Wilms tumor is currently over 90%.

Hallmark discoveries in the biology of Wilms tumour.

The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the 'two-hit' model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics - from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.

Disseminated adult Wilms tumor in pregnancy: Leveraging multidisciplinary care in a low-resource setting.

Wilms tumor (WT) occurring in adults is rare and even much more rarely found to coexist with pregnancy. Clinical outcome in adults is worse overall compared with pediatric patients with WT and is often misdiagnosed with no standardized protocols for care guided by high-evidence clinical trials. We present a case of a 23-year-old woman diagnosed with WT who was found to be pregnant immediately following nephrectomy. Workup findings showed that she had disseminated disease but was successfully managed in a multidisciplinary team setting with modified intrapartum chemotherapy followed by postpartum chemotherapy. In low-resource settings, management protocols for adult patients with WT can be individualized by multidisciplinary teams to leverage available resources for best outcomes.

Wilms' tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives.

This mini-review explores recent advancements in cancer vaccines that target Wilms' tumor (WT1). Phase I/II trials of WT1 peptide vaccines have demonstrated their safety and efficacy against various cancers. Early trials employing HLA class I peptides evolved through their combination with HLA class II peptides, resulting in improved clinical outcomes. Additionally, WT1-targeted dendritic cell vaccines have exhibited favorable results. Studies focusing on hematological malignancies have revealed promising outcomes, including long-term remission and extended survival times. The combination of vaccines with immune checkpoint inhibitors has shown synergistic effects. Current preclinical developments are focused on enhancing the effectiveness of WT1 vaccines, underscoring the necessity for future large-scale Phase III trials to further elucidate their efficacy.

Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.

Bilateral Wilms tumor in a patient with a horseshoe and duplex kidney: A case report.

The occurrence of horseshoe kidney with duplex urinary collecting systems is rare. Herein, we report a case of bilateral Wilms tumor (BWT) in a patient with a concurrent horseshoe kidney and left duplex kidney, which had not been previously reported. The patient was treated with neoadjuvant chemotherapy, followed by surgical resection and adjuvant chemotherapy. The tumor recurred 6 months postoperatively. A second resection was performed, followed by the administration of chemotherapy and radiotherapy. The patient passed away 15 months after the initial diagnosis of BWT.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Using Crowdfunding Campaigns to Examine Financial Toxicity and Logistical Burdens Facing Families of Children With Wilms Tumor.

INTRODUCTION: Treatment for pediatric solid tumors is often intense and multidisciplinary and can create a substantial financial burden for families. Assessing these burdens, termed the financial toxicity of treatment, can be difficult. Using Wilms tumor as an example, we evaluated crowdfunding campaigns in an attempt to better understand the impact of economic and logistic challenges associated with pediatric solid tumor care and identify features associated with successful fundraising with this method. METHODS: We used a webscraping algorithm to identify crowdfunding campaigns on GoFundMe.com for pediatric patients with Wilms tumor in the United States. We conducted a cross-sectional analysis to describe the patients and families seeking crowdfunding support for cancer care. After fundraizing information was extracted using the webscraping algorithm, each fundraiser was verified and examined by two independent reviewers to assess demographic, qualitative, disease, and treatment variables. Successful fundraisers, defined as those meeting stated financial goals, were compared to unsuccessful campaigns to identify variables associated with successful crowdfunding campaigns. RESULTS: We identified 603 children with Wilms tumor and an associated crowdfunding campaign. The median age was 4 y. The majority lived in two-parent households (68.5%). Patients mentioned siblings in 35.5% of fundraisers. While motivations for crowdfunding varied, hardships endured by families included loss of employment (52.2%), need for childcare for other children (9.8%), direct costs of care [co-payments, insurance, pharmaceuticals, out-of-pocket care costs, etc.] (80.9%), indirect costs associated with seeking care [transportation, parking, lodging, lost opportunity cost, etc.] (56.2%), and need for relocation to pursue complex cancer care (6.8%). Disease characteristics in this cohort were limited to self-reports by families. However, fundraisers mentioned disease characteristics, including tumor stage (47.6%), size (11.4%), positive nodal status (9.6%), metastatic disease (3.6%), pathology (11.8%), upstaging (4.6%), and disease recurrence (8.6%). No individually examined demographic, support, disease, or hardship-related factors varied significantly between successful and unsuccessful crowdfunding campaigns (all P > 0.05). However, successful campaigns requested less money ($11,783.25 successful versus $22,442.2 unsuccessful, <0.001), received more money ($16,409.5 successful vs 7427.4 unsuccessful, P < 0.001), and solicited larger donor numbers (170.3 successful versus 86.3 unsuccessful, P < 0.001). CONCLUSIONS: Families whose children undergo multimodal cancer care have significant expenses and burdens and can use crowdfunding to support their costs. Careful consideration of the financial and logistic strains associated with pediatric solid tumor treatment, including thorough analysis of crowdfunding sites, may support better understanding of nonclinical burdens, supporting therapeutic relationships and patient outcomes.

Wilms Tumor.

Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal tumor of childhood. It is an embryonal tumor that develops from remnants of immature kidney. There are approximately 500 new WT cases diagnosed in the United States every year. Advances in multimodal therapy including surgery, chemotherapy, and radiation therapy given according to risk stratification have allowed most patients to achieve survival rates in excess of 90%.

One year overall survival of wilms tumor cases and its predictors, among children diagnosed at a teaching hospital in South Western Uganda: a retrospective cohort study.

BACKGROUND: Wilms tumor (WT) is the second most common solid tumor in Africa with both low overall survival (OS) and event-free survival (EFS) rates. However, no known factors are predicting this poor overall survival. OBJECTIVE: The study was to determine the one-year overall survival of WT cases and its predictors among children diagnosed in the pediatric oncology and surgical units of Mbarara regional referral hospital (MRRH), western Uganda. METHODOLOGY: Children's treatment charts and files diagnosed and managed for WT were retrospectively followed up for the period between January 2017 to January 2021. Charts of children with histologically confirmed diagnoses were reviewed for demographics, clinical and histological characteristics, as well as treatment modalities. RESULTS: One-year overall survival was found to be 59.3% (95% CI: 40.7-73.3), with tumor size greater than 15 cm (p 0.021) and unfavorable WT type (p 0.012) being the predominant predictors. CONCLUSION: Overall survival (OS) of WT at MRRH was found to be 59.3%, and predictive factors noted were unfavorable histology and tumor size greater than 115 cm.

Outcomes according to treatment using an established protocol in patients with bilateral Wilms' tumor: A national Canadian population-based study.

BACKGROUND: Bilateral Wilms tumor (BWT) is a rare entity. The goal of this study is to report outcomes (overall and event-free survival, OS/EFS) of BWT in a large cohort representative of the Canadian population since 2000. We focused on the occurrence of late events (relapse or death beyond 18 months), as well as outcomes of patients treated following the only protocol specifically designed for BWT to date, AREN0534, compared to patients treated following other therapeutic schemes. METHODS: Data was obtained for patients diagnosed with BWT between 2001 and 2018 from the Cancer in Young People in Canada (CYP-C) database. Demographics, treatment protocols, and dates for events were collected. Specifically, we examined outcomes of patients treated according to the Children's Oncology Group (COG) protocol AREN0534 since 2009. Survival analysis was performed. RESULTS: 57/816 (7%) of patients with Wilms tumor had BWT during the study period. Median age at diagnosis was 2.74 years (IQR 1.37-4.48) and 35 (64%) were female; 8/57 (15%) had metastatic disease. After a median follow-up of 4.8 years (IQR 2.8-5.7 years, range 0.2-18 years), OS and EFS were 86% (CI 73-93%) and 80% (CI 66-89%), respectively. Less than 5 events were recorded after 18 months from diagnosis. Since 2009, patients treated according to the AREN0534 protocol had a statistically significant higher OS compared to patients treated with other protocols. CONCLUSIONS: In this large Canadian cohort of patients with BWT, OS and EFS compared favorably to the published literature. Late events were rare. Patients treated according to a disease-specific protocol (AREN0534) had improved overall survival. TYPE OF STUDY: Original article. LEVEL OF EVIDENCE: Level IV.

Development and Validation of a Prediction Model for Kidney Failure in Long-Term Survivors of Childhood Cancer.

PURPOSE: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer. METHODS: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a comparator. Piecewise exponential models accounting for race/ethnicity, age at diagnosis, nephrectomy, chemotherapy, radiotherapy, congenital genitourinary anomalies, and early-onset hypertension estimated the relationships between potential predictors and kidney failure, using area under the curve (AUC) and concordance (C) statistic to evaluate predictive power. Regression coefficient estimates were converted to integer risk scores. The St Jude Lifetime Cohort Study and the National Wilms Tumor Study served as validation cohorts. RESULTS: Among CCSS survivors, 204 developed late kidney failure. Prediction models achieved an AUC of 0.65-0.67 and a C-statistic of 0.68-0.69 for kidney failure by age 40 years. Validation cohort AUC and C-statistics were 0.88/0.88 for the St Jude Lifetime Cohort Study (n = 8) and 0.67/0.64 for the National Wilms Tumor Study (n = 91). Risk scores were collapsed to form statistically distinct low- (n = 17,762), moderate- (n = 3,784), and high-risk (n = 716) groups, corresponding to cumulative incidences in CCSS of kidney failure by age 40 years of 0.6% (95% CI, 0.4 to 0.7), 2.1% (95% CI, 1.5 to 2.9), and 7.5% (95% CI, 4.3 to 11.6), respectively, compared with 0.2% (95% CI, 0.1 to 0.5) among siblings. CONCLUSION: Prediction models accurately identify childhood cancer survivors at low, moderate, and high risk for late kidney failure and may inform screening and interventional strategies.

Renal Yolk Sac Tumor Clinically Misdiagnosed as Nephroblastoma: A Case Report.

Background: Yolk sac tumor is a germ cell tumor (GCT) that occurs in infants and adolescents and affects various sites. There is a trend to treat pediatric renal tumors before a tissue diagnosis. We report a renal yolk sac tumor clinically misdiagnosed as Wilms tumor, based on ultrasound (US) and MRI.Case Report: This 21-month-old male infant was discovered to have a space occupying lesion in the right kidney. Because the tumor was large, initial radiotherapy preceded surgical resection. Histologically, the tumor was a yolk sac tumor.Conclusion: Imaging examination of renal yolk sac tumor can easily be misdiagnosed as Wilms tumor. SIOP treatment plan for Wilms tumor requires preoperative chemotherapy, which is different from the treatment regimen for yolk sac tumor. Preoperative alpha-fetoprotein could have been helpful in avoiding this clinical misdiagnosis.

Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study.

PURPOSE: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens. METHODS: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents. RESULTS: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity. CONCLUSION: With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.

Imaging of pediatric renal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper focused on Wilms tumor and nephrogenic rests.

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.

Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges.

Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies. These therapies have improved event-free and overall survival for children. However, several challenges remain and not all children have benefited from the improved outcomes. In this article, we review the global epidemiology of pediatric renal tumors, including key consortium and global studies. We identify current knowledge gaps and challenges facing both high and low middle-incomes countries.

[Epidemiological and clinical profile childhood cancers with pleural and pulmonary lesions in the pediatric oncology unit of Treichville University Hospital (Abidjan, Côte d'Ivoire)]. / Profil épidémiologique et clinique des cancers pédiatriques avec atteintes pleurales et pulmonaires au service de pédiatrie du CHU de Treichville (Abidjan, Côte d'Ivoire).

INTRODUCTION: Pediatric cancers are a major public health problem in sub-Saharan Africa. However, they are seldom studied, especially as regards in their extensive forms. METHODOLOGY: An eight-year retrospective and descriptive study was carried out so as to specify the epidemiological and clinical characteristics of cancers with pleural and pulmonary involvement in children of 0 to 14years of age in the pediatric oncology unit at the University Hospital of Treichville, Côte d'Ivoire (Ivory Coast). RESULTS: The frequency of pleural and pulmonary involvement in pediatric cancers was 13.8%. Children's average age was 7.2years, with sex ratio at 2.11. Solid tumors were predominant, with a predominance of Burkitt's lymphoma (39.3%) and nephroblastoma (35.7%). The most affected age groups were 10 to 15years (Burkitt's lymphoma) and 0 to 5years (nephroblastoma). Time to diagnosis ranged from 31 and 60days in 40.4% of cases, and time to treatment was at most 30 days, for the overwhelming majority (97.1%) of the children. Chemotherapy was initiated in 67.9% of patients. Hospital mortality was 73.2%. CONCLUSION: Through this study, the authors established the profile of childhood cancers with pleural and pulmonary involvement. Comparative studies of mortality in pediatric cancers with and without pleural and pulmonary involvement could further underline the importance of early management before dissemination.