Abstract ED02-04: Returning germline results to cancer patients
Authors: Plon Sharon E. 
Published: May 2016

Abstract
Patient-centered communication, defined as providing clear, understandable information with active patient participation, can be especially challenging in the return of germline sequencing results for cancer patients. In this session, Dr. Plon will review some of the recently developed projects that involve performing whole exome or genome sequencing of pediatric and adult cancer patients including the return of germline results to patients/families as part of the study design. Several trials are well underway through the NHGRI Clinical Sequencing Exploratory Research Consortium including the Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care (BASIC3) study which examines the clinical utility of tumor and germline WES in the setting of solid tumor (both CNS and non-CNS pediatric oncology patients). Issues that investigators need to consider which will be discussed include: (1) consenting patients/parents to clinical genomics, (2) the range of pathogenic mutations related to the patient's phenotype being returned, (3) how to handle variants of uncertain significance in cancer genes, (4) how to approach the return of incidental findings, (5) planning for the possibility of patient demise prior to return of results and (5) what forms of validation are being used prior to returning results including the issue of the potential for inferring germline results in tests that are designed to be “tumor only”.
Dr. Plon will provide their experience with disclosure of germline whole exome sequencing results to parents of recently diagnosed childhood cancer patients in the BASIC3 study. The WES are disclosed to families by the patient's pediatric oncologist and one of two study genetic counselors. The disclosure visits (over 150 to date) are audio-recorded, transcribed and the text analyzed by Dr. Richard Street and his team using previously validated methodologies. The transcripts are analyzed for both the number of statements made by practitioners and families as well as more detailed analysis of disclosures with clinically important findings. The primary findings were: (a) the oncologists from this single large childhood cancer center varied greatly in how they utilized the genetic counselors during the encounters for discussion of both tumor and germline findings (b) genetic counselors made more recommendations based on the WES findings than did oncologists; (c) clinicians engaged in more partnership-building and supportive talk after they gained more experience presenting WES reports; and (e) checking for parent understanding was infrequent. Through this analysis we have developed a more streamlined format for disclosure which is generalizable to other germline findings and will be discussed in the session including: (1) there is substantial interest from families in obtaining germline findings when embarking on tumor sequencing, (2) families are less concerned about separating tumor and germline findings - their primary emphasis is on those genomic findings that result in specific actions for the patient or family members and (3) discussion of the more technical but less clinically relevant findings such as variants of uncertain significance can be minimized in disclosing genomic results. Supported by NHGRI/NCI 1U01HG006485.
Citation Format: Sharon E. Plon. Returning germline results to cancer patients. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr ED02-04.