Implementing data on targeted therapy from the INFORM registry platform for children with relapsed cancer in Sweden

Sofia Wallin; Ingrid Øra; Gabriela Prochazka; Johanna Sandgren; Caroline Björklund; Gustaf Ljungman; Hartmut Vogt; Torben Ek; Cornelis M van Tilburg; Anna Nilsson

doi:10.3389/fonc.2024.1340099

Implementing data on targeted therapy from the INFORM registry platform for children with relapsed cancer in Sweden

Front Oncol. 2024 Jan 31:14:1340099. doi: 10.3389/fonc.2024.1340099. eCollection 2024.

Authors

Sofia Wallin¹, Ingrid Øra², Gabriela Prochazka³, Johanna Sandgren^{3

4}, Caroline Björklund⁵, Gustaf Ljungman⁶, Hartmut Vogt⁷, Torben Ek⁸, Cornelis M van Tilburg^{9

10

11

12}, Anna Nilsson^{1

13}

Affiliations

¹ Division of Pediatric Oncology, Department of Women and Children´s Health, Karolinska Institutet, Stockholm, Sweden.
² Division of Pediatric Hematology-Oncology, Skåne University Hospital, & Clinical Sciences IKVL, Lund University, Lund, Sweden.
³ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
⁴ Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
⁵ Division of Pediatric Hematology-Oncology, Umeå University Hospital, Umeå, Sweden.
⁶ Department of Women and Children´s Health, Pediatric Hematology-Oncology Uppsala University, Uppsala, Sweden.
⁷ Division of Pediatric Hematology-Oncology B153, Crown Princess Victoria Children's Hospital, and Division of Children's and Women's Health, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
⁸ University of Gothenburg and Children´s Cancer Center, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁹ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
¹⁰ Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹¹ Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.
¹² German Cancer Consortium (DKTK), National Center for Tumor diseases (NCT), Heidelberg, Germany.
¹³ Division of Pediatric Hematology-Oncology, Tema Barn, Astrid Lindgren Children's Hospital, Stockholm, Sweden.

Abstract

Background: Advances in treatment of childhood malignancies have improved overall cure rates to 80%. Nevertheless, cancer is still the most common cause of childhood mortality in Sweden. The prognosis is particularly poor for relapse of high-risk malignancies. In the international INFORM registry, tumor tissue from patients with relapsed, refractory, or progressive pediatric cancer as well as from very-high risk primary tumors is biologically characterized using next-generation sequencing to identify possible therapeutic targets. We analyzed data from Swedish children included in the INFORM registry concerning patient characteristics, survival, sequencing results and whether targeted treatment was administered to the children based on the molecular findings.

Methods: A registry-based descriptive analysis of 184 patients included in the INFORM registry in Sweden during 2016-2021.

Results: The most common diagnoses were soft tissue and bone sarcomas followed by high grade gliomas [including diffuse intrinsic pontine glioma (DIPG)]. Complete molecular analysis was successful for 203/212 samples originating from 184 patients. In 88% of the samples, at least one actionable target was identified. Highly prioritized targets, according to a preset scale, were identified in 48 (24%) samples from 40 patients and 24 of these patients received matched targeted treatment but only six children within a clinical trial. No statistically significant benefit in terms of overall survival or progression free survival was observed between children treated with matched targeted treatment compared to all others.

Conclusion: This international collaborative study demonstrate feasibility regarding sequencing of pediatric high-risk tumors providing molecular data regarding potential actionable targets to clinicians. For a few individuals the INFORM analysis was of utmost importance and should be regarded as a new standard of care with the potential to guide targeted therapy.

Keywords: molecular diagnostic techniques; molecular targeted therapy; pediatric cancer; pediatric oncology; precision medicine.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We are grateful for the financial support from the Swedish Childhood Cancer Fund (BCF), Entrepreneurs for good and ARMEC Lindeberg Foundation directed to inclusion and follow up of children in Sweden included in the Inform registry. The INFORM program is financially supported by the German Cancer Research Center (DKFZ), the German Cancer Consortium (DKTK), the German Federal Ministry of Education and Research (BMBF), the German Federal Ministry of Health (BMG), the Ministry of Science, Research and the Arts of the State of Baden-Württemberg (MWK BW); the German Cancer Aid (DKH), the German Childhood Cancer Foundation (DKS), RTL television, the aid organization BILD hilft e.V. (Ein Herz für Kinder) and the generous private donation of the Scheu family.