Adoption Of Precision Medicine Research Articles

Enhancing Predictive Accuracy for Recurrence-Free Survival in Head and Neck Tumor: A Comparative Study of Weighted Fusion Radiomic Analysis.

Despite advancements in oncology, predicting recurrence-free survival (RFS) in head and neck (H&N) cancer remains challenging due to the heterogeneity of tumor biology and treatment responses. This study aims to address the research gap in the prognostic efficacy of traditional clinical predictors versus advanced radiomics features and to explore the potential of weighted fusion techniques for enhancing RFS prediction. We utilized clinical data, radiomic features from CT and PET scans, and various weighted fusion algorithms to stratify patients into low- and high-risk groups for RFS. The predictive performance of each model was evaluated using Kaplan-Meier survival analysis, and the significance of differences in RFS rates was assessed using confidence interval (CI) tests. The weighted fusion model with a 90% emphasis on PET features significantly outperformed individual modalities, yielding the highest C-index. Additionally, the incorporation of contextual information by varying peritumoral radii did not substantially improve prediction accuracy. While the clinical model and the radiomics model, individually, did not achieve statistical significance in survival differentiation, the combined feature set showed improved performance. The integration of radiomic features with clinical data through weighted fusion algorithms enhances the predictive accuracy of RFS outcomes in head and neck cancer. Our findings suggest that the utilization of multi-modal data helps in developing more reliable predictive models and underscore the potential of PET imaging in refining prognostic assessments. This study propels the discussion forward, indicating a pivotal step toward the adoption of precision medicine in cancer care.

Ethical frameworks of informed consent in the age of pediatric precision medicine.

Precision medicine is an emergent medical paradigm that uses information technology to inform the use of targeted therapies and treatments. One of the first steps of precision medicine involves acquiring the patient's informed consent to protect their rights to autonomous medical decision-making. In pediatrics, there exists mixed recommendations and guidelines of consent-related practices designed to safeguard pediatric patient interests while protecting their autonomy. Here, we provide a high-level, clinical primer of (1) ethical informed consent frameworks widely used in clinical practice and (2) promising modern adaptations to improve informed consent practices in pediatric precision medicine. Given the rapid scientific advances and adoption of precision medicine, we highlight the dual need to both consider the clinical implementation of consent in pediatric precision medicine workflows as well as build rapport with pediatric patients and their substitute decision-makers working alongside interdisciplinary health teams.

Precision Medicine: An Emerging Approach for Patient Care

The philosophy behind contemporary healthcare is that one size fits all. Unfortunately, the outcomes of a standardized treatment regimen are not always uniform. That’s where the concept of precision medicine comes in. According to the Precision Medicine Initiative, precision medicine is “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.” This approach allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people and is in contrast to a one-size-fits-all approach, in which disease treatment and prevention strategies are developed for the average person, with less consideration for the differences between individuals. Although the term “precision medicine” is relatively new, the concept has been a part of healthcare for many years. For example, a person who needs a blood transfusion is not given blood from a randomly selected donor; instead, the donor’s blood type is matched to the recipient to reduce the risk of complications. The adoption of precision medicine will grow because its benefits to healthcare providers and patients are numerous. The highlighting ones are to shift the emphasis in medicine from reaction to prevention, predict susceptibility to disease, improve disease detection, preempt disease progression, customize disease-prevention strategies, prescribe more effective drugs, avoid prescribing drugs with predictable side effects and so on.The goal of precision medicine is to target the right treatments to the right patients at the right time. The short-term goals involve expanding precision medicine in the area of cancer research. Researchers at the National Cancer Institute (NCI) hope to use an increased knowledge of the genetics and biology of cancer to find new, more effective treatments for various forms of this disease. The long-term goals of the Precision Medicine Initiative focus on bringing precision medicine to all areas of health and healthcare on a large scale. Insufficient technologies, limited knowledge, and gaps in research are major obstacles to adding precision medicine to routine clinical care. Advances in precision medicine have already led to powerful new discoveries and FDA-approved treatments that are tailored to specific characteristics of individuals. Patients with a variety of cancers routinely undergo molecular testing as part of patient care, enabling physicians to select treatments that improve chances of survival and reduce exposure to adverse effects. Precision medicine will timely enable clinicians to integrate healthcare data with targeted assays and tests to identify and assess disease biomarkers and risks, determine actionable genetic variants in patients, obtain the entire picture of the metabolome, and map metabolites to disease pathways. Implementof precision medicine as a holistic approach, requires integration of genetic, genomic, clinical, environmental and life-style data using mechanistic models that are complex, and must be built from the ground up. The scientific approach would be to perform analysis of individual genomes giving rise to a new form of preventive and personalised medicine in healthcare. Availability of gene-based designer drugs, precise targeting of molecular fingerprints for disease, appropriate drug therapy, predicting individual susceptibility to disease, diagnosis, and treatment of illness are all a few of the many transformations expected in the decade to come. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 201

Abstract OT-11-01: The informed genetics annotated patient registry: The iGAP registry

Abstract Background Interest and knowledge about the genetics and biology of inherited risk of and progression of disease is growing. Physicians are increasingly using tests and technology, including germline genetic, genomic, and biomarker testing, to provide insight into a healthy individual's risk and an affected individual's disease characteristics, in order to provide personalized clinical management. However, many barriers to adoption of precision medicine still exist in the clinical setting, including rapid advances in technology and research, complex guidelines for eligibility, variable quality and cost, and adequate understanding of appropriate implementation by medical professionals. Methods The iGAP Registry uses an innovative digital platform to collect genetic, genomic, biomarker data and correlates it with clinical, pathologic and outcome data to inform providers of an individual’s risk of developing cancer, guide them to appropriate clinical grade testing and provide clinical decision support to providers for prevention and management strategies over time. The iGAP Registry’s digital platform minimizes technological barriers to longitudinal research participation and is available in mobile and desktop formats, allowing for easy implementation in a wide variety of clinic and hospital settings. The risk tool uses predictive analytics to identify and curate patients at risk who are eligible for initial and further testing. The tool additionally can generate letters of medical necessity, each individualized by personal and family history, for eligibility for genetic testing (based on national guidelines) and additional imaging (based on validated cancer risk calculators). The insights tool provides physicians with decision support on how to interpret and manage abnormal genetic testing results on an individual level and supports improved understanding across lab terminology through variant classification. The insights tool also supplies letters of medical necessity and supporting evidence across many specialties. The platform connects the information stored in the risk and insights tools to a unique participant record and automatically feeds the data into a digital case report form for the research registry. Additional clinical data is entered for patients who consent to be a part of the Registry. This allows for seamless longitudinal data collection over time without disrupting typical clinical workflows, and is further enriched by emailed patient-reported outcomes and physician decision impact questionnaires. Follow-up occurs over 5 years after initial data entry for the 10,000 expected subjects in the Registry (Table 1). Conclusion The iGAP Registry is a multi-center longitudinal, observational research database with an integrated platform of clinically-useful tools designed to address gaps for providers specifically for identifying individuals at elevated risk based on clinical and pathologic factors, guiding them to appropriate genetic, genomic, and biomarker testing and providing clinical insights on actionable results for personalized management and prevention for the individual and their family members over time. The iGAP Registry is currently enrolling and accepting new sites at www.igapregistry.org or https://clinicaltrials.gov/ct2/show/NCT04419896. Table 1: Eligibility CriteriaRetrospective18 years or older;Is/was a patient at participating practice previously tested with germline, genomic, or biomarker tests;For germline patients, have a diagnosis of cancer or P/LP result.Prospective18 years or older;§Presents consecutively to a participating practice and who has previously been screened and tested;Receives/has received germline, genomic, or other biomarker testing, either through a prior provider or a participating practice;Consents to be a part of the registry. Citation Format: Rakesh Patel, Peter Beitsch, Pat Whitworth, Chloe Wernecke, Mary Kay Hardwick. The informed genetics annotated patient registry: The iGAP registry [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-11-01.

Experiences of Latino Participants Receiving Neutral Genomic Screening Results: A Qualitative Study

Purpose: The aim of the study was to characterize experiences of Latino participants receiving genomic screening results. Methods: Participants were recruited at a federally qualified health center in the USA. In-person, semi-structured interviews were conducted in either Spanish or English by a bilingual, bicultural interviewer. Questions focused on motivations for pursuing genomic sequencing, concerns about receiving genomic screening results, and perceived benefits of receiving genomic information. Interviews were audio-recorded, transcribed, and translated. Results: Fifty individuals completed an interview; 39 were conducted in Spanish. Participants described mixed motivations for pursuing genomic screening. Participants viewed the benefits of genomic screening in relation to not only their personal health but to the health of their families and their communities. Participants tended to have few concerns about genomic screening. Those concerns related to potential loss of privacy, misuses of genomic information, and the possibility of receiving distressing results. Some participants had misunderstandings about the scope of the test and the potential implications of their results. Most felt it was better to know about a genetic predisposition to disease than to remain uninformed. Participants felt that genomic screening was worthwhile. Discussion: This is one of the first studies to examine the experiences of Latino individuals receiving genomic screening results. Our results suggest that many Latino patients in the US see value in genomic screening and have limited concerns about its potential to cause harm. These results inform ongoing efforts to increase the availability of genomic medicine to underrepresented populations and add to our understanding of sociocultural drivers in the adoption of precision medicine.

Barriers and facilitators to dissemination and adoption of precision medicine among Hispanics/Latinos

BackgroundWith the rapid advances in gene technologies in recent years, the potential benefits of precision medicine (PM) may spread unevenly to disadvantaged populations, such as Hispanics/Latinos.The objective of this study was to explore patient-level barriers and facilitators to dissemination and adoption of PM among Hispanics/Latinos, including knowledge and awareness.MethodsSelf-identified Hispanics/Latinos from diverse countries in Latin America (N = 41) participated in the study. Using a cross-sectional observational qualitative research design, six focus groups and a demographic questionnaire were collected in English and Spanish. Qualitative content analysis was utilized to code the transcripts and identify emerging themes.ResultsHispanics/Latinos never heard of and had no knowledge about PM. Barriers to dissemination and adoption of PM included lack of health insurance, financial burden, participants’ immigration status, distrust of government, limited English proficiency, low literacy levels, cultural norms, fear about genetic testing results, lack of transportation, newness of PM, and lack of information about PM. Facilitators included family support; information provided in Spanish; use of plain language and graphics; assistance programs for uninsured; trust in physicians, healthcare staff, well-known hospitals, academic institutions, and health care providers and community organization as sources of reliable information; personal motivation, and altruism or societal benefit.ConclusionsCulturally-and linguistically-tailored, low-literacy educational material about PM should be created in English and Spanish. Future research should examine provider-level and system-level barriers and facilitators to implementation and adoption of PM among Hispanic/Latino patients.

Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial.

About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whether patients with pancreatic cancer whose tumours harboured such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy. In this retrospective analysis, treatment history and longitudinal survival outcomes were analysed in patients aged 18 years or older with biopsy-confirmed pancreatic cancer of any stage, enrolled in the KYT programme and who received molecular testing results. Since the timing of KYT enrolment varied for each patient, the primary outcome measurement of median overall survival was calculated from the initial diagnosis of advanced disease until death. We compared median overall survival in patients with actionable mutations who were treated with a matched therapy versus those who were not treated with a matched therapy. Of 1856 patients with pancreatic cancer who were referred to the KYT programme between June 16, 2014, and March 31, 2019, 1082 (58%) patients received personalised reports based on their molecular testing results. Actionable molecular alterations were identified in 282 (26%) of 1082 samples. Among 677 patients for whom outcomes were available, 189 had actionable molecular alterations. With a median follow-up of 383 days (IQR 214-588), those patients with actionable molecular alterations who received a matched therapy (n=46) had significantly longer median overall survival than did those patients who only received unmatched therapies (n=143; 2·58 years [95% CI 2·39 to not reached] vs 1·51 years [1·33-1·87]; hazard ratio 0·42 [95% CI 0·26-0·68], p=0·0004). The 46 patients who received a matched therapy also had significantly longer overall survival than the 488 patients who did not have an actionable molecular alteration (2·58 years [95% CI 2·39 to not reached] vs 1·32 years [1·25-1·47]; HR 0·34 [95% CI 0·22-0·53], p<0·0001). However, median overall survival did not differ between the patients who received unmatched therapy and those without an actionable molecular alteration (HR 0·82 [95% CI 0·64-1·04], p=0·10). These real-world outcomes suggest that the adoption of precision medicine can have a substantial effect on survival in patients with pancreatic cancer, and that molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway warrant further prospective evaluation. Pancreatic Cancer Action Network and Perthera.

Patient-Derived Xenograft Models in Urological Malignancies: Urothelial Cell Carcinoma and Renal Cell Carcinoma.

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models.

Examining Users’ Adoption of Precision Medicine: The Moderating Role of Medical Technical Knowledge

Precision medical technologies have received a great deal of attention, but promoting such technologies remains a problem for enterprises and medical institutions. Adopting the unified theory of acceptance and use of technology (UTAUT) model and the health belief model (HBM), this study investigated the key factors affecting users’ willingness to adopt precision medicine (PM) in terms of technical factors and external stimuli. Based on 415 questionnaires, performance expectancy, price value, social influence, and perceived threat of disease were found to significantly increase users willingness to adopt PM; meanwhile, privacy risks had the opposite effect. Knowledge about PM was found to strengthen the positive effect of performance expectancy, price value, social influence, and perceived threat of disease on willingness to adopt PM and weaken the negative effect of privacy risk. This study demonstrates the successful application of UTAUT to the medical field while also providing guidance for the promotion of PM.

Demand for Precision Medicine: A Discrete-Choice Experiment and External Validation Study.

A limited evidence base and lack of clear clinical guidelines challenge healthcare systems' adoption of precision medicine. The effect of these conditions on demand is not understood. This research estimated the public's preferences and demand for precision medicine outcomes. A discrete-choice experiment survey was conducted with an online sample of the US public who had recent healthcare experience. Statistical analysis was undertaken using an error components mixed logit model. The responsiveness of demand in the context of a changing evidence base was estimated through the price elasticity of demand. External validation was examined using real-world demand for the 21-gene recurrence score assay for breast cancer. In total, 1124 (of 1849) individuals completed the web-based survey. The most important outcomes were survival gains with statistical uncertainty, cost of testing, and medical expert agreement on changing care based on test results. The value ($US, year 2017 values) for a test where most (vs. few) experts agreed to changing treatment based on test results was $US1100 (95% confidence interval [CI] 916-1286). Respondents were willing to pay $US265 (95% CI 46-486) for a test that could result in greater certainty around life-expectancy gains. The predicted demand of the assay was 9% in 2005 and 66% in 2014, compared with real-world uptake of 7% and 71% (root-mean-square prediction error 0.11). Demand was sensitive to price (1% increase in price resulted in > 1% change in demand) when first introduced and insensitive to price (1% increase in price resulted in < 0.1% change in demand) as the evidence base became established. Evidence of external validity was found. Demand was weak and responsive to price in the near term because of uncertainty and an immature evidence base. Clear communication of precision medicine outcomes and uncertainty is crucial in allowing healthcare to align with individual preferences.

Precision medicine in Thailand

Extraordinary advances in high throughput next generation sequencing (NGS) technology and bioinformatics are the main thrust that transforms the current state of healthcare into the era of precision medicine where clinical practice takes individual variability into account. Here, we summarize the current status of the infrastructure we have and the adoption of precision medicine in Thailand in four spheres: rare diseases, oncology, pharmacogenomics, and noncommunicable diseases. Moreover, we provide our perspectives to the future of precision medicine in Thailand, especially the manpower and ethical, legal, and social issues. We believe that with decreasing costs of NGS, increasing ability to interpret the genomic data, a greater number of actionable and available treatments, implementation of precision medicine at the public health level is not a matter of if but when.

Real-world genetic testing patterns in metastatic colorectal cancer: Balancing adoption challenges with performance efficiency.

46 Background: Evaluation of real-world data regarding genetic testing for metastatic colorectal cancer (mCRC) highlights the successes and challenges of precision medicine. Guidelines recommend genetic testing to inform mCRC treatment choice. However, there is a lack of real-world evidence regarding genetic testing patterns, including adoption and efficiency. Methods: This retrospective analysis identified adult patients with newly diagnosed mCRC (2015-2106), Medicare Advantage coverage with a pharmacy benefit (MAPD), and claims evidence of CRC-related genetic testing. Inclusion required diagnosis of colon/rectal cancer on ≥2 medical claims and new metastatic disease. Paid and unpaid claims identified genetic testing, which was classified as limited RAS, extended KRAS/NRAS, limited + extended, and BRAF. Efficiency was measured as time-to-testing and time-to-treatment once testing was performed. Results: The study included 4,408 patients with mCRC and MAPD, with a median age of 72 years. Evidence of limited +/- extended testing was noted for 667 (15.1%) of patients. Of these, 78.3% initiated CRC treatment. Limited, extended, and limited + extended testing was observed for 51.7%, 4.5% and 43.8% of patients, respectively. BRAF was observed for 46.4%, 23.3% and 63.7% of patients with limited, extended, or limited + extended testing, respectively. For the 69.2% of patients tested prior to treatment, the median number of days between mCRC diagnosis and first genetic test was 6 [range: 0-31] days, with 25 [13-46] days between testing and treatment. When treatment preceded testing, the median number of days from treatment to test was 72.0 [20-251]. Of patients with &gt; 1 genetic test, most patients had all tests on the same day (96.9%) or within 7 days (97.8%) of diagnosis, with no differences by type of testing. Conclusions: Per guidelines, mCRC-related genetic testing was completed efficiently after diagnosis and prior to treatment initiation for most patients. Genetic testing rates remain low, perhaps indicating barriers to scaling precision medicine. Ongoing research to explore ways to expedite adoption of precision medicine, while maintaining its efficiency, is needed.

Strategies For Clinical Implementation: Precision Oncology At Three Distinct Institutions.

Despite rapid advances in molecular diagnostics and targeted therapeutics, the adoption of precision medicine into clinical oncology workflows has been slow. Questions about clinical utility, inconsistent reimbursement for molecular diagnostics, and limited access to targeted therapies are some of the major hurdles that have hampered clinical adoption. Despite these challenges, providers have invested in precision medicine programs in an ongoing search for innovative care models to deliver improved patient outcomes and achieve economic gains. We describe the precision oncology medicine programs implemented by an integrated delivery system, a community care center, and an academic medical center, to demonstrate the approaches and challenges associated with clinical implementation efforts designed to advance this treatment paradigm. Payer policies that include coverage for broad genomic testing panels would support the broader application of precision medicine, deepen research benefits, and bring targeted therapies to more patients with advanced cancer.

Precision medicine for disease modification in Parkinson disease.

In this Perspectives article, Espay and colleagues argue that that the adoption of precision medicine in Parkinson disease will require a revision of biomarker development efforts, with the ultimate goal of testing putative disease-modifying interventions in well-defined disease subgroups.

A Framework for Prioritizing Research Investments in Precision Medicine.

The adoption of precision medicine (PM) has been limited in practice to date, and yet its promise has attracted research investments. Developing foundational economic approaches for directing proper use of PM and stimulating growth in this area from multiple perspectives is thus quite timely. Building on our previously developed expected value of individualized care (EVIC) framework, we conceptualize new decision-relevant metrics to better understand and forecast the expected value of PM. Several aspects of behavior at the patient, physician, and payer levels are considered that can inform the rate and manner in which PM innovations diffuse throughout the relevant population. We illustrate this framework and the methods using a retrospective evaluation of the use of OncotypeDx genomic test among breast cancer patients. The enriched metrics can help inform many facets of PM decision making, such as evaluating alternative reimbursement levels for PM tests, implementation and education programs for physicians and patients, and decisions around research investments by manufacturers and public entities. We replicated prior published results on evaluation of OncotypeDx among breast cancer patients but also illustrated that those results are based on assumptions that are often not met in practice. Instead, we show how incorporating more practical aspects of behavior around PM could lead to drastically different estimates of value. We believe that the framework and the methods presented can provide decision makers with more decision-relevant tools to explore the value of PM. There is a growing recognition that data on adoption is important to decision makers. More research is needed to develop prediction models for potential diffusion of PM technologies.

PRM263 - A Framework for Prioritizing Research Investments in Precision Medicine

Introduction. The adoption of precision medicine (PM) has been limited in practice to date, and yet its promise has attracted research investments. Developing foundational economic approaches for directing proper use of PM and stimulating growth in this area from multiple perspectives is thus quite timely. Methods. Building on our previously developed expected value of individualized care (EVIC) framework, we conceptualize new decision-relevant metrics to better understand and forecast the expected value of PM. Several aspects of behavior at the patient, physician, and payer levels are considered that can inform the rate and manner in which PM innovations diffuse throughout the relevant population. We illustrate this framework and the methods using a retrospective evaluation of the use of OncotypeDx genomic test among breast cancer patients. Results. The enriched metrics can help inform many facets of PM decision making, such as evaluating alternative reimbursement levels for PM tests, implementation and ...