ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001.

BACKGROUND: To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols. METHODS: Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery. RESULTS: 5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors. CONCLUSION: Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.

Prognostic factors for overall survival in paediatric patients with Ewing sarcoma of bone treated according to multidisciplinary protocol.

BACKGROUND: The purpose of this study is to assess the outcome of patients with Ewing sarcoma (EWS) of the bone and to identify prognostic factors. MATERIALS AND METHODS: Seventy-seven patients younger than 18 years old, diagnosed with EWS of the bone between 1979 and 2009, were analysed retrospectively. Four different protocols of chemotherapy were used successively. Local treatment consisted of surgery (N=32), radiotherapy (N=20) and a combination of both (N=19). RESULTS: The median age at diagnosis was 10 years old (range, 2-17) and the median follow-up for survivors 8.6 years (range, 1-18.8). Thirty-two relapses occurred (21 distant, 5 local and 6 both). The 2- and 5-year overall survival rates were 70% and 51%, respectively. Multivariate analysis showed four significant independent predictors for death: age ≥14 years old (HR: 5.06; p=0.019), lack of complete response (HR: 8.04; p<0.001), tumour volume ≥150 ml (HR: 2.21; p=0.045) and distant recurrences (HR: 1.45; p=0.001). CONCLUSIONS: Outcome of EWS of bone is influenced by many clinical and treatment-correlated variables. Criteria to stratify patients should include all the variables that have shown prognostic significance. The development of novel therapies should target these high-risk groups.

Health related quality of life and late side effects of long-term survivors of Ewing's sarcoma of bone.

PURPOSE: The data examining the Health Related Quality of Life (HRQOL) after definitive treatment for Ewing's sarcoma (EWS) is sparse. The objective of this study was to assess the HRQOL and late side effects in EWS of bone survivors treated in the past 2 decades. METHODS: Seventeen long-term (≥ 5 years) EWS survivors (age range, 11-27 years) treated from 1990 to 2004 completed the EORTC-QLQ-C30. We compared the HRQOL of our data set with a reference group of cancer survivors and also with the general population. Musculoskeletal late treatment toxicity was also evaluated. The Mann-Whitney and Wilcoxon tests were used for analyses. RESULTS: EWS survivors of our series reported significantly better global, physical, role and cognitive HRQOL and less symptoms of fatigue, pain and insomnia than the normative sample of cancer survivors. Moreover, the HRQOL was equivalent to the general population, with the exception of social functioning. Additionally, patients with tumor location in the extremities did not report significant HRQOL differences compared with those with tumor at other locations. Common chronic grade 2 side effects were generalized muscle weakness (23%) and decreased joint range of motion (23%). Only one patient experienced musculoskeletal chronic grade 3 toxicity. CONCLUSION: Our findings suggest that EWS survivors treated in the modern era do not experience lower HRQOL than other cancer survivors. Rather, the HRQOL appears to be equivalent to the general population. Further and larger studies are needed to confirm these results.