Stacy W. Gray

Cancer Information Scanning and Seeking in the General Population

The amount of cancer-related information available in the media and other sources continues to increase each year. We wondered how people make use of such content in making specific health decisions. We studied both the information they actively seek (“seeking”) and that which they encounter in a less purposive way (“scanning”) through a nationally representative survey of adults aged 40–70 years (n = 2,489) focused on information use around three prevention behaviors (dieting, fruit and vegetable consumption, and exercising) and three screening test behaviors (prostate-specific antigen, colonoscopy, mammogram). Overall, respondents reported a great deal of scanning and somewhat less seeking (on average 62% versus 28% for each behavior), and they used a range of sources including mass media, interpersonal conversations, and the Internet, alongside physicians. Seeking was predicted by female gender, age of 55–64 vs. 40–44, higher education, Black race and Hispanic ethnicity, and being married. Scanning was predicted by older age, female gender, and education. Respondents were fairly consistent in their place on a typology of scanning and seeking across behaviors. Seeking was associated with all six behaviors, and scanning was associated with three of six behaviors.

Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK-Rearranged Lung Adenocarcinomas

Introduction: ALK gene rearrangements occur in approximately 5% of lung adenocarcinomas (ACAs), leading to anaplastic lymphoma kinase (ALK) overexpression and predicting response to targeted therapy. Fluorescence in situ hybridization (FISH) is the standard procedure for detection of ALK rearrangements in lung ACA but requires specialized equipment and expertise. Immunohistochemistry (IHC) for ALK protein overexpression is a promising screening modality, with reports of newer antibodies showing excellent sensitivity and specificity for ALK-rearranged lung ACA. Methods: In this study, we analyzed ALK IHC (5A4 clone) in 186 cases from our clinical service and compared it with ALK FISH and EGFR and KRAS mutation status. Results: Twelve cases had concordant ALK protein overexpression and ALK rearrangement by FISH. Three ALK-rearranged cases lacked ALK protein expression. Of these discrepant cases, one had a coexisting EGFR mutation and a subtle atypical ALK rearrangement manifested as a break in the 5′ centromeric portion of the FISH probe. One case had a concurrent BRAF mutation. Follow-up testing on a metastasis revealed absence of the ALK rearrangement, with persistent BRAF mutation. In one ALK-rearranged protein negative case, very limited tissue remained for ALK IHC, raising the possibility of false negativity because of protein expression heterogeneity. Importantly, ALK protein expression was detected in one case initially thought not to have an ALK rearrangement. In this case, FISH was falsely negative because of interference by benign reactive nuclei. After correcting for these cases, ALK IHC was 93% sensitive and 100% specific as compared with FISH. Conclusions: ALK IHC improves the detection of ALK rearrangements when used together with FISH, and its use in lung ACA genetic testing algorithms should be considered.

Physicians’ Attitudes About Multiplex Tumor Genomic Testing

PURPOSE Although predictive multiplex somatic genomic tests hold the potential to transform care by identifying targetable alterations in multiple cancer genes, little is known about how physicians will use such tests in practice. PARTICIPANTS AND METHODS Before the initiation of enterprise-wide multiplex testing at a major cancer center, we surveyed all clinically active adult cancer physicians to assess their current use of somatic testing, their attitudes about multiplex testing, and their genomic confidence. RESULTS A total of 160 physicians participated (response rate, 61%): 57% were medical oncologists; 29%, surgeons; 14% radiation oncologists; 37%, women; and 83%, research principal investigators. Twenty-two percent of physicians reported low confidence in their genomic knowledge. Eighteen percent of physicians anticipated testing patients infrequently (≤ 10%), whereas 25% anticipate testing most patients (≥ 90%). Higher genomic confidence was associated with wanting to test a majority of patients (adjusted odds ratio [OR], 6.09; 95% CI, 2.1 to 17.5) and anticipating using actionable (adjusted OR, 2.46; 95% CI, 1.2 to 5.2) or potentially actionable (adjusted OR, 2.89; 95% CI, 1.1 to 7.9) test results to inform treatment recommendations. Forty-two percent of physicians endorsed disclosure of uncertain genomic findings to patients. CONCLUSION Physicians at a tertiary-care National Cancer Institute-designated comprehensive cancer center varied considerably in how they planned to incorporate predictive multiplex somatic genomic tests into practice and in their attitudes about the disclosure of genomic information of uncertain significance. Given that many physicians reported low genomic confidence, evidence-based guidelines and enhanced physician genomic education efforts may be needed to ensure that genomically guided cancer care is adequately delivered.

Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non–Small Cell Lung Cancer

CONTEXT A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older. OBJECTIVE To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare. MAIN OUTCOME MEASURE Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009. RESULTS The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings. CONCLUSION Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.

Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium

As genomic and exomic testing expands in both the research and clinical arenas, determining whether, how, and which incidental findings to return to the ordering clinician and patient becomes increasingly important. Although opinion is varied on what should be returned to consenting patients or research participants, most experts agree that return of medically actionable results should be considered. There is insufficient evidence to fully inform evidence-based clinical practice guidelines regarding return of results from genome-scale sequencing, and thus generation of such evidence is imperative, given the rapidity with which genome-scale diagnostic tests are being incorporated into clinical care. We present an overview of the approaches to incidental findings by members of the Clinical Sequencing Exploratory Research network, funded by the National Human Genome Research Institute, to generate discussion of these approaches by the clinical genomics community. We also report specific lists of “medically actionable” genes that have been generated by a subset of investigators in order to explore what types of findings have been included or excluded in various contexts. A discussion of the general principles regarding reporting of novel variants, challenging cases (genes for which consensus was difficult to achieve across Clinical Sequencing Exploratory Research network sites), solicitation of preferences from participants regarding return of incidental findings, and the timing and context of return of incidental findings are provided.Genet Med 2013; 15: 860–867Genetics in Medicine (2013); doi:10.1038/gim.2013.133

A survey of informatics approaches to whole-exome and whole-genome clinical reporting in the electronic health record

Purpose:Genome-scale clinical sequencing is being adopted more broadly in medical practice. The National Institutes of Health developed the Clinical Sequencing Exploratory Research (CSER) program to guide implementation and dissemination of best practices for the integration of sequencing into clinical care. This study describes and compares the state of the art of incorporating whole-exome and whole-genome sequencing results into the electronic health record, including approaches to decision support across the six current CSER sites.Methods:The CSER Medical Record Working Group collaboratively developed and completed an in-depth survey to assess the communication of genome-scale data into the electronic health record. We summarized commonalities and divergent approaches.Results:Despite common sequencing platform (Illumina) adoptions, there is a great diversity of approaches to annotation tools and workflow, as well as to report generation. At all sites, reports are human-readable structured documents available as passive decision support in the electronic health record. Active decision support is in early implementation at two sites.Conclusion:The parallel efforts across CSER sites in the creation of systems for report generation and integration of reports into the electronic health record, as well as the lack of standardized approaches to interfacing with variant databases to create active clinical decision support, create opportunities for cross-site and vendor collaborations.Genet Med 15 10, 824–832.Genetics in Medicine (2013); 15 10, 824–832. doi:10.1038/gim.2013.120

How do cancer patients navigate the public information environment? Understanding patterns and motivations for movement among information sources.

Little is known about how patients move among information sources to fulfill unmet needs. We interviewed 43 breast, prostate, and colorectal cancer patients. Using a grounded theory approach, we identified patterns and motivations for movement among information sources. Overall, patients reported using one source (e.g., newspaper) followed by the use of another source (e.g., Internet), and five key motivations for such cross-source movement emerged. Patients’ social networks often played a central role in this movement. Understanding how patients navigate an increasingly complex information environment may help clinicians and educators to guide patients to appropriate, high-quality sources.

Oncologists' and Cancer Patients' Views on Whole-Exome Sequencing and Incidental Findings: Results from The CanSeq Study

Purpose:Although targeted sequencing improves outcomes for many cancer patients, it remains uncertain how somatic and germ-line whole-exome sequencing (WES) will integrate into care.Methods:We conducted surveys and interviews within a study of WES integration at an academic center to determine oncologists’ attitudes about WES and to identify lung and colorectal cancer patients’ preferences for learning WES findings.Results:One-hundred sixty-seven patients (85% white, 58% female, mean age 60) and 27 oncologists (22% female) participated. Although oncologists had extensive experience ordering somatic tests (median 100/year), they had little experience ordering germ-line tests. Oncologists intended to disclose most WES results to patients but anticipated numerous challenges in using WES. Patients had moderately low levels of genetic knowledge (mean 4 correct out of 7). Most patients chose to learn results that could help select a clinical trial, pharmacogenetic and positive prognostic results, and results suggesting inherited predisposition to cancer and treatable noncancer conditions (all ≥95%). Fewer chose to receive negative prognostic results (84%) and results suggesting predisposition to untreatable noncancer conditions (85%).Conclusion:The majority of patients want most cancer-related and incidental WES results. Patients’ low levels of genetic knowledge and oncologists’ inexperience with large-scale sequencing present challenges to implementing paired WES in practice.Genet Med 18 10, 1011–1019.

Anti–PD-1 Inhibitor–Related Pneumonitis in Non–Small Cell Lung Cancer

Use of immune checkpoint inhibitors is increasing. Some patients with NSCLC treated with nivolumab develop a radiographic cryptogenic organizing pneumonia (COP) pattern of PD-1 inhibitor–related pneumonitis. Recognition of the radiographic pattern is needed for prompt diagnosis and management. The recent approval of two PD-1 inhibitors for the treatment of non–small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti–PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a “pneumonitis flare,” in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor–related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event. Cancer Immunol Res; 4(4); 289–93. ©2016 AACR.

Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing

BACKGROUND Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP). OBJECTIVE To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP. DESIGN Longitudinal, prospective cohort study. SETTING Online survey before and 6 months after results. PARTICIPANTS DTC PGT consumers. MEASUREMENTS Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCPs understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses. RESULTS Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%). LIMITATION Participants may not be representative of all DTC PGT consumers. CONCLUSION A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve. PRIMARY FUNDING SOURCE National Institutes of Health.