Implementing Data on Targeted Therapy from the INFORM Registry Platform for Children with Relapsed Cancer in Sweden

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Feb 15

PMID 38357207

Authors

Sofia Wallin

Ingrid Ora

Gabriela Prochazka

Johanna Sandgren

Caroline Bjorklund

Gustaf Ljungman

Hartmut Vogt

Torben Ek

Cornelis M van Tilburg

Anna Nilsson

Affiliations

Soon will be listed here.

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.

References

Marshall M, Ivanovich J, Schmitt M, Helvie A, Langsford L, Casterline J . Pediatric precision oncology: "better three hours too soon than a minute too late". Front Oncol. 2023; 13:1279953. PMC: 10643134. DOI: 10.3389/fonc.2023.1279953. View

Berlanga P, Pierron G, Lacroix L, Chicard M, Adam de Beaumais T, Marchais A . The European MAPPYACTS Trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies. Cancer Discov. 2022; 12(5):1266-1281. PMC: 9394403. DOI: 10.1158/2159-8290.CD-21-1136. View

Grabow D, Kaiser M, Hjorth L, Byrne J, Alessi D, Allodji R . The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries. Eur J Epidemiol. 2018; 33(3):335-349. PMC: 5889790. DOI: 10.1007/s10654-018-0370-3. View

Worst B, van Tilburg C, Balasubramanian G, Fiesel P, Witt R, Freitag A . Next-generation personalised medicine for high-risk paediatric cancer patients - The INFORM pilot study. Eur J Cancer. 2016; 65:91-101. DOI: 10.1016/j.ejca.2016.06.009. View

Rostgaard K, Hjalgrim H, Madanat-Harjuoja L, Johannesen T, Collin S, Hjalgrim L . Survival after cancer in children, adolescents and young adults in the Nordic countries from 1980 to 2013. Br J Cancer. 2019; 121(12):1079-1084. PMC: 6964683. DOI: 10.1038/s41416-019-0632-1. View

Lee J, Gillam L, Visvanathan K, Hansford J, McCarthy M . Clinical Utility of Precision Medicine in Pediatric Oncology: A Systematic Review. JCO Precis Oncol. 2022; 5:1088-1102. DOI: 10.1200/PO.20.00405. View

Stenzinger A, Edsjo A, Ploeger C, Friedman M, Frohling S, Wirta V . Trailblazing precision medicine in Europe: A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany. Semin Cancer Biol. 2021; 84:242-254. DOI: 10.1016/j.semcancer.2021.05.026. View

van Tilburg C, Pfaff E, Pajtler K, Langenberg K, Fiesel P, Jones B . The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets. Cancer Discov. 2021; 11(11):2764-2779. PMC: 9414287. DOI: 10.1158/2159-8290.CD-21-0094. View

Schramm A, Koster J, Assenov Y, Althoff K, Peifer M, Mahlow E . Mutational dynamics between primary and relapse neuroblastomas. Nat Genet. 2015; 47(8):872-7. DOI: 10.1038/ng.3349. View

10.

Vogelstein B, Papadopoulos N, Velculescu V, Zhou S, Diaz Jr L, Kinzler K . Cancer genome landscapes. Science. 2013; 339(6127):1546-58. PMC: 3749880. DOI: 10.1126/science.1235122. View

11.

Edsjo A, Friedman M, Rosenquist R . [Genomic Medicine Sweden - a national initiative for the broad introduction of precision medicine in Swedish healthcare]. Lakartidningen. 2021; 118. View

12.

Pfaff E, El Damaty A, Balasubramanian G, Blattner-Johnson M, Worst B, Stark S . Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience. Eur J Cancer. 2019; 114:27-35. DOI: 10.1016/j.ejca.2019.03.019. View

13.

Langenberg K, Looze E, Molenaar J . The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development. Cancers (Basel). 2021; 13(17). PMC: 8431194. DOI: 10.3390/cancers13174324. View

14.

Wadensten E, Wessman S, Abel F, Diaz De Stahl T, Tesi B, Pietras C . Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer. JCO Precis Oncol. 2023; 7:e2300039. PMC: 10581599. DOI: 10.1200/PO.23.00039. View

15.

Wong M, Mayoh C, Lau L, Khuong-Quang D, Pinese M, Kumar A . Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer. Nat Med. 2020; 26(11):1742-1753. DOI: 10.1038/s41591-020-1072-4. View

16.

Forrest S, Geoerger B, Janeway K . Precision medicine in pediatric oncology. Curr Opin Pediatr. 2017; 30(1):17-24. PMC: 5770114. DOI: 10.1097/MOP.0000000000000570. View

17.

Grobner S, Worst B, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva V . The landscape of genomic alterations across childhood cancers. Nature. 2018; 555(7696):321-327. DOI: 10.1038/nature25480. View

18.

Dupain C, Harttrampf A, Urbinati G, Geoerger B, Massaad-Massade L . Relevance of Fusion Genes in Pediatric Cancers: Toward Precision Medicine. Mol Ther Nucleic Acids. 2017; 6:315-326. PMC: 5363511. DOI: 10.1016/j.omtn.2017.01.005. View

19.

Filbin M, Monje M . Developmental origins and emerging therapeutic opportunities for childhood cancer. Nat Med. 2019; 25(3):367-376. PMC: 6631320. DOI: 10.1038/s41591-019-0383-9. View

20.

Smith L, Stiller C, Aitken J, Hjalgrim L, Johannesen T, Lahteenmaki P . International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries. Int J Cancer. 2021; 150(1):28-37. DOI: 10.1002/ijc.33774. View