Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies

Author:

Bins Sander12,Cirkel Geert A.13,Gadellaa-Van Hooijdonk Christa G.13,Weeber Fleur14,Numan Isaac J.15,Bruggink Annette H.16,van Diest Paul J.17,Willems Stefan M.17,Veldhuis Wouter B.18,van den Heuvel Michel M.19,de Knegt Rob J.110,Koudijs Marco J.13,van Werkhoven Erik111,Mathijssen Ron H.J.12,Cuppen Edwin1512,Sleijfer Stefan1212,Schellens Jan H.M.11314,Voest Emile E.114,Langenberg Marlies H.G.13,de Jonge Maja J.A.12,Steeghs Neeltje113,Lolkema Martijn P.12

Affiliation:

1. Center for Personalized Cancer Treatment, Utrecht, The Netherlands

2. Departments of Medical Oncology, Rotterdam, The Netherlands

3. Department of Medical Oncology University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands

4. Departments of Molecular Oncology, Amsterdam, The Netherlands

5. Center for Molecular Medicine, Utrecht, The Netherlands

6. Central Biobank, Utrecht, The Netherlands

7. Departments of Pathology, Utrecht, The Netherlands

8. Radiology University Medical Center Utrecht, Utrecht, The Netherlands

9. Thoracic Oncology, Amsterdam, The Netherlands

10. Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands

11. Biometrics, Amsterdam, The Netherlands

12. Cancer Genomics Centre, Utrecht, The Netherlands

13. Medical Oncology and Clinical Pharmacology Antoni van Leeuwenhoek—The Netherlands Cancer Institute, Amsterdam, The Netherlands

14. Department of Pharmaceutical Sciences, Science Faculty Utrecht University, Utrecht, The Netherlands

Abstract

Abstract Background The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next-generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis. Patients and Methods Image-guided tumor biopsies were performed in advanced cancer patients. Samples were fresh frozen, vital tumor cellularity was estimated, and DNA was isolated after macrodissection of tumor-rich areas. Safety of the image-guided biopsy procedures was assessed by reporting of serious adverse events within 14 days after the biopsy procedure. Results Biopsy procedures were generally well tolerated. Major complications occurred in 2.1%, most frequently consisting of pain. In 7.3% of the percutaneous lung biopsies, pneumothorax requiring drainage occurred. The majority of samples (81%) contained a vital tumor percentage of at least 30%, from which at least 500 ng DNA could be isolated in 91%. Given our preset criteria, 74% of samples were of sufficient quality for biomarker discovery. The NGS results in this cohort were in line with those in other groups. Conclusion Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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