Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: clinical daily practice reconsidered

Bijlsma, Rhodé M; Bredenoord, Annelien L.; Gadellaa-Hooijdonk, Christa G; Lolkema, Martijn P.; Sleijfer, Stefan; Voest, Emile E.; Ausems, Margreet G. E. M.; Steeghs, Neeltje

doi:10.1038/ejhg.2016.27

Cited by 22 publications

(20 citation statements)

References 27 publications

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“…In the Netherlands, NGS is offered to adult cancer patients by the Center for Personalized Cancer Treatment, a Dutch consortium of cancer centers. Patients whose (somatic) NGS test results reveal unsolicited findings are informed by their oncologist and offered a referral to a clinical geneticist for further counseling and validation of the genetic variant in a diagnostic laboratory of a Clinical Genetics Center . Returning these unsolicited findings raises challenges for patients and their family members.…”

Section: Introductionmentioning

confidence: 99%

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients

et al. 2018

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The results of our study contribute to a better understanding of what cancer patients consider important and what may motivate and influence them when making decisions on the disclosure of unsolicited findings following NGS. We show how Joel Feinberg's classification of autonomy may help clinicians to better understand cancer patients' desire for autonomous decision making while also acknowledging the emotional and cognitive difficulties regarding the disclosure of unsolicited findings. These insights could be helpful for clinicians to guide patients through this complex process.

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Section: Introductionmentioning

confidence: 99%

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients

et al. 2018

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“…Innovative informed consent structures such as tiered and multidisciplinary approaches to educate patients will aid in this process [25]. In a recent cohort of cancer patients who underwent tumor sequencing with an NGS technology, 1% of reports revealed incidental findings [17]. This prevalence will vary according to the NGS methodology applied and cancer being studied; nevertheless, informed consent processes must include options for the patient to determine how to handle such scenarios.…”

Section: Discussionmentioning

confidence: 99%

Ethical Considerations of Neuro-oncology Trial Design in the Era of Precision Medicine

Gupta¹,

Smith²,

Broekman³

2019

Ethics of Innovation in Neurosurgery

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priority as part of a major US public health initiative. This new paradigm builds on the idea that cancers that harbor certain oncogenic mutations may be particularly susceptible to therapies that specifically target the aberrant proteins created by these mutations. As next-generation sequencing techniques have begun to uncover some of the mutations that drive the formation and growth of various cancers, applying this new therapeutic framework has the potential to revolutionize cancer management.The last decade has seen many innovations in the usage of targeted therapies. Vemurafenib, a targeted kinase inhibitor of the B-Raf protein variant produced by a V600E point mutation in BRAF, has been shown to reduce tumor burden and to improve overall survival in melanoma patients [1]. Similarly, gefitinib and erlotinib prolong survival for patients with non-small cell lung cancer by inhibiting overactive epidermal growth factor receptor caused by activating mutations in EGFR [2,3]. Precision medicine potentially has tremendous applicability in neuro-oncology and will allow patients to receive individualized therapies that target the genetic mutations underlying their diseases [4]. Indeed, early phase n-of-1 and small cohort investigational trials studies have already begun to demonstrate the potential of precision medicine in neuro-oncology [5][6][7].The successes and potential of precision medicine have also introduced new challenges not only related to clinical care, but also to ethics of clinical research. While there remains little doubt of the potential improvements in efficacy with precision medicine, characterizing and understanding these challenges can uphold the standards of patient autonomy, respect, and protection. In this discussion, we review pertinent ethical challenges to early phase clinical trials in precision medicine. AbstractThe field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges. We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

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“…Somatic multi-gene analysis with NGS can reveal germline deleterious variants as SFs [25,26]. The need for significant sequencing depth for these somatic analyses implies that the germline characteristic of a pathogenic variant (IARC class 5) will be suspected even before confirmation by constitutional analysis.…”

Section: Somatic Sequencing In Tumors or Other Human Tissuesmentioning

confidence: 99%

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations

et al. 2018

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In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients' representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the "actionability" of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

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Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: clinical daily practice reconsidered

Cited by 22 publications

References 27 publications

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients

Ethical Considerations of Neuro-oncology Trial Design in the Era of Precision Medicine

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations

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