Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement

Author:

Green Darrell1ORCID,van Ewijk Roelof2ORCID,Tirtei Elisa34ORCID,Andreou Dimosthenis5ORCID,Baecklund Fredrik6ORCID,Baumhoer Daniel7ORCID,Bielack Stefan S.8ORCID,Botchu Rajesh9ORCID,Boye Kjetil10ORCID,Brennan Bernadette11ORCID,Capra Michael12ORCID,Cottone Lucia13ORCID,Dirksen Uta14ORCID,Fagioli Franca34ORCID,Fernandez Natalia15ORCID,Flanagan Adrienne M.1316ORCID,Gambarotti Marco17ORCID,Gaspar Nathalie1819ORCID,Gelderblom Hans20ORCID,Gerrand Craig21ORCID,Gomez-Mascard Anne2223ORCID,Hardes Jendrik24ORCID,Hecker-Nolting Stefanie8ORCID,Kabickova Edita25ORCID,Kager Leo2627ORCID,Kanerva Jukka28ORCID,Kester Lennart A.2ORCID,Kuijjer Marieke L.293031ORCID,Laurence Valérie32ORCID,Lervat Cyril33ORCID,Marchais Antonin18ORCID,Marec-Berard Perrine34ORCID,Mendes Cristina35ORCID,Merks Johannes H.M.236ORCID,Ory Benjamin37ORCID,Palmerini Emanuela38ORCID,Pantziarka Pan153940ORCID,Papakonstantinou Evgenia41ORCID,Piperno-Neumann Sophie33ORCID,Raciborska Anna42ORCID,Roundhill Elizabeth A.43ORCID,Rutkauskaite Vilma44ORCID,Safwat Akmal45ORCID,Scotlandi Katia46ORCID,Staals Eric L.47ORCID,Strauss Sandra J.48ORCID,Surdez Didier49ORCID,Sys Gwen M.L.50ORCID,Tabone Marie-Dominique51ORCID,Toulmonde Maud52ORCID,Valverde Claudia53ORCID,van de Sande Michiel A.J.54ORCID,Wörtler Klaus55ORCID,Campbell-Hewson Quentin56ORCID,McCabe Martin G.5758ORCID,Nathrath Michaela5960ORCID

Affiliation:

1. Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. 1

2. Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. 2

3. Pediatric Oncology, Regina Margherita Children’s Hospital, Turin, Italy. 3

4. Department of Public Health and Pediatrics, University of Turin, Turin, Italy. 4

5. Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria. 5

6. Pediatric Oncology Unit, Karolinska University Hospital, Stockholm, Sweden. 6

7. Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. 7

8. Center for Pediatric, Adolescent and Women’s Medicine, Klinikum Stuttgart—Olgahospital, Stuttgart Cancer Centre, Stuttgart, Germany. 8

9. Department of Musculoskeletal Radiology, Royal Orthopaedic Hospital NHS Foundation Trust, Birmingham, United Kingdom. 9

10. Department of Oncology, Oslo University Hospital, Oslo, Norway. 10

11. Paediatric Oncology, Royal Manchester Children’s Hospital, Central Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom. 11

12. Haematology/Oncology, Children’s Health Ireland at Crumlin, Dublin, Ireland. 12

13. Department of Pathology, UCL Cancer Institute, University College London, London, United Kingdom. 13

14. Pediatrics III, West German Cancer Center, University Hospital Essen, German Cancer Consortium (DKTK) Site Essen, Cancer Research Center (NCT) Cologne-Essen, University of Duisburg-Essen, Essen, Germany. 14

15. Patient and Parent Advocacy Group, FOSTER, Washington, District of Columbia. 15

16. Histopathology, The Royal National Orthopaedic Hospital NHS Trust, Stanmore, United Kingdom. 16

17. Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 17

18. Department of Oncology for Child and Adolescent, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. 18

19. U1015, Université Paris-Saclay, Villejuif, France. 19

20. Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. 20

21. Orthopaedic Oncology, The Royal National Orthopaedic Hospital NHS Trust, Stanmore, United Kingdom. 21

22. Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France. 22

23. EQ ONCOSARC, CRCT Inserm/UT3, ERL CNRS, Toulouse, France. 23

24. Tumour Orthopaedics, University Hospital Essen, German Cancer Consortium (DKTK) Site Essen, Cancer Research Center (NCT) Cologne-Essen, University of Duisburg-Essen, Essen, Germany. 24

25. Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic. 25

26. Pediatrics, St Anna Children’s Hospital, Medical University Vienna, Vienna, Austria. 26

27. St Anna Children’s Cancer Research Institute, Vienna, Austria. 27

28. Hematology-Oncology and Stem Cell Transplantation, HUS Helsinki University Hospital, New Children’s Hospital, Helsinki, Finland. 28

29. Computational Biology and Systems Medicine Group, Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway. 29

30. Pathology, Leiden University Medical Center, Leiden, the Netherlands. 30

31. Leiden Center for Computational Oncology, Leiden University Medical Center, Leiden, the Netherlands. 31

32. Department of Medical Oncology, Institut Curie, Paris, France. 32

33. Department of Pediatrics and AYA Oncology, Centre Oscar Lambret, Lille, France. 33

34. Institute of Hematology and Pediatric Oncology, Léon Bérard Center, Lyon, France. 34

35. Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal. 35

36. Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. 36

37. School of Medicine, Nantes Université, Nantes, France. 37

38. Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCCS Istituto Orthopedico Rizzoli, Bologna, Italy. 38

39. Anticancer Fund, Meise, Belgium. 39

40. The George Pantziarka TP53 Trust, London, United Kingdom. 40

41. Pediatric Hematology-Oncology, Ippokratio General Hospital of Thessaloniki, Thessaloniki, Greece. 41

42. Oncology and Surgical Oncology for Children and Youth, Institute of Mother and Child, Warsaw, Poland. 42

43. Children’s Cancer Research Group, Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom. 43

44. Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. 44

45. The Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. 45

46. Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 46

47. Orthopaedics and Trauma, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 47

48. Department of Oncology, University College London Hospitals NHS Foundation Trust, UCL Cancer Institute, London, United Kingdom. 48

49. Balgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), Zurich, Switzerland. 49

50. Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, Belgium. 50

51. Department of Hematology and Oncology, A. Trousseau Hospital, Sorbonne University, APHP, Paris, France. 51

52. Department of Medical Oncology, Institut Bergonié, Bordeaux, France. 52

53. Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain. 53

54. Orthopaedic Oncology, Leiden University Medical Centre, Leiden, the Netherlands. 54

55. Musculoskeletal Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 55

56. Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 56

57. Division of Cancer Sciences, School of Medical Sciences, The University of Manchester, Manchester, United Kingdom. 57

58. The Christie NHS Foundation Trust, Manchester, United Kingdom. 58

59. Children’s Cancer Research Center, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 59

60. Pediatric Oncology, Klinikum Kassel, Kassel, Germany. 60

Abstract

Abstract Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

Funder

Bone Cancer Research Trust

Foerderkreis Krebskranke Kinder eV Stuttgart

German Child Cancer Foundation

Publisher

American Association for Cancer Research (AACR)

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