Evaluation of the Rosa Chatbot Providing Genetic Information to Patients at Risk of Hereditary Breast and Ovarian Cancer: Qualitative Interview Study.

BACKGROUND: Genetic testing has become an integrated part of health care for patients with breast or ovarian cancer, and the increasing demand for genetic testing is accompanied by an increasing need for easy access to reliable genetic information for patients. Therefore, we developed a chatbot app (Rosa) that is able to perform humanlike digital conversations about genetic BRCA testing. OBJECTIVE: Before implementing this new information service in daily clinical practice, we wanted to explore 2 aspects of chatbot use: the perceived utility and trust in chatbot technology among healthy patients at risk of hereditary cancer and how interaction with a chatbot regarding sensitive information about hereditary cancer influences patients. METHODS: Overall, 175 healthy individuals at risk of hereditary breast and ovarian cancer were invited to test the chatbot, Rosa, before and after genetic counseling. To secure a varied sample, participants were recruited from all cancer genetic clinics in Norway, and the selection was based on age, gender, and risk of having a BRCA pathogenic variant. Among the 34.9% (61/175) of participants who consented for individual interview, a selected subgroup (16/61, 26%) shared their experience through in-depth interviews via video. The semistructured interviews covered the following topics: usability, perceived usefulness, trust in the information received via the chatbot, how Rosa influenced the user, and thoughts about future use of digital tools in health care. The transcripts were analyzed using the stepwise-deductive inductive approach. RESULTS: The overall finding was that the chatbot was very welcomed by the participants. They appreciated the 24/7 availability wherever they were and the possibility to use it to prepare for genetic counseling and to repeat and ask questions about what had been said afterward. As Rosa was created by health care professionals, they also valued the information they received as being medically correct. Rosa was referred to as being better than Google because it provided specific and reliable answers to their questions. The findings were summed up in 3 concepts: "Anytime, anywhere"; "In addition, not instead"; and "Trustworthy and true." All participants (16/16) denied increased worry after reading about genetic testing and hereditary breast and ovarian cancer in Rosa. CONCLUSIONS: Our results indicate that a genetic information chatbot has the potential to contribute to easy access to uniform information for patients at risk of hereditary breast and ovarian cancer, regardless of geographical location. The 24/7 availability of quality-assured information, tailored to the specific situation, had a reassuring effect on our participants. It was consistent across concepts that Rosa was a tool for preparation and repetition; however, none of the participants (0/16) supported that Rosa could replace genetic counseling if hereditary cancer was confirmed. This indicates that a chatbot can be a well-suited digital companion to genetic counseling.

Gastric adenocarcinoma and proximal polyposis of the stomach ­ a rare form of hereditary gastric cancer. / Gastrisk adenokarsinom og proksimal ventrikkelpolypose ­ en sjelden form for arvelig magesekkreft.

Hereditary ventricular polyposis in the form of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare condition characterised by a typical distribution of polyps in the stomach and risk of gastric cancer at a young age. Prophylactic gastrectomy may be indicated. The condition is not thought to be associated with increased risk of colon cancer, but the evidence base is limited.

Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants.

BACKGROUND: CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype. METHODS: All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced. RESULTS: Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010). CONCLUSION: Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation.

The PTEN hamartoma tumor syndrome: how oral clinicians may save lives.

INTRODUCTION: Patients with the PTEN hamartoma tumor syndrome (PHTS) have an 81%-90% cumulative lifetime risk of developing cancer. Around 90% of these patients have recognizable oral features. Receiving a diagnosis may save these patients' lives. This is the first presentation of a family with the PHTS diagnosis with focus on the oral and periodontal findings and treatments. CASE PRESENTATION: All three children (one son and two daughters) inherited the same heterozygous variant in the PTEN gene from their father. Gingival overgrowth was observed in all patients in addition to macrocephaly. Other findings included fissured tongue, high arched palate, papules, and trichilemmomas. The father had experienced severe tooth loss. Surgery was performed to treat the gingival overgrowth and periodontal pockets; however, the treatment was characterized by multiple recurrences of the overgrowth. CONCLUSIONS: Oral changes, macrocephaly, tumors, and/or a family history of benign or malignant lesions are important features that oral clinicians should be aware of for a possible PHTS diagnosis. Patients suspected of having PHTS should be referred to a medical practitioner, specifically a geneticist, for further diagnostic investigations. The periodontal problems seemed to be difficult to control for these patients. They will likely need an active and frequent maintenance therapy to control the persistent inflammation and gingival overgrowth. In addition, they need a thorough monitoring for benign or malignant changes in the orofacial regions. Why are these cases new information? Oral features are found in 90% of the cases with the PHTS diagnosis. The periodontal findings showed a persistent recurrence of gingival overgrowth with a strong probability of serious periodontal diseases. What are the keys to successful management of these cases? A suspicion of a PHTS diagnosis with a referral to a medical practitioner, specifically a geneticist, for complete workup may help save these patients' lives. Close monitoring during maintenance therapy with re-treatment as needed to prevent further periodontal complications. Continued monitoring and treatment throughout the patient's lifetime for development of recurrent or new, benign or malignant lesions at relevant sites. What are the primary limitations to success in these cases? A failure to identify the PHTS syndrome with the accompanying oral and periodontal complications. Complications may lead to a delay in appropriate treatment. Inability to control the persistent gingival overgrowth and a deteriorating periodontal condition. A failure to discover benign and malignant lesions in the orofacial region.

Ask Rosa - The making of a digital genetic conversation tool, a chatbot, about hereditary breast and ovarian cancer.

OBJECTIVE: We aimed at developing a pilot version of an app (Rosa) that can perform digital conversations with breast or ovarian cancer patients about genetic BRCA testing, using chatbot technology, to identify best practices for future patient-focused chatbots. METHODS: We chose a commercial chatbot platform and participatory methodology with a team of patient representatives, IT engineers, genetic counselors and clinical geneticists, within a nationwide collaboration. An iterative approach ensured extensive user and formal usability testing during the development process. RESULTS: The development phase lasted for two years until the pilot version was completed in December 2019. The iteration steps disclosed major challenges in the artificial intelligence (AI)-based matching of user provided questions with predefined information in the database, leading initially to high level of fallback answers. We therefore developed strategies to reduce potential language ambiguities (e.g. BRCA1 vs BRCA2) and overcome dialogue confusion. The first prototype contained a database with 500 predefined questions and 67 corresponding predefined answers, while the final version included 2257 predefined questions and 144 predefined answers. Despite the limited AI functionality of the chatbot, the testing revealed that the users liked the layout and found the chatbot trustworthy and reader friendly. CONCLUSIONS: Building a health chatbot is challenging, expensive and time consuming with today's technology. The users had a positive attitude to the chatbot, and would use it in a real life setting, if given to them by health care personnel. PRACTICE IMPLICATIONS: We here present a framework for future health chatbot initiatives. The participatory methodology in combination with an iterative approach ensured that the patient perspective was incorporated at every level of the development process. We strongly recommend this approach in patient-centered health innovations.

Is pharmacogenetic CYP2D6 testing useful?

BACKGROUND: Pharmacogenetic testing is used to uncover genetic causes for variations in drug response. Documentation of the method's usefulness in a clinical setting is scarce. The aim of the study was to systematically categorize the experience from routine CYP2D6 genotyping in a diagnostic laboratory. MATERIAL AND METHODS: All samples submitted to our laboratory for CYP2D6 genotyping in the period 29.06.98-28.12.09 were examined retrospectively. The samples were classified into three indication groups based on clinical information given in the request form. All samples, and a control group consisting of 100 healthy blood donors, were tested for the four most prevalent non-functional CYP2D6 alleles in the European population, and for ultrarapid metabolizer-associated duplications of the gene. RESULTS: 325 samples were included. The proportion of ultrarapid metabolizers was significantly higher in the patient group (4.0 %, p = 0.045) than in the control group (0 %), with the highest proportion among those patients that used a known CYP2D6 substrate. The percentage of poor metabolizers was not significantly higher in the patient group (8.3 %) than in the control group (6.0 %) (p = 0.528). INTERPRETATION: The CYP2D6 analysis could rarely explain the patients' side effects or lack of drug response, even though the study group was selected because of clinical problems due to drugs they were using. Two explanations may be that the indication(s) for genetic testing is not clearly defined and that the CYP2D6 genotype is only one of many factors that determine individual drug response.

Risk reducing mastectomy, breast reconstruction and patient satisfaction in Norwegian BRCA1/2 mutation carriers.

The aim of this study was to evaluate the outcome of risk-reducing mastectomy in BRCA1/2 mutation carriers with and without breast cancer. Uptake, methods of operation and reconstruction, complications, patient satisfaction and histopathological findings were registered at all five departments of genetics in Norway. Data from 267 affected and unaffected BRCA1/2 mutation carriers were analyzed, including a study-specific questionnaire returned by 178 mutation carriers. There was a steady increase in the uptake of risk-reducing mastectomies during the study period. Complications were observed in 106/266 (39.7%) women. Patient satisfaction was high. The majority of women expressed great relief after risk-reducing mastectomy and would have chosen the same option again.