title: Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: clinical daily practice reconsidered.
abstract: Cancer patients participating in studies involving experimental or diagnostic next-generation sequencing (NGS) procedures are confronted with the possibility of unsolicited findings. The Center for Personalized Cancer Treatment (CPCT), a Dutch consortium of cancer centers, is offering centralized large-scale NGS for the discovery of somatic tumor mutations with their germline DNA as reference. The CPCT aims to give all cancer patients with advanced disease stages access to tumor DNA analysis in order to improve selection for experimental therapy. In this article, our experiences at the CPCT will serve as an example to discuss the ethical and practical aspects regarding the management of unsolicited findings in personalized cancer research and treatment. Generic issues, relevant for all researchers in this field are discussed and illustrated by description of three patients faced with an unsolicited DNA finding, while they intended to be candidate for future anticancer treatment by participating in a trial that included NGS of both somatic and germline DNA. As options for DNA analysis expand and costs decrease rapidly, more and more patients are offered large-scale NGS testing. After reviewing current recommendations in literature, we conclude that classical informed consent procedures need to be adapted to become more explicit in asking patients if they want to be informed about unsolicited findings and if so, what level of detail of genetic risk information exactly they want to be returned after the analysis.
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands.
authors.forename: Rhodé M
authors.initials: RM
authors.lastname: Bijlsma
authors.affiliation: Julius Center for Health Science, Department Medical Humanities, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Annelien L
authors.initials: AL
authors.lastname: Bredenoord
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Christa G
authors.initials: CG
authors.lastname: Gadellaa-Hooijdonk
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Martijn Pj
authors.initials: MP
authors.lastname: Lolkema
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute (Antoni van Leeuwenhoek), Amsterdam, The Netherlands.
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Margreet Gem
authors.initials: MG
authors.lastname: Ausems
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute (Antoni van Leeuwenhoek), Amsterdam, The Netherlands.
authors.forename: Neeltje
authors.initials: N
authors.lastname: Steeghs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005817:Genetic Counseling / Q000941:ethics / Q000523:psychology / Q000592:standards*; D018095:Germ-Line Mutation; D006801:Humans; D007258:Informed Consent / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D017410:Practice Guidelines as Topic; D057285:Precision Medicine / Q000941:ethics / Q000523:psychology / Q000592:standards*