The group of Childhood Cancer and Blood Disorders of the Vall d'Hebron Research Institute (VHIR) and the Pediatric Oncology and Hematology Department of the Vall d'Hebron University Hospital have participated in a European clinical trial that has allowed the sequencing of tumours in patients with recurrent paediatric cancer with the aim of facilitating access to targeted therapies. The results of the work, led by the Gustave Roussy Cancer Institute (France), have been published in Cancer Discovery.

Cancer is the leading cause of disease-related death in children and adolescents. It is a pathology that can have very different molecular characteristics among patients depending on the alterations that the tumor presents. "Identifying these alterations is key to improving access to targeted therapies for pediatric patients with recurrent or refractory cancer. The ultimate goal is to increase their treatment options", explains Dr. Raquel Hladun, pediatric oncologist at the Pediatric Oncology and Hematology Service of Vall d'Hebron University Hospital and researcher of the Childhood Cancer and Blood Disorders group at VHIR. This is the aim of the MAPPYACTS study ("Stratification of molecular profiles in the treatment of pediatric and juvenile cancer"), developed between 2016 and 2020 with 787 children, adolescents and young adults with different types of relapsed or refractory cancer to therapy from 18 centers in France, Italy, Ireland and Spain. Vall d'Hebron was the only center in Spain to participate.

To carry out the study, tumor samples were obtained through biopsies, which were extracted specifically for the work to ensure that they were as recent as possible. The researchers then carried out tumor sequencing to study genetic alterations. Based on this, a specific treatment, if available, was recommended for each patient's particular alteration. The study thus facilitated patient access to ready-to-use therapies or to clinical trials of new treatments.

In the analysis of the samples, at least one genetic alteration associated with a recommendation for targeted therapies was identified in 436 patients (69%), of whom 10% had a recommendation for a targeted therapy approved for clinical use. Among the 365 patients with a follow-up of more than 12 months, 30% received one or more targeted therapies, most through early-stage clinical trials targeting the pediatric population such as the AcSé-ESMART trial. Patients with a targeted therapy had a 17% objective response rate, i.e. in these cases the tumor was reduced after treatment. This figure increased to 38% in cases where the drug was already approved for use.

Finally, MAPPYACTS was the first project to study the use of liquid biopsy to analyze circulating DNA in blood in this population. Thus, it was found that 76% of the alterations detected in extra-cerebral tumors could also be detected in circulating DNA in blood by liquid biopsy. This methodology, which will be studied in depth in future studies, is a less invasive technique than the standard biopsy that enables analysis of heterogeneity within the same tumor, better monitoring of the response to treatment or anticipation of the appearance of relapses.

"Participating in international precision medicine trials such as MAPPYACTS allows us to consolidate the collaboration network with other centers in Europe. It is very important in the case of childhood cancers because they are considered minority diseases and we need to work collaboratively to advance in the improvement of their treatments. The MAPPYACTS study has also allowed us to grow our own personalized medicine program at Vall d'Hebron", says Dr. Aroa Soriano, principal investigator of the Childhood Cancer and Blood Disorders group at VHIR. In this sense, Vall d'Hebron promotes the Comik program of personalized medicine in pediatric solid tumors since 2016. In the coming months, it will launch the PENCIL-SEHOP project for the implementation of personalized medicine programs to which pediatric patients from all over Spain can access.

The study has been possible thanks to the collaboration of a large number of professionals from Pediatric Oncology, Pediatric Surgery, Pediatric Pathology, Pediatric Radiology, Molecular Biology, Translational Research and Bioinformatics of the Vall d'Hebron Campus. The analyses performed at the Centro Nacional de Análisis Genómico have been possible thanks to the support of the FERO Foundation, the Rotary Clubs of Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg and Deutschland Gemeindienst e.V., among others, and the support of Vall d'Hebron families.