Effect of radiation after surgery on the prognosis of children with Wilms tumor.

BACKGROUND: To explore the association between radiation after surgery and the 5-year overall survival (OS) and 5-year cancer-specific survival (CSS) in patients with Wilms tumor. METHODS: In this cohort study, 1564 participants were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The univariate and multivariable COX proportional risk model as well as competitive risk model were used to explore the covariates associated with 5-year OS and 5-year CSS of patients with Wilms tumor and the correlation between radiation after surgery and 5-year OS or 5-year CSS of patients with Wilms tumor, respectively. The Kaplan-Meier curves of participants were plotted. RESULTS: The median follow-up was 126.00 (84.00, 178.00) months. Patients receiving surgery had higher 5-year survival probability than those not receiving surgery, while participants receiving radiation after surgery showed poor 5-year survival than those not. After adjusting for covariates including age and SEER stage, increased risk of 5-year overall mortality in patients with Wilms tumor [hazard ratio (HR) = 1.62, 95% confidence interval (CI): 1.10-2.41). After the adjustment for confounding factors including age, SEER stage and ethnicity, increased risk of 5-year cancer-specific mortality of patients with Wilms tumor was observed in those receiving radiation after surgery (HR = 1.77, 95%CI: 1.13-2.79). CONCLUSION: Radiation after surgery was associated with poor prognosis of patients with Wilms tumor, which indicated that the clinicians should assess whether the patient was suitable for using radiation after surgery.

Factors Associated with Outcomes at 1 Year in Paediatric Post-nephrectomy Patients for Nephroblastoma at the University Teaching Hospital and Cancer Diseases Hospital in Lusaka, Zambia.

BACKGROUND: Nephroblastoma is the most common primary malignant renal tumour of childhood. The survival rates in high-income countries are approximately 90%. However, low-income countries have low survival rates of 20%-50%. This study assessed factors associated with treatment outcomes of children post-nephrectomy for nephroblastoma at the University Teaching Hospital and Cancer Diseases Hospital in Lusaka, Zambia. MATERIALS AND METHODS: A retrospective observational cohort study was conducted, where all children diagnosed with unilateral Wilms tumour below the age of 16 years who had nephrectomy from July 2016 to June 2019 were enrolled. Sociodemographic, clinical characteristics and treatment outcomes were noted. All data were coded and stored in a tabular format using Microsoft Excel. Statistical software STATA version 13 was used for analysis. RESULTS: Thirty patients were enrolled. The male-to-female ratio was 1:1. The 1-year event-free survival was 46.7%. Treatment abandonment accounted for 36.6% of the participants. 16.7% of the patients had disease progression. No patient had a relapse or died during the 1-year follow-up period. 66.7% had advanced disease stages III and IV. Advancement in age (above 4.3 years), living in a rural environment more than 100 km away from Lusaka and advanced disease stage were all associated with a poor outcome. CONCLUSIONS: Factors associated with a poor outcome in this study were advanced age and late presentation.

Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa. METHODS: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda. Eligibility criteria were: age younger than 16 years, unilateral WT, diagnosed between 1 January 2021 and 31 December 2022. RESULTS: We included 230 WT patients, median age 3 years, 53% male. Median maximum tumour diameter at diagnosis was 13.6 cm and 33% of patients had metastatic disease. Nephrectomy was performed in 71% of patients, of whom 21% had a tumour rupture. Two-year event-free survival (EFS) was 41.3% ± 3.9% after a median follow-up of 17 months (range: 1-33 months), with treatment abandonment considered an event. Treatment abandonment occurred in 26% and death during treatment in 14%. Disease relapse occurred in 10%. Two-year EFS of the 26 patients who received radiotherapy was 64.5% ± 9.7% with no reported disease relapse. CONCLUSION: Patients continue to present late with advanced WT in sub-Saharan Africa, and their survival is below the 60% GICC target. Prevention of treatment abandonment and treatment-related mortality remain important. Earlier diagnosis and access to radiotherapy are expected to decrease disease-related mortality.

Survival characteristics of Wilms Tumor, a reference developed from a longitudinal cohort study.

BACKGROUND: Wilms tumor (WT) survival has been affected by the evolution in clinical and biological prognostic factors. Significant differences in survival rates indicate the need for further efforts to reduce these disparities. This study aims to evaluate the clinicopathological data impact on survival among patients after Wilm's diagnosis. METHODS: The study utilized the SEERStat Database to identify Wilms tumor patients, applying SEERStat software version 8.3.9.2 for data extraction. Selection criteria involved specific codes based on the International Classification of Diseases for Oncology (ICDO-3), excluding cases with unknown SEER stage, incomplete survival data, unknown size, or lymph node status. Statistical analyses, including Kaplan-Meier estimates and Cox regression models, were conducted using R software version 3.5. Standardized mortality ratios (SMR) were computed with SEER*Stat software, and relative and conditional survival analyses were performed to evaluate long-term survival outcomes. RESULTS: Of 2273 patients diagnosed with Wilms tumor, (1219 patients, 53.6% were females with an average age group of 3-8 years (50.2%). The overall mean survival after five years of diagnosis was 93.6% (2.6-94.7), and the overall mean survival rate was 92.5% (91.3-93.8) after ten years of diagnosis. Renal cancers were identified as the leading cause of death (77.3%), followed by nonrenal cancers (11%) and noncancer causes (11%). Additionally, robust relative survival rates of 98.10%, 92.80%, and 91.3% at one, five, and ten years, respectively, were observed, with corresponding five-year conditional survival rates indicating an increasing likelihood of survival with each additional year post-diagnosis. Univariate Cox regression identified significant prognostic factors: superior CSS for patients below 3 years (cHR 0.48) and poorer CSS for those older than 15 years (cHR 2.72), distant spread (cHR 10.24), regional spread (cHR 3.09), and unknown stage (cHR 4.97). In the multivariate model, age was not a significant predictor, but distant spread (aHR 9.22), regional spread (aHR 2.84), and unknown stage (aHR 4.98) were associated with worse CSS compared to localized tumors. CONCLUSION: This study delving into WT survival dynamics reveals a multifaceted landscape influenced by clinicopathological variables. This comprehensive understanding emphasizes the imperative for ongoing research and personalized interventions to refine survival rates and address nuanced challenges across age, stage, and tumor spread in WT patients.

Elevated preoperative plasma D-dimer level is an independent prognostic factor for pediatric patients with Wilms tumor.

INTRODUCTION: Elevated plasma D-dimer levels are an unfavorable prognostic indicator for various tumors. However, its predictive value for prognosis in pediatric patients with Wilms tumor (WT) remains unknown. We aimed to investigate the clinical and prognostic value of preoperative plasma D-dimer levels and other clinicopathological characteristics in patients with favorable histology WT (FHWT). MATERIALS AND METHODS: The clinical data of 74 children with FHWT from January 2010 to January 2022 were retrospectively analyzed. The clinicopathologic characteristics, preoperative laboratory parameter results, including D-dimer level, and follow-up data were collected. Based on the postoperative recovery status, the patients were divided into tumor-free survival and disease progression groups. The risk factors affecting disease progression in pediatric patients with WT and the impact of plasma D-dimer levels on overall survival (OS) were evaluated. RESULTS: Over a median follow-up of 33 months (range: 2-145 months), 56 patients survived without progression. Relapses and metastases occurred in 18 patients, of which four survived and 14 died. Higher preoperative plasma D-dimer levels (>0.865) (Odds ratio [OR] = 7.240, 95% confidence interval (CI) = 1.276-33.272, P = 0.011) and tumor rupture (OR = 19.984, 95% CI = 1.182-338.013, P = 0.038) were independent prognostic factors for disease progression. Additionally, patients with elevated D-dimer levels demonstrated a worse 5-year OS than those with low D-dimer levels (Hazard ratio (HR) =4.278, 95% CI = 1.074-17.035, P = 0.039). CONCLUSIONS: Elevated D-dimer levels are a prognostic factor for a poorer outcome in pediatric patients with WT and are expected to become a clinical biomarker for predicting the prognosis of WT.

Construction of a Cancer Stem Cell Marker Genes-Related 22-Gene Signature for Overall Survival Prediction in High-Risk Wilms' Tumor.

Background: This study aimed to investigate the comprehensive expression profile of cancer stem cell (CSC)-related genes and construct a prognostic signature for overall survival (OS) prediction in high-risk Wilms' tumor (WT). Materials and methods: Gene expression and survival data from 120 high-risk WT cases in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-WT were used. Results: In total, 229 CSC-related genes were found to be significantly dysregulated in WT compared to tumor-adjacent normal tissues, among which 34 were associated with OS. Using LASSO regression, a 22-gene signature was developed, which exhibited excellent performance in 3-, 5-, and 10-year OS predictions (AUC > 0.86). The high-risk score group showed markedly poorer OS compared to the low-risk score group (median separation, HR = 6.41, 95% CI: 3.18-12.92, p = 3.2e - 9). The 22-gene signature was an independent prognostic factor for OS (HR = 5.086, 95% CI: 3.019-8.568, p < 0.001). Conclusion: This study identified a robust prognostic signature that can effectively support OS prediction.

Bioinformatics Analysis of the Expression and Prognostic Value of PLAU Gene in Wilms' Tumor.

BACKGROUND/AIM: Autophagy and immunity play important roles in the growth of malignant tumors and are promising targets for tumor therapy. This study was conducted to identify differentially expressed immune genes related to autophagy in Wilms' tumor (WT) and analyze their correlation with the disease prognosis. MATERIALS AND METHODS: The public data of WT and normal kidney tissues were downloaded from TCGA, ImmPort, and GeneCards databases to obtain differentially expressed immune genes associated with autophagy. Survival analysis, ROC curve, and clinical relevance filtering were used to screen the key gene plasminogen activator urokinase (PLAU). The univariable and multivariable Cox regression model analyses were used to analyze the prognostic factors of overall survival (OS) in patients with WT. Then, GO enrichment, KEGG pathway analysis and GSEA were used to enrich and analyze differentially expressed genes. The relationship between PLAU gene expression and tumor microenvironment and infiltration of immune cells was analyzed, as well as between the expression of PLAU and epigenetic modifications. RESULTS: PLAU gene expression was associated with survival and prognosis in WT patients and was an independent prognostic indicator of OS in patients. The GO, KEGG, and GSEA analysis results suggested that PLAU may be involved in RNA transcription and epithelial cell migration. High expression of PLAU was also associated with increased immune cell infiltration and a higher presence of antitumor immune cells. The low expression of PLAU in WT was related to DNA methylation and may be also co-regulated by miR-342-3p. CONCLUSION: PLAU can be used as an independent prognostic biomarker for WT. Low expression of PLAU is associated with poor prognosis in WT patients. Evidence on the prognostic value of PLAU gene and the pathways that may be associated with its expression is invaluable for the development of new therapies for WT.

Real-world implementation of North American and SIOP strategies for the treatment of Wilms tumor in Uruguay.

Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

The impact of the route to diagnosis in nephroblastoma.

INTRODUCTION: Wilms tumor (WT) is the most common childhood kidney cancer. It is a rapid growing embryonal tumor in young children and can be diagnosed with and without tumor related symptoms. METHODS: We retrospectively analyzed the route to diagnosis of WT treated prospectively according to the SIOP 93-01/GPOH and 2001/GPOH in Germany between 1993 and 2022. Four routes were defined: diagnosis due to tumor-related symptoms, incidental diagnosis during another disease, diagnosis by preventive examinations, and diagnosis within a surveillance program. For these groups we compared clinical and tumor characteristics and outcome. RESULTS: Of 2549 patients with WT 1822 (71.5%) were diagnosed by tumor-related symptoms, 472 (18.5%) incidentally, 213 (8.4%) by preventive medical examinations, and 42 (1.6%) by surveillance. Age, general health status, tumor volume, and local and overall stage varied significantly between these groups. The youngest patients were those diagnosed by preventive medical examination (mean: 1.70 years). These patients also showed the best general health status. Tumor volume at diagnosis (549 mL) and after preoperative chemotherapy (255 mL) was significantly higher for children with tumor-related symptoms. The highest percentage of local stage I (78.6%) and the lowest percentage of metastatic disease (4.8%) was found in the surveillance group. The outcome of patients was not significantly different, with up to 19.0% relapses in the surveillance group and 3.0% deaths in the group with tumor-related symptoms. CONCLUSION: The route to diagnosis of WT correlates with age, general health status, tumor volume, and stage distribution, but does not impact the outcome of patients. Nonetheless, diagnosis without tumor related symptoms results in lower treatment burden and thus improved quality of life.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Current Realities of Wilms Tumor Burden and Therapy in Ghana.

BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.

Nomogram for personalized prognostic assessment of children with favorable histology Wilms tumor: A retrospective analysis.

OBJECTIVE: This retrospective study aimed to construct and validate a nomogram for personalized prognostic assessment of favorable histology Wilms tumor (FHWT) based on clinical and pathological variables. METHODS AND MATERIALS: This was a retrospective study collected data from patients who underwent surgery for FHWT between March 2007 and November 2022 at Beijing Children's Hospital. Univariate and multivariate Cox proportional hazards regression analyses were conducted to determine the significance variables and constructed the nomogram in predicting event-free survival (EFS) in FHWT patients. RESULTS: A total of 401 FHWT patients were included in the study, with the median age of the patients was 3.4 years. The overall 1-, 3-, and 5-year OS rates were 98.2%, 96.3%, and 93.9%. The 1-, 3-, and 5-year EFS rates were 91.2%, 88.2%, and 86.6%. Subgroup analysis revealed age greater than 2 years was associated with a worse prognosis than age less than or equal to 2 years (P < 0.001), and patients with high-risk Wilms tumors were associated with a higher rate of recurrence and death (P < 0.001). Multivariate analysis showed that age (HR: 2.449, 95%CI: 1.004-5.973), stage (HR: 1.970, 95% CI:1.408-2.756), and histological risk (HR:9.414, 95% CI: 4.318-20.525) were identified as independent predictors of EFS (P < 0.05) and used to construct the nomogram. The prognostic nomogram demonstrated good calibration, great clinical utility, and the time-dependent receiver operating curve analysis showed that the nomogram had precise predictability, with area under the curve values of 0.85(95CI:0.796-0.913), 0.85(95CI:0.80-0.91), and 0.88(95CI:0.839-0.937) for 1-,3-year and 5-year EFS. CONCLUSION: This study provides valuable insights into the clinical characteristics and outcomes of FHWT patients. Accurate staging and histological risk assessment are important in predicting outcomes, and the prognostic nomogram we developed can be a useful tool for clinicians to assess patient prognosis and make informed treatment decisions.

The role of liver resection in metastatic nephroblastoma: a systematic review and Meta-regression analysis.

BACKGROUND: The impact of hepatic resection for liver metastases (LM) on the survival of pediatric patients with Wilms' tumor (WT) is unclear. So far, there is a lack of studies investigating the best suited treatment for patients with WTLM, and the role of liver resection has rarely been investigated. Thus, the development of evidence-based guidelines concerning indications of liver resection for WTLM remains difficult. AIM: To investigate the role of surgery in the therapy of WTLM. All available data on liver resections and subgroup outcomes of patients with WTLM are analyzed. Main research question is whether liver resection improves survival rates of patients with WTLM compared to non-surgical treatment. METHODS: A systematic literature search of MEDLINE, Web of Science, and Central provided the basis for this PRISMA-compliant systematic review. For the main analysis (I), all studies reporting on surgical treatment of pediatric WTLM were included. To provide a representative overview of the general outcome of WTLM patients, in analysis II all studies with cohorts of at least five WTLM patients, regardless of the kind of treatment, were reviewed and analyzed. A Multiple meta-regression model was applied to investigate the impact liver resection on overall survival. RESULTS: 14 studies with reports of liver resection for WTLM were found (Analysis I). They included a total of 212 patients with WTLM, of which 93 underwent a liver resection. Most studies had a high risk of bias, and the quality was heterogenous. For the analysis II, eight studies with subgroups of at least five WTLM patients were found. The weighted mean overall survival (OS) of WTLM patients across the studies was 55% (SD 29). A higher rate of liver resection was a significant predictor of better OS in a multiple meta-regression model with 4 covariates (I2 29.43, coefficient 0.819, p = 0.038). CONCLUSIONS: This is the first systematic review on WTLM. Given a lack of suited studies that specifically investigated WTLM, ecological bias was high in our analyses. Generating evidence is complicated in rare pediatric conditions and this study must be viewed in this context. Meta-regression analyses suggest that liver resection may improve survival of patients with WTLM compared to non-surgical treatment. Especially patients with persisting disease after neoadjuvant chemotherapy but also patients with metachronous LM seem to benefit from resection. Complete resection of LM is vital to achieve higher OS. Studies that prospectively investigate the impact of surgery on survival compared to non-surgical treatment for WTLM are highly needed to further close the current evidence gap. STUDY REGISTRATION: PROSPERO 2021 CRD42021249763  https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249763 .

Somatic-type Malignancies in Testicular Germ Cell Tumors: A Clinicopathologic Study of 63 Cases.

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.

Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome.

BACKGROUND: Renal cancer is a common malignant tumor with an increasing incidence rate. METHODS: In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. RESULTS: After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion, the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome. CONCLUSIONS: Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.

[Impact of an early diagnosis program for childhood cancer in Abidjan?] / Impact d'un programme de diagnostic précoce des cancers de l'enfant à Abidjan ?

INTRODUCTION: To promote the early diagnosis of pediatric cancers in Ivory Coast, we have initiated a program to train local physicians in the warning signs and to raise public awareness. The aim of this work was to compare the times, stages and survival of patients before and three years after the initiation of the program. METHODS: This retrospective study involved children 0-17 years of age admitted from January to December 2014 and from May 2018 to April 2019. The Mann-Whitney non-parametric test and the Fisher's exact test were used to compare time limits, stages and survival. RESULTS: One hundred and fifty-nine doctors were trained and 1020 people were sensitized. The median age of the 216 children included was 7 years, sex ratio 1.4. For both periods, the median consultation times were 75 and 30 days (P=0.003) and the median diagnostic times were 120 and 105 days (P=0.033). High-risk lymphomas accounted for 60.5% and 58.5% (P=0.99) respectively and nephroblastoma 46.1% and 56.2% (P=0.51). The overall survival was 31% and 30.2% (P=0.92). DISCUSSION: The early diagnosis program had no impact. The diagnosis times and the proportion of cancer classified as high risk are comparable to the data reported in sub-Saharan Africa, which vary respectively from 7 to 15.8 weeks and from 60 to 71%. This program must be intensified, extended to all health workers and include improving access to care.

Stage at diagnosis and survival by stage for the leading childhood cancers in three populations of sub-Saharan Africa.

The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. In our study, data from three population-based registries in sub-Saharan Africa (Abidjan, Harare and Kampala) were examined for children aged under 15. We assessed the feasibility of assigning stage at diagnosis according to Tier 1 of the Toronto Childhood Cancer Stage Guidelines for patients with non-Hodgkin lymphoma [including Burkitt lymphoma (BL)], retinoblastoma and Wilms' tumour. Patients were actively followed-up, allowing calculation of 3-year relative survival by cancer type and registry. Stage-specific observed survival was estimated. The cohort comprised 381 children, of whom half (n = 192, 50%) died from any cause within 3 years of diagnosis. Three-year relative survival varied by malignancy and location and ranged from 17% [95% confidence interval (CI) = 6%-33%] for BL in Harare to 57% (95% CI = 31%-76%) for retinoblastoma in Kampala. Stage was assigned for 83% of patients (n = 317 of 381), with over half having metastatic or advanced disease at diagnosis (n = 166, 52%). Stage was a strong predictor of survival for each malignancy; for example, 3-year observed survival was 88% (95% CI = 68%-96%) and 13% (4%-29%) for localised and advanced BL, respectively (P < .001). These are the first data on stage distribution and stage-specific survival for childhood cancers in Africa. They demonstrate the feasibility of the Toronto Stage Guidelines in a low-resource setting and highlight the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.

Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse.

Whereas 90% of patients with Wilms tumor (WT) reach cure, approximately half of patients developing a recurrent tumor die of the disease. Therefore, to disclose events leading to recurrence represents a clinical need. To study paired primary/recurrent tumor samples, being aware of the intra-tumoral heterogeneity, might help finding these answers. We previously suggested that mutations in SIX1 and DROSHA underlie WT recurrence. With the aim to better investigate this scenario, we collected 19 paired primary/recurrent tumors and 10 primary tumors from relapsing patients and searched for mutations in the SIX1/2 genes and microRNA processing genes (miRNAPGs). We found SIX1 mutation in one case, miRNAPGs mutations in seven cases, and the co-occurrence of SIX1 and miRNAPG mutations in one case. We could observe that, whereas in primary tumors the mutations could be heterogeneously present, in all cases they were positively selected and homogeneously present in the recurrent disease, as also indicated by a "moderate" and "almost perfect" agreement (according to the Landis and Koch classification criteria) between paired samples. Analysis of SIX1/2 genes and miRNAPGs in 50 non-relapsing WTs disclosed SIX2 mutation in one case and miRNAPGs mutations in seven. A borderline statistically significant association was observed between miRNAPGs mutations and the occurrence of relapse (p value: 0.05). These data suggest that SIX1 and miRNAPGs mutations may provide an advantage during tumor progression to recurrence and can represent oncogenic drivers in WT development.

CD8+ T-cell lymphocytes infiltration predict clinical outcomes in Wilms' tumor.

The abundance and location of CD8+ tumor-infiltrating lymphocytes demonstrate important facets of the anticancer immune response. CD8-expressing lymphocytes have been used in immunotherapy for multiple cancers. This study aims to determine the association between the abundance and localization of CD8+ tumor-infiltrating lymphocytes and clinical outcomes of Wilms' tumor. This retrospective study employed 42 pediatric patients diagnosed with Wilms' tumor. CD8+ tumor-infiltrating lymphocyte counts were calculated based on the mean percentage of stroma occupied by CD8+ lymphocytes at the center and the invasive border of the tumor using immunohistochemistry. CD8+ tumor-infiltrating lymphocyte counts were significantly higher in the center and the invasive border of the early-stage tumor samples. CD8+ tumor-infiltrating lymphocytes in the invasive border and tumor center positively correlated with tumor invasion, regional lymph node invasion, histological type, metastasis, and stage of the tumor. A high CD8+ tumor-infiltrating lymphocyte scores at the invasive margin of the tumor correlated with low tumor recurrence. Low CD8+ tumor-infiltrating lymphocyte scores in the two tumor regions correlated with poor prognosis and shorter disease-free survival. Overall, these findings show that patients with high CD8+ tumor-infiltrating lymphocytes are associated with better clinical outcomes. Therefore, measuring the abundance of CD8+ tumor-infiltrating lymphocytes may be useful in predicting response to cancer immunotherapies.