Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
J Transl Med ; 18(1): 431, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183308

RESUMO

BACKGROUND: Clinical whole exome sequencing was introduced in an Australian centre in 2017, as an alternative to Sanger sequencing. We aimed to identify predictors of cancer physicians' somatic mutation test ordering behaviour. METHODS: A validated instrument assessed somatic mutation test ordering, genomic confidence, perceived utility of tumour molecular profiling, and percent of patients eligible for targeted therapy. A cash incentive was included in 189/244 questionnaires which were mailed to all Queensland cancer specialists in November 2018. RESULTS: 110 participated (response rate 45%); 54.7% oncologists, and the remainder were surgeons, haematologists and pulmonologists. Oncologists were more likely to respond (p = 0.008), and cash incentive improved the response rate (p < 0.001). 67/102 (65.7%) of physicians ordered ≥ 5 somatic mutation tests annually. Oncologists saw 86.75 unique patients monthly and ordered 2.33 somatic mutation tests (2.2%). An average of 51/110 (46.1%) reported having little/no genomic confidence. Logistic regression identified two significant predictors of somatic mutation test ordering: being an oncologist (OR 3.557, CI 1.338-9.456; p = 0.011) and having greater confidence in interpreting somatic results (OR 5.926, CI 2.230-15.74; p < 0.0001). CONCLUSIONS: Consistent with previous studies, the majority of cancer physicians ordered somatic mutation tests. However, the percentage of patients on whom tests were ordered was low. Almost half respondents reported low genomic confidence. Somatic mutation test ordering was higher amongst oncologists and those with increased confidence in interpreting somatic variants. It is unclear whether genomically confident individuals ordered more tests or whether ordering more tests increased genomic confidence. Educational interventions could improve confidence and enhance test ordering behaviour.

2.
Lancet Oncol ; 21(10): e488-e494, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002444

RESUMO

Patient-reported outcome (PRO) measures describe how a patient feels or functions and are increasingly being used in benefit-risk assessments in the development of cancer drugs. However, PRO research objectives are often ill-defined in clinical cancer trials, which can lead to misleading conclusions about patient experiences. The estimand framework is a structured approach to aligning a clinical trial objective with the study design, including endpoints and analysis. The estimand framework uses a multidisciplinary approach and can improve design, analysis, and interpretation of PRO results. On the basis of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use E9(R1) addendum, we provide an overview of the estimand framework intended for a multistakeholder audience. We apply the estimand framework to a hypothetical trial for breast cancer, using physical function to develop specific PRO research objectives. This Policy Review is not an endorsement of a specific study design or outcome; rather, it is meant to show the application of principles of the estimand framework to research study design and add to ongoing discussion. Use of the estimand framework to review medical products and label PROs in oncology can improve communication between stakeholders and ultimately provide a clearer interpretation of patient experience in the development of oncological drugs.


Assuntos
Protocolos de Ensaio Clínico como Assunto , Oncologia/normas , Medidas de Resultados Relatados pelo Paciente , Antineoplásicos/uso terapêutico , Interpretação Estatística de Dados , Desenvolvimento de Medicamentos/legislação & jurisprudência , Desenvolvimento de Medicamentos/normas , Humanos , Comunicação Interdisciplinar , Oncologia/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Projetos de Pesquisa/normas
3.
Artigo em Inglês | MEDLINE | ID: mdl-32923869

RESUMO

PURPOSE: The evolution of precision oncology increasingly requires oncologists to incorporate genomic testing into practice. Yet, providers' confidence with genomic testing is poorly documented. This article describes medical oncologists' confidence with genomic testing and the association between genomic confidence and test use. METHODS: We used data from the 2017 National Survey of Precision Medicine in Cancer Treatment to characterize oncologists' confidence with genomic testing. Genomic confidence was examined separately by type of test user: next-generation sequencing (NGS) only, gene expression (GE) only, both NGS and GE, or nonuser. Predictors of genomic confidence were examined with multinomial logistic regression. The association between genomic confidence and test use was examined with multivariable linear regression. RESULTS: More than 75% of genomic test users were either moderately or very confident about using results from multimarker tumor panel tests to guide patient care. Confidence with using multimarker tumor panel tests was highest among both NGS and GE test users, with 60.1% very confident in using test results, and lowest among NGS-only test users, with 38.2% very confident in using test results. Oncologists were most confident in using single-gene tests and least confident in using whole-genome or -exome sequencing to guide patient care. Genomic confidence was positively associated with self-reported test use. In adjusted models, training in genomics, larger patient volume, and treating patients with solid tumors predicted higher genomic confidence. Onsite pathology services and receipt of electronic medical record alerts for genomic testing predicted lower genomic confidence. CONCLUSION: Oncologists' confidence varies by testing platform, patient volume, genomic training, and practice infrastructure. Research is needed to identify modifiable factors that can be targeted to enhance provider confidence with genomic testing.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32923887

RESUMO

PURPOSE: Evidence-based somatic and germline sequencing has transformed cancer care and improves patient outcomes. However, patients' low genetic literacy and misunderstanding of their own genomic results poses a threat to the realization of precision oncology. To optimize patient genomic comprehension, we developed a Web-based, patient-directed, genomic sequencing education and return-of-results tool, HOPE-Genomics. METHODS: The HOPE-Genomics prototype included somatic and germline sequencing results, embedded multimedia genomic education, and interactive features (eg, request for genetic counseling). Between January and April 2018, we elicited feedback on tool usability and comprehensiveness through participant surveys, 4 focus groups of patients with cancer and their family members, and 3 provider focus groups (comprising 8 patients, 5 family members, and 19 providers). RESULTS: We identified themes in patient/family tool-related responses, including the desire to view a patient-friendly report, a desire to receive multiple types of genomic information (eg, prognostic and uncertain), high acceptability of report content, and interest in tool-enabled access to genetic counseling. Major themes from the clinician focus groups included believing the tool could help patients formulate questions and facilitate patients' communication of results to family members. However, there were diverse responses from all participants in terms of tool implementation (ie, timing and nature of report release). Some participants preferred report release before meeting with the provider, and others preferred it during the appointment. Additionally, some clinicians were concerned about providing prognostic and treatment information through the tool. CONCLUSION: There was high acceptability and interest from patients, family members, and providers in a patient-directed genomics report. Future work will determine whether direct-to-patient reporting of genomic results improves patient knowledge, care engagement, and compliance with genomically guided interventions.

5.
J Natl Compr Canc Netw ; 18(7): 866-872, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32634780

RESUMO

BACKGROUND: Clinical adoption of the sequencing of circulating tumor DNA (ctDNA) for cancer has rapidly increased in recent years. This sequencing is used to select targeted therapy and monitor nonresponding or progressive tumors to identify mechanisms of therapeutic resistance. Our study objective was to review available coverage policies for cancer ctDNA-based testing panels to examine trends from 2015 to 2019. METHODS: We analyzed publicly available private payer policies and Medicare national coverage determinations and local coverage determinations (LCDs) for ctDNA-based panel tests for cancer. We coded variables for each year representing policy existence, covered clinical scenario, and specific ctDNA test covered. Descriptive analyses were performed. RESULTS: We found that 38% of private payer coverage policies provided coverage of ctDNA-based panel testing as of July 2019. Most private payer policy coverage was highly specific: 87% for non-small cell lung cancer, 47% for EGFR gene testing, and 79% for specific brand-name tests. There were 8 final, 2 draft, and 2 future effective final LCDs (February 3 and March 15, 2020) that covered non-FDA-approved ctDNA-based tests. The draft and future effective LCDs were the first policies to cover pan-cancer use. CONCLUSIONS: Coverage of ctDNA-based panel testing for cancer indications increased from 2015 to 2019. The trend in private payer and Medicare coverage is an increasing number of coverage policies, number of positive policies, and scope of coverage. We found that Medicare coverage policies are evolving to pan-cancer uses, signifying a significant shift in coverage frameworks. Given that genomic medicine is rapidly changing, payers and policymakers (eg, guideline developers) will need to continue to evolve policies to keep pace with emerging science and standards in clinical care.

6.
Support Care Cancer ; 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32537684

RESUMO

PURPOSE: The Institute of Medicine recommends that cancer patients receive survivorship care plans (SCP) summarizing information important to the individual's long-term care. The various components of SCPs have varying levels of evidence supporting their impact. We surveyed medical oncologists to better understand how they perceived the relative value of different SCP components. METHODS: Medical oncologists caring for patients in diverse US practice settings were surveyed (357 respondents; participation rate 52.9%) about their perceptions of the usefulness of various components of SCPs to both patients and primary care physicians (PCPs). RESULTS: Oncologists perceived treatment summaries as "very useful" for PCPs but were less likely to perceive them as "very useful" for patients (55% vs. 40%, p < 0.001). Information about the psychological effects of cancer (41% vs. 29%; p < 0.001) and healthy behaviors (67% vs. 41%; p < 0.001) were considered more useful to patients than to PCPs. From 3 to 20% of oncologists believed that any given component of the SCP was not useful to either PCPs or patients. Oncologists who perceived SCPs to be more useful tended to be female or to practice in settings with a fully implemented electronic health record. CONCLUSIONS: Oncologists do not perceive all components of SCPs to be equally useful to both patients and PCPs. To be successfully implemented, the SCP should be efficiently tailored to the unique needs and knowledge of patients and their PCPs. A minority of oncologists appear to be late adopters, suggesting that some resistance to the adoption of SCPs remains.

7.
JAMA Netw Open ; 3(1): e1918586, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899533

RESUMO

Importance: Understanding adoption of new cancer therapies may help identify opportunities to increase use for high-value indications. Objective: To determine whether use of bevacizumab in 2005 to 2006 by oncologists' peers was associated with greater bevacizumab use among oncologists in 2007 to 2010. Design, Setting, and Participants: This cohort study of physicians and their patients took place in 51 randomly selected hospital referral regions in the United States. Participants were 44 012 fee-for-service Medicare beneficiaries aged 65 years or older with cancers of the colorectum, lung, breast, kidney, brain, or ovary treated by 3261 oncologists in 2005 to 2010 and assigned to one of 252 communities. Data were analyzed in 2017 to 2018. Exposures: Among patients treated with chemotherapy during 2007 to 2010 by an oncologist who had not treated patients with bevacizumab in 2005 to 2006, models assessed the association of bevacizumab use with rates of bevacizumab use in their physician's community of connected physicians in 2005 to 2006. Models adjusted for patient and physician characteristics and physician, practice, and community random effects. Main Outcomes and Measures: Receipt of bevacizumab. Results: A total of 34 750 patients (14 126 [40.6%] aged ≥75 years; 21 321 [61.4%] female) with cancers of the colorectum, lung, breast, kidney, brain, and ovary were treated with chemotherapy in 2005 to 2006 in the 51 hospital referral regions. Among 9262 patients treated in 2007 to 2010 by 829 physicians whose patients did not use bevacizumab in 2005 to 2006, 3654 (39.5%) were aged 75 years or older and 6227 (67.2%) were female. The rate of bevacizumab use relative to other chemotherapy in 2007 to 2010 by tertile of use (bevacizumab for <4.4%, 4.4%-6.2%, and >6.2% of all patients receiving chemotherapy) among their physician's peers in 2005 to 2006 was 10.0%, 9.5%, and 13.6%, respectively. After adjustment, use of bevacizumab in 2007 to 2010 was greater among physicians in communities with the highest rates of bevacizumab use in 2005 to 2006 compared with those whose peers were in the lowest tertile of bevacizumab use in 2005 to 2006 (adjusted odds ratio, 1.64; 95% CI, 1.20-2.25). Conclusions and Relevance: This study found that an increase in oncologists' adoption and use of bevacizumab in the years after its approval was associated with their peer physicians being earlier adopters. As organizations seek to provide better care at lower costs, interventions that leverage physician ties may help to promote adoption of high-value use of new cancer treatments and deimplementation of low-value therapies.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Oncologistas/estatística & dados numéricos , Infuência dos Pares , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Planos de Pagamento por Serviço Prestado , Feminino , Humanos , Masculino , Medicare , Neoplasias/tratamento farmacológico , Razão de Chances , Encaminhamento e Consulta , Estados Unidos
8.
Pharmacol Ther ; 207: 107458, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31863816

RESUMO

Circulating tumor DNA holds substantial promise as an early detection biomarker, particularly for cancers that do not have currently accepted screening methodologies, such as ovarian, pancreatic, and gastric cancers. Many features intrinsic to ctDNA analysis may be leveraged to enhance its use as an early cancer detection biomarker: including ctDNA fragment lengths, DNA copy number variations, and associated patient phenotypic information. Furthermore, ctDNA testing may be synergistically used with other multi-omic biomarkers to enhance early detection. For instance, assays may incorporate early detection proteins (i.e., CA-125), epigenetic markers, circulating tumor RNA, nucleosomes, exosomes, and associated immune markers. Many companies are currently competing to develop a marketable early cancer detection test that leverages ctDNA. Although some hurdles (like early stage disease assay accuracy, high implementation costs, confounding from clonal hematopoiesis, and lack of clinical utility studies) need to be addressed before integration into healthcare, ctDNA assays hold substantial potential as an early cancer screening test.

9.
Genet Med ; 21(12): 2781-2790, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189963

RESUMO

PURPOSE: As exome and genome sequencing (ES/GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) Consortium collaboration, we evaluated participants' psychological outcomes across multiple clinical settings. METHODS: We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale [HADS]/Generalized Anxiety Disorder 7-item), depressive symptoms (HADS/Personal Health Questionnaire 9-item), and multidimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/Feelings About Genomic Testing Results scale). RESULTS: Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to postdisclosure revealed an overall trend for a decrease in participants' anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses. CONCLUSION: Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.


Assuntos
Revelação/ética , Estresse Psicológico/psicologia , Sequenciamento Completo do Exoma/ética , Adulto , Ansiedade/psicologia , Mapeamento Cromossômico , Depressão/psicologia , Emoções , Exoma , Feminino , Testes Genéticos/ética , Testes Genéticos/métodos , Genômica/métodos , Humanos , Masculino , Incerteza
10.
Med Care ; 57(6): 468-474, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31008900

RESUMO

BACKGROUND: The intensity of end-of-life care varies substantially both within and between areas. Differing practice patterns of individual physicians are likely influenced by their peers. OBJECTIVE: To assess whether intensity of end-of-life care previously provided by a physician's peers influences patterns of care at the end-of-life for that physician's patients. RESEARCH DESIGN: Observational study. SUBJECTS: A total of 185,947 fee-for-service Medicare enrollees with cancer who died during 2006-2010 who were treated by 26,383 physicians. MEASURES: Spending in the last month of life, >1 emergency room visit, >1 hospitalization, intensive care unit admission in the last month of life, chemotherapy within 2 weeks of death, no/late hospice, terminal hospitalization. RESULTS: Mean (SD) spending in the last month of life was $16,237 ($17,124). For each additional $1000 of spending for a peer physician's patients in the prior year, spending for the ego physician's patients was $83 higher (P<0.001). Among physicians with peers both in and out of their practice, more of the peer effect was explained by physicians outside of the practice ($72 increase for each $1000 increase by peer physicians' patients, P<0.001) than peer physicians in the practice ($27 for each $1000 increase by within-practice peer physicians' patients, P=0.01). Results were similar across the other measures of end-of-life care intensity. CONCLUSIONS: Physician's peers exert influence on the intensity of care delivered to that physician's patients at the end-of-life. Physician education efforts led by influential providers and provider organizations may have potential to improve the delivery of high-value end-of-life care.


Assuntos
Medicare/economia , Neoplasias/terapia , Grupo Associado , Padrões de Prática Médica/estatística & dados numéricos , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Neoplasias/mortalidade , Estados Unidos
11.
J Clin Oncol ; : JCO1800328, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30339520

RESUMO

PURPOSE: To determine the potential for detection of incidental germline cancer predisposition mutations through cell-free DNA (cfDNA) analyses in patients who underwent solid tumor somatic mutation evaluation. PATIENTS AND METHODS: Data were evaluated from 10,888 unselected patients with advanced (stage III/IV) cancer who underwent Guardant360 testing between November 2015 and December 2016. The main outcome was prevalence of putative germline mutations identified among 16 actionable hereditary cancer predisposition genes. RESULTS: More than 50 cancer types were studied, including lung (41%), breast (19%), colorectal (8%), prostate (6%), pancreatic (3%), and ovarian (2%). Average patient age was 63.5 years (range, 18 to 95 years); 43% were male. One hundred and fifty-six individuals (1.4%) had suspected hereditary cancer mutations in 11 genes. Putative germline mutations were more frequent in individuals younger than 50 years versus those 50 years and older (3.0% v 1.2%, respectively; P < .001). Highest yields of putative germline findings were in patients with ovarian (8.13%), prostate (3.46%), pancreatic (3.34%), and breast (2.2%) cancer. Putative germline mutation identification was consistent among 12 individuals with multiple samples. Patients with circulating tumor DNA copy number variation and/or reversion mutations suggestive of functional loss of the wild-type allele in the tumor DNA also are described. CONCLUSION: Detection of putative germline mutations from cfDNA is feasible across multiple genes and cancer types without prior mutation knowledge. Many mutations were found in cancers without clear guidelines for hereditary cancer genetic counseling/testing. Given the clinical significance of identifying hereditary cancer predisposition for patients and their families as well as targetable germline alterations such as in BRCA1 or BRCA2, research on the best way to validate and return potential germline results from cfDNA analysis to clinicians and patients is needed.

12.
Cancer Med ; 7(11): 5832-5842, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30264921

RESUMO

Historically, non-small-cell lung cancer (NSCLC) patients who are non-white, have low incomes, low educational attainment, and non-private insurance have worse survival. We assessed whether differences in survival were attributable to sociodemographic factors, clinical characteristics at diagnosis, or treatments received. We surveyed a multiregional cohort of patients diagnosed with NSCLC from 2003 to 2005 and followed through 2012. We used Cox proportional hazard analyses to estimate the risk of death associated with race/ethnicity, annual income, educational attainment, and insurance status, unadjusted and sequentially adjusting for sociodemographic factors, clinical characteristics, and receipt of surgery, chemotherapy, and radiotherapy. Of 3250 patients, 64% were white, 16% black, 7% Hispanic, and 7% Asian; 36% of patients had incomes <$20 000/y; 23% had not completed high school; and 74% had non-private insurance. In unadjusted analyses, black race, Hispanic ethnicity, income <$60 000/y, not attending college, and not having private insurance were all associated with an increased risk of mortality. Black-white differences were not statistically significant after adjustment for sociodemographic factors, although patients with patients without a high school diploma and patients with incomes <$40 000/y continued to have an increased risk of mortality. Differences by educational attainment were not statistically significant after adjustment for clinical characteristics. Differences by income were not statistically significant after adjustment for clinical characteristics and treatments. Clinical characteristics and treatments received primarily contributed to mortality disparities by race/ethnicity and socioeconomic status in patients with NSCLC. Additional efforts are needed to assure timely diagnosis and use of effective treatment to lessen these disparities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etnologia , Feminino , Humanos , Cobertura do Seguro/estatística & dados numéricos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/etnologia
13.
Cancer ; 124(10): 2205-2211, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29635808

RESUMO

BACKGROUND: Although cancer drug shortages are a persistent problem in oncology, little is known about the awareness and perspectives of the US population with respect to shortages. METHODS: In 2016, we administered a 13-item cross-sectional survey to 420 respondents who were randomly selected from an online, probability-based sample demographically representative of the adult US population with respect to sex, age, race/ethnicity, education, geography, and income. Analyses applied poststratification sampling weights to draw national inferences. RESULTS: Overall, 16% of respondents reported being aware of drug shortages. Those with a personal history of cancer were more likely to be aware (31% vs 14% [P = .03]). In the overall cohort, most reported wanting to be informed about a substitution due to shortage: 87% and 82% for major or minor differences in efficacy, and 87% and 83% for major or minor differences in side effects. Most also reported they would transfer care to avoid a substitution: 72% for major differences in efficacy, and 61% for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy (all P < .05). CONCLUSION: These data suggest that the US population is largely unaware of cancer drug shortages. Moreover, if being treated for cancer, most people would want to know about drug substitutions, even if it were to result in only minor differences in efficacy or side effects. With more significant differences, many would transfer care. Cancer 2018;124:2205-11. © 2018 American Cancer Society.


Assuntos
Antineoplásicos/provisão & distribução , Substituição de Medicamentos , Medicamentos Genéricos/provisão & distribução , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Estudos Transversais , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/efeitos adversos , Feminino , Alocação de Recursos para a Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
14.
J Natl Cancer Inst ; 110(10): 1059-1066, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29618041

RESUMO

Background: In germline genetic testing, variants from understudied ancestries have been disproportionately classified as being of uncertain significance. We hypothesized that the rate of variant reclassification likewise differs by ancestry. Methods: Nonbenign variants in actionable genes were collected from consenting subjects undergoing genetic testing at two Southern California sites from September 1996 through December 2016. Variant reclassifications were recorded as they were received, until February 2017 or reclassification to benign. Excluding duplicate variants (same ancestry, laboratory, classification), generalized linear models for the hereditary breast cancer genes (BRCA1/2) and other variants investigated whether rate of reclassification differed for seven categories of ancestry compared with non-Hispanic European. Models took into account laboratory, year, gene, sex, and current classification (handled as a time-dependent covariate) and were adjusted for multiple hypothesis testing. Results: Among 1483 nonbenign variants, 693 (46.7%) involved BRCA1/2. Overall, 268 (18.1%) variants were reclassified at least once. Few (9.7%) reclassified variants underwent a net upgrade in pathogenicity. For BRCA1/2 variants, reclassification rates varied by ancestry and increased over time, more steeply for ancestries with lower initial rates (African, Ashkenazi, Chinese) than for ancestries whose initial rates were high (Middle Eastern) or similar to non-Hispanic European (non-Chinese Asian, Native American, Hispanic). In contrast, reclassification rates of non-BRCA1/2 variants did not vary over time but were elevated for most minority ancestries except non-Chinese Asian and Native American. Conclusions: For nonbenign variants in cancer-related genes, the rates at which reclassifications are issued vary by ancestry in ways that differ between BRCA1/2 and other genes.


Assuntos
Predisposição Genética para Doença , Variação Genética , Neoplasias/genética , Grupos Étnicos/genética , Estudos de Associação Genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias/diagnóstico , Neoplasias/mortalidade , Grupos Populacionais/genética , Estudos Prospectivos
15.
J Am Med Inform Assoc ; 25(5): 458-464, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29315417

RESUMO

Objective: Misinterpretation of complex genomic data presents a major challenge in the implementation of precision oncology. We sought to determine whether interactive genomic reports with embedded clinician education and optimized data visualization improved genomic data interpretation. Materials and Methods: We conducted a randomized, vignette-based survey study to determine whether exposure to interactive reports for a somatic gene panel, as compared to static reports, improves physicians' genomic comprehension and report-related satisfaction (overall scores calculated across 3 vignettes, range 0-18 and 1-4, respectively, higher score corresponding with improved endpoints). Results: One hundred and five physicians at a tertiary cancer center participated (29% participation rate): 67% medical, 20% pediatric, 7% radiation, and 7% surgical oncology; 37% female. Prior to viewing the case-based vignettes, 34% of the physicians reported difficulty making treatment recommendations based on the standard static report. After vignette/report exposure, physicians' overall comprehension scores did not differ by report type (mean score: interactive 11.6 vs static 10.5, difference = 1.1, 95% CI, -0.3, 2.5, P = .13). However, physicians exposed to the interactive report were more likely to correctly assess sequencing quality (P < .001) and understand when reports needed to be interpreted with caution (eg, low tumor purity; P = .02). Overall satisfaction scores were higher in the interactive group (mean score 2.5 vs 2.1, difference = 0.4, 95% CI, 0.2-0.7, P = .001). Discussion and Conclusion: Interactive genomic reports may improve physicians' ability to accurately assess genomic data and increase report-related satisfaction. Additional research in users' genomic needs and efforts to integrate interactive reports into electronic health records may facilitate the implementation of precision oncology.


Assuntos
Apresentação de Dados , Genômica , Oncologia , Neoplasias/genética , Medicina de Precisão , Competência Clínica , Compreensão , Feminino , Humanos , Masculino , Análise de Sequência de DNA/métodos
17.
Per Med ; 14(1): 37-50, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28757884

RESUMO

AIM: To understand how a cancer precision medicine tumor board (CPM-TB) made choices about return of results. MATERIALS & METHODS: Observed CPM-TB deliberations and completed in-depth interviews with committee members. RESULTS: Responding to complex evidence of ambiguous significance, deliberations of the CPM-TB were predicated on analytic validity and clinical utility. Members had concerns both about potential harms due to returning results based on weak evidence and about withholding potentially meaningful results. Group dynamics and the clinical experiences of individual committee members shaped their work. CONCLUSION: Both scientific evidence and the social context surrounding deliberations of a CPM-TB influenced decisions about return of results. Subjective elements, while present in any scientific endeavor, may carry more weight in the face of ambiguous findings.

19.
J Oncol Pract ; 13(3): e185-e196, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28095174

RESUMO

PURPOSE: Genomic testing improves outcomes for many at-risk individuals and patients with cancer; however, little is known about how genomic testing for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) is used in clinical practice. PATIENTS AND METHODS: In 2012 to 2013, we surveyed medical oncologists who care for patients in diverse practice and health care settings across the United States about their use of guideline- and non-guideline-endorsed genetic tests. Multivariable regression models identified factors that are associated with greater test use. RESULTS: Of oncologists, 337 completed the survey (participation rate, 53%). Oncologists reported higher use of guideline-endorsed tests (eg, KRAS for CRC; EGFR for NSCLC) than non-guideline-endorsed tests (eg, Onco typeDX Colon; ERCC1 for NSCLC). Many oncologists reported having no patients with CRC who had mismatch repair and/or microsatellite instability (24%) or germline Lynch syndrome (32%) testing, and no patients with NSCLC who had ALK testing (11%). Of oncologists, 32% reported that five or fewer patients had KRAS and EGFR testing for CRC and NSCLC, respectively. Oncologists, rather than pathologists or surgeons, ordered the vast majority of tests. In multivariable analyses, fewer patients in nonprofit integrated health care delivery systems underwent testing than did patients in hospital or office-based single-specialty group settings (all P < .05). High patient volume and patient requests (CRC only) were also associated with higher test use (all P < .05). CONCLUSION: Genomic test use for CRC and NSCLC varies by test and practice characteristics. Research in specific clinical contexts is needed to determine whether the observed variation reflects appropriate or inappropriate care. One potential way to reduce unwanted variation would be to offer widespread reflexive testing by pathology for guideline-endorsed predictive somatic tests.


Assuntos
Neoplasias Colorretais/genética , Genômica/métodos , Neoplasias Pulmonares/genética , Oncologistas/normas , Feminino , Humanos , Masculino
20.
Genet Med ; 19(7): 787-795, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28125075

RESUMO

PURPOSE: Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. METHODS: One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples. Somatic and germ-line alterations were ranked according to therapeutic or clinical relevance. Results were interpreted using an integrated somatic and germ-line framework and returned in accordance with patient preferences. RESULTS: At the time of this analysis, WES had been performed and results returned to the clinical team for 165 participants. Of 768 curated somatic alterations, only 31% were associated with clinical evidence and 69% with preclinical or inferential evidence. Of 806 curated germ-line variants, 5% were clinically relevant and 56% were classified as variants of unknown significance. The variant review and decision-making processes were effective when the process was changed from that of a Molecular Tumor Board to a protocol-based approach. CONCLUSION: The development of novel interpretive and decision-support tools that draw from scientific and clinical evidence will be crucial for the success of cancer precision medicine in WES studies.Genet Med advance online publication 26 January 2017.


Assuntos
Exoma/genética , Medicina de Precisão/métodos , Sequenciamento Completo do Exoma/métodos , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Adulto , Neoplasias Colorretais/genética , Bases de Dados Genéticas , Genômica/métodos , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Pulmonares/genética , Mutação/genética , Estudos Prospectivos , Análise de Sequência de DNA/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA