Preparing for the unexpected: Recommendations for returning secondary findings in late-stage cancer care.

PURPOSE: We conducted qualitative interviews with patients with cancer and providers to identify gaps in clinical care and highlight care delivery solutions for the return of secondary germline findings. METHODS: Twelve patients and 19 cancer providers from the United States were interviewed between January 2019 and May 2021. Interviews elicited feedback about patient information needs, emotional responses to secondary findings, and recommendations for improving pre-test education. RESULTS: Patients' responses ranged from gratitude to regret, depending on how much pre-test counseling they received before tumor testing. Providers cited insufficient clinic time as a major barrier to pretest education, favoring online support tools and standardized pre-test education models. Providers had differing perspectives on how pre-test education should be integrated into clinical workflows but agreed that it should include the differences between somatic and germline testing, the likelihood of medically actionable findings, and the possibility of being referred to a genetics provider. CONCLUSION: The spectrum of participants' responses to their secondary findings underscores the importance of adequate pre-test discussions before somatic sequencing. Although educational interventions could address patients' information needs and augment traditional pre-test counseling, health care systems, labs, and genetic providers may be called on to play greater roles in pre-test education.

Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

The Association between Polluted Neighborhoods and TP53-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Poor patients often reside in neighborhoods of lower socioeconomic status (SES) with high levels of airborne pollutants. They also have higher mortality from non-small cell lung cancer (NSCLC) than those living in wealthier communities. We investigated whether living in polluted neighborhoods is associated with somatic mutations linked with lower survival rates, i.e., TP53 mutations. METHODS: In a retrospective cohort of 478 patients with NSCLC treated at a comprehensive cancer center between 2015 and 2018, we used logistic regression to assess associations between individual demographic and clinical characteristics, including somatic TP53 mutation status and environmental risk factors of annual average particulate matter (PM2.5) levels, and neighborhood SES. RESULTS: 277 patients (58%) had somatic TP53 mutations. Of those, 45% lived in neighborhoods with "moderate" Environmental Protection Agency-defined PM2.5 exposure, compared with 39% of patients without TP53 mutations. We found significant associations between living in neighborhoods with "moderate" versus "good" PM2.5 concentrations and minority population percentage [OR, 1.06; 95% confidence interval (CI), 1.04-1.08]. There was a significant association between presence of TP53 mutations and PM2.5 exposure (moderate versus good: OR, 1.66; 95% CI, 1.02-2.72) after adjusting for patient characteristics, other environmental factors, and neighborhood-level SES. CONCLUSIONS: When controlling for individual- and neighborhood-level confounders, we find that the odds of having a TP53-mutated NSCLC are increased in areas with higher PM2.5 exposure. IMPACT: The link between pollution and aggressive biology may contribute to the increased burden of adverse NSCLC outcomes in individuals living in lower SES neighborhoods.