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



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.



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.



Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank. The Oncologist 2017;22:33-40Implications for Practice: This study shows that it is safe to perform image-guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration. From the majority of the samples, sufficient DNA could be yielded to perform next-generation sequencing. These results indicate that the way is paved for consortia to prospectively collect fresh frozen tumor tissue.
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Medical Oncology.
Sander
S
Bins
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
Geert A
GA
Cirkel
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
Christa G
CG
Gadellaa-Van Hooijdonk
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Molecular Oncology.
Fleur
F
Weeber
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Center for Molecular Medicine.
Isaac J
IJ
Numan
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Central Biobank.
Annette H
AH
Bruggink
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Pathology.
Paul J
PJ
van Diest
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Pathology.
Stefan M
SM
Willems
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Wouter B
WB
Veldhuis
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Thoracic Oncology.
Michel M
MM
van den Heuvel
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Rob J
RJ
de Knegt
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
Marco J
MJ
Koudijs
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Biometrics.
Erik
E
van Werkhoven
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Medical Oncology.
Ron H J
RH
Mathijssen
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Center for Molecular Medicine.|Cancer Genomics Centre, Utrecht, The Netherlands.
Edwin
E
Cuppen
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Medical Oncology.|Cancer Genomics Centre, Utrecht, The Netherlands.
Stefan
S
Sleijfer
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Medical Oncology and Clinical Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
Jan H M
JH
Schellens
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
Emile E
EE
Voest
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
Marlies H G
MH
Langenberg
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Departments of Medical Oncology.
Maja J A
MJ
de Jonge
Center for Personalized Cancer Treatment, Utrecht, The Netherlands.|Medical Oncology and Clinical Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Neeltje
N
Steeghs
Center for Personalized Cancer Treatment, Utrecht, The Netherlands m.lolkema@erasmusmc.nl.|Departments of Medical Oncology.
Martijn P
MP
Lolkema
D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D061705:Image-Guided Biopsy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009426:Netherlands
D014408:Biomarkers, Tumor
Advanced cancer patients; Feasibility and safety; Image‐guided biopsy procedures; Next‐generation sequencing; Personalized cancer treatment; Precision oncology
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