Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care

Abstract

Developments in genomics, including next-generation sequencing technologies, are expected to enable a more personalized approach to clinical care, with improved risk stratification and treatment selection. In oncology, personalized medicine is particularly advanced and increasingly used to identify oncogenic variants in tumor tissue that predict responsiveness to specific drugs. Yet, the translational research needed to validate these technologies will be conducted in patients with late-stage cancer and is expected to produce results of variable clinical significance and incidentally identify genetic risks. To explore the experiential context in which much of personalized cancer care will be developed and evaluated, we conducted a qualitative interview study alongside a pilot feasibility study of targeted DNA sequencing of metastatic tumor biopsies in adult patients with advanced solid malignancies. We recruited 29/73 patients and 14/17 physicians; transcripts from semi-structured interviews were analyzed for thematic patterns using an interpretive descriptive approach. Patient hopes of benefit from research participation were enhanced by the promise of novel and targeted treatment but challenged by non-findings or by limited access to relevant trials. Family obligations informed a willingness to receive genetic information, which was perceived as burdensome given disease stage or as inconsequential given faced challenges. Physicians were optimistic about long-term potential but conservative about immediate benefits and mindful of elevated patient expectations; consent and counseling processes were expected to mitigate challenges from incidental findings. These findings suggest the need for information and decision tools to support physicians in communicating realistic prospects of benefit, and for cautious approaches to the generation of incidental genetic information.

Patient hopes for diagnostic genomic sequencing: roles of uncertainty and social status

“…In line with the psychosocial and practical challenges of living with an unexplained or undiagnosed condition, participants' descriptions of their main hopes were largely aimed at receiving an explanation for the illness, information about treating it, a diagnosis (ie, a name or label for the condition), and information about disease risk in family members. These findings are similar to those found for oncology patients 5 and parents of pediatric patients with rare conditions 6 but are unlike findings for adults at risk for coronary artery disease whose hopes to help others or advance medical science figured more prominently. 4 Such similarities and differences from prior research suggest that how people prioritize hopes for genomic sequencing may vary by health context.…”

“…The current study extends prior research on people's hopes for genomic sequencing [4][5][6] by investigating predictors of hope in adult patients and parents of pediatric patients in a real-world, clinical setting. The hopes of patients and parents reflected personally relevant information that could potentially influence their psychological wellbeing, beliefs about the condition, and subsequent health decisions.…”

“…3 Prior studies reveal that at-risk adults, patients, and parents of pediatric patients hope to learn different kinds of information from diagnostic genomic sequencing results (eg, genetic cause, treatment). [4][5][6] One key question that has not been addressed is why patients hope for different kinds of information. Understanding factors that shape patient hope could inform the development of patient education and counseling approaches that foster hope in ways that acknowledge the strengths and limitations of genomic sequencing.…”

Patient preferences regarding incidental genomic findings discovered during tumor profiling

“…In response to growing concern over the handling of incidental germ-line variants discovered through next-generation sequencing of germ-line samples, the American College of Medical Genetics and Genomics (ACMG) published a set of guidelines in 2013 which initially recommended mandatory reporting, regardless of patient preference, for a well-defined set of variants in 57 genes, each with unequivocal disease association [9]. In response to the ensuing academic debate and call for revision from numerous genetic professionals and providers , the ACMG guidelines were re-issued the following year and an opt-out policy was recommended for patients who did not want to discover incidental findings [10][11][12][13][14].…”

“…Some in the oncology community suggest that reporting of incidental germ-line variants discovered as part of tumor profiling would substantially increase time expenditure, expense, and complexity of an already burdened clinical setting, and may negatively impact patients to the point where they may opt out from tumor testing altogether [14][15][16]. Others cite the debate as to whether there exists an obligation for laboratories to actively seek and report medically relevant germ-line mutations as outlined by the ACMG, particularly given that most patients undergoing tumor profiling have advanced disease and are themselves unlikely to benefit from the information on heritable diseases [1,9,13].…”