Core Competencies in Cancer Genomics for Healthcare Professionals: Results From a Systematic Literature Review and a Delphi Process.

The continuous development and use of genomic sequencing requires healthcare professionals to constantly integrate these advancements into their clinical practice. There is a documented lack of cancer genomics contents in the teaching and learning programs. We aimed to identify the core competencies in cancer genomics for non-genetic healthcare professionals. We performed a literature review in PubMed, SCOPUS, and Web of Science databases to retrieve articles published from 2000 to 2018, in English or Italian language. We included articles that reported the competencies for non-genetic healthcare professionals in cancer genomics. A web-based modified Delphi survey was conducted, aiming to define, through consensus, a set of core competencies that should be covered in the curricula. The international expert panel included specialists in genetics, genomics, oncology, and medical specialists. In the literature review, we retrieved nine articles, from which we identified core competencies for general physicians and nurses. The competencies were organized in three main domains: knowledge, attitudes, and practical abilities. In the second round of Delphi survey, consensus of 83.3% was reached for the definition of the core competencies. Thirty-seven items were defined as the competencies required for physicians and forty-two items for nurses. Through a consensus-based approach, a set of core competencies in cancer genomics for non-genetic healthcare professionals has been identified. Our findings could benchmark standards for curriculum development and future educational strategies.

Capacity Building of Health Professionals on Genetics and Genomics Practice: Evaluation of the Effectiveness of a Distance Learning Training Course for Italian Physicians.

BACKGROUND: The rapid spread of personalized medicine requires professionals to manage the "omics revolution." Therefore, the genetics/genomics literacy of healthcare professionals should be in line with the continuous advances in this field, in order to implement its potential implications for diagnosis, control and treatment of diseases. The present study investigates the effectiveness of a distance learning course on genetics and genomics targeted at medical doctors. METHODS: In the context of a project funded by the Italian Ministry of Health, we developed a distance learning course, entitled Genetics and Genomics practice. The course focused on genetic/genomics testing, pharmacogenetics and oncogenomics and was developed according to andragogical training methods (Problem-based Learning and Case-based Learning). We used a pre-test vs. post-test study design to assess knowledge improvement on a set of 10 Multiple Choice Questions (MCQs). We analyzed the proportion of correct answers for each question pre and post-test and the mean score difference stratified by gender, age, professional status and medical discipline. Moreover, the test was submitted to the participants 8 months after the conclusion of the course (follow-up), in order to assess the retained knowledge. RESULTS: The course was completed by 1,637 Italian physicians, most of which were primary care physicians (20.8%), public health professionals (11.5%) and specialist pediatricians (10.6%). The proportion of correct answers increased in the post-test for all the MCQs. The overall mean score significantly increased, from 59.46 in the pre-test to 71.42 in the post-test (p < 0.0001). The comparison in test performance between follow-up and pre-test demonstrated an overall knowledge improvement. CONCLUSION: Genomics literacy among healthcare professionals is essential to ensure optimal translation to healthcare delivery of research. The results of this course suggest that distance-learning training in genetic/genomics practice represents an effective method to improve physicians' knowledge in the immediate and mid-term time scale. A preprint version of this paper is available at: https://www.researchsquare.com/article/rs-10083/v1.

Cost-effectiveness analysis of genetic diagnostic strategies for Lynch syndrome in Italy.

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.

The Current Practice of Lynch Syndrome Diagnosis and Management in Italy: A Qualitative Assessment.

BACKGROUND: Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3-5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy. METHODS: In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as "models" representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved. RESULTS: Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor "screening" was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals. CONCLUSIONS: Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives.

MicroRNAs expression profiles as diagnostic biomarkers of gastric cancer: a systematic literature review.

OBJECTIVE: The early identification of gastric cancer (GC) represents a major clinical challenge. We conducted a systematic review of studies evaluating the miRNA expression profiling as a diagnostic tool in GC. METHODS: We performed a search of PubMed, ISI Web of Science and SCOPUS databases for studies on diagnostic miRNAs and GC, published in English up to October 2017. Eligibility criteria included case-control studies evaluating blood or tissue-based miRNA expression profiles, and incorporating at least two detection phases (screening and validation). RESULTS: We included 27 eligible studies, that reported on 97 deregulated miRNAs either in blood or tissue, out of which 30 were reported in at least two studies. Among 22 studies on tissue-diagnostic miRNAs, 13 consistently upregulated miRNAs (miR-214, miR-21, miR-103, miR-107, miR-196a, miR-196b, miR-7, miR-135b, miR-222, miR-23b, miR-25, miR-92 and miR-93), and six consistently downregulated miRNAs (miR-148a, miR-375, miR-133b, miR-30a, miR-193a and miR-204) were reported. Ten miRNAs with inconsistent direction of expression in tissues were identified. Among the five studies performed on blood samples, only one miRNA was consistently upregulated (miR-20a). CONCLUSIONS: This review shows that some tissue or blood miRNAs may be considered as potential biomarkers for GC diagnosis, that urgently needs to be confirmed from large prospective studies.

A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3-5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS. METHODS: We performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate. RESULTS: We identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%. CONCLUSION: This systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.