Background The last major North American cooperative group clinical trial for relapsed favorable histology Wilms tumor (FHWT) was completed in 2002. The outcomes of patients with relapsed Wilms tumor subsequently treated outside of clinical trials is unknown. The aim of this study was to assess the efficacy and toxicity of salvage therapies used for patients with FHWT suffering first relapse. Methods We conducted a retrospective chart review of patients treated for first relapse of FHWT at six large North American institutions from January 2002 through August 2018. Results Ninety-four patients were identified. Thirty-six patients were classified as standard-risk relapse (SRR), 49 patients as high-risk relapse (HRR) and seven patients as very high-risk relapse (VHRR). Twenty-one patients with SRR were treated with Regimen I. The 4-year EFS and OS for SRR was 82.4% and 93.3%, respectively, with median follow up of 72 months. Twenty-eight HRR/VHRR patients were treated with ICE therapy while 13 received NWTS5 Stratum C. No patient completed protocol therapy per stratum C; median maintenance cycles administered was 2. The 4-year EFS and OS for HRR/VHRR was 32.6% and 58.3%, respectively, with median follow up of 33 months. Conclusions Outcomes for all strata of relapsed WT patients treated in a non-clinical setting appear to have similar outcomes as historical cohorts treated on NWTS5. Improved strategies are urgently needed for HRR and VHRR relapses.

Purpose : To determine whether extent of surgical resection of the primary tumour correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. Methods : Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001-2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumour based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem-cell transplant (SCT). Results : One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete vs. incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p=0.008 and p=0.002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT and surgical resection, only complete resection was associated with statistically significant improved 3 yr EFS and OS, HR=0.48 (0.29-0.81; p=0.006) and HR=0.42 (0.24-0.73; p=0.002). Conclusions : In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.

IntroductionSince the initial attempts to treat children with renal cancer over 50 years ago, outcome for children with renal cancer has generally become promising. While the first endeavors mainly included surgical treatment, in the early 60s radiotherapy and chemotherapy were introduced, leading to cure of patients, including some with metastatic disease. (1) Since then, overall survival rates for the most common type of renal tumors in childhood (nephroblastoma or Wilms tumor) have improved to more than 90 percent. These excellent treatment outcomes are similar in the 2 largest clinical trial groups (the Children’s Oncology Group Renal Tumor Committee (COG-RTC; former National Wilms Tumor Study Group (NTWSG)), and the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG). Despite the difference in upfront treatment choice (primary surgery when feasible (COG-RTC) or preoperative chemotherapy (SIOP-RTSG)) both groups have optimized the stratification of patients in their trials by modifying the intensity of treatment according to individual risk factors, in order to improve outcome for high-risk renal tumor types, but also to reduce early and late toxicity in lower and intermediate risk tumors as much as possible. (2-4)This improvement in risk stratification has resulted in better outcomes and less cancer related toxicity. However, for remaining small subgroups of pediatric renal tumor patients, with very poor outcomes, further understanding of the underlying biology, in correlation with clinic-pathological characteristics, is an unmet need. Further, standard multidisciplinary treatment (surgery, radiotherapy, chemotherapy) can be challenging to access and/or deliver in some low and middle income countries (LMIC). The power inherent in international collaboration to address these challenges was a driving principle that supported the creation of the HARMONICA (HARMONIzation and COllaboration) initiative in 2015, when we established an organized collaborative structure for transatlantic experts from COG-RTC and SIOP-RTSG. The mandate of HARMONICA is to identify specific challenges for pediatric renal tumor subsets in order to meet the aims of our global approach to cure every child with a renal tumor with limited toxicity.The HARMONICA group meets at least once a month by videoconferences, and as much as possible also face to face, at least once or twice a year, during existing pediatric cancer conferences. In addition, several transatlantic HARMONICA expert subgroups are collaborating on specific topics. All work is currently done by a tremendous engagement of many enthusiastic members of both study groups. Despite the fact of obvious advantages, HARMONICA is still lacking funding and needs to optimize their structure as a legal entity. Notwithstanding such limitations, in this special issue of PBC, we present the achievements, the challenges, and the future perspectives, identified by these expert groups.

The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders of erythropoiesis characterized by pathologic deposits of iron in the mitochondria of developing erythroblasts. Mutations in the mitochondrial glycine carrier SLC25A38 cause the most common recessive form of CSA. Nonetheless, the disease is still rare, there being fewer than 70 reported families. Here we describe the clinical phenotype and genotypes of 31 individuals from 24 families, including 11 novel mutations. We also review the spectrum of reported mutations and genotypes associated with the disease, describe the unique localization of missense mutations in transmembrane domains and account for the reoccurrence of several alleles in different populations.