Personalising genetic counselling (POETIC) trial: Protocol for a hybrid type II effectiveness-implementation randomised clinical trial of a patient screening tool to improve patient empowerment after cancer genetic counselling.

BACKGROUND: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling. The aim of this study is to assess the effectiveness and implementation of using the GPRI in improving patient outcomes after genetic counselling and testing for an inherited cancer predisposition. METHODS: The PersOnalising gEneTIc Counselling (POETIC) trial is a hybrid type 2 effectiveness-implementation trial using a randomised control trial to assess the effectiveness of the GPRI in improving patient empowerment (primary outcome), while also assessing implementation from the perspective of clinicians and the healthcare service. Patients referred for a cancer risk assessment to the conjoint clinical genetics service of two metropolitan hospitals in Victoria, Australia, who meet the eligibility criteria and consent to POETIC will be randomised to the usual care or intervention group. Those in the intervention group will complete the GPRI prior to their appointment with the screening results available for the clinicians' use during the appointment. Appointment audio recordings, clinician-reported information about the appointment, patient-reported outcome measures, and clinical data will be used to examine the effectiveness of using the GPRI. Appointment audio recordings, health economic information, and structured interviews will be used to examine the implementation of the GPRI. DISCUSSION: The POETIC trial takes a pragmatic approach by deploying the GPRI as an intervention in the routine clinical practice of a cancer-specific clinical genetics service that is staffed by a multidisciplinary team of genetics and oncology clinicians. Therefore, the effectiveness and implementation evidence generated from this real-world health service setting aims to optimise the relevance of the outcomes of this trial to the practice of genetic counselling while enhancing the operationalisation of the screening tool in routine practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number 12621001582842p. Date of registration: 19th November 2021.

Becoming and being a parent with an inherited predisposition to diffuse gastric cancer: A qualitative study of young adults with a CDH1 pathogenic variant.

PURPOSE: This study explored the experiences of young people with hereditary diffuse gastric cancer (HDGC), an inherited cancer predisposition syndrome, as they navigate becoming and being a parent. DESIGN: We used interpretive description and conducted semi-structured interviews with 13 young Australians (18-39 years) with a CDH1 pathogenic variant (PV). Data were analyzed using team-based, reflexive thematic analysis. FINDINGS: Participants' reproductive decisions centered on the perceived manageability of HDGC, namely via gastrectomy, and timing of their genetic testing. Participants yet to have children and those with challenging gastrectomy experiences favored using reproductive technologies to prevent passing on their PV. Parents who had children before genetic testing described complicated decisions about having more children. Gastrectomy was considered a parental responsibility but recovery diminished parenting abilities. CONCLUSION: Young people with HDGC face unique challenges navigating reproductive decision-making and parenting with gastrectomy. Findings lend credence to calls for longitudinal, developmentally sensitive genetic counseling services.

The Clinical and Psychosocial Outcomes for Women Who Received Unexpected Clinically Actionable Germline Information Identified through Research: An Exploratory Sequential Mixed-Methods Comparative Study.

Background Research identifying and returning clinically actionable germline variants offer a new avenue of access to genetic information. The psychosocial and clinical outcomes for women who have received this 'genome-first care' delivering hereditary breast and ovarian cancer risk information outside of clinical genetics services are unknown. Methods: An exploratory sequential mixed-methods case-control study compared outcomes between women who did (cases; group 1) and did not (controls; group 2) receive clinically actionable genetic information from a research cohort in Victoria, Australia. Participants completed an online survey examining cancer risk perception and worry, and group 1 also completed distress and adaptation measures. Group 1 participants subsequently completed a semi structured interview. Results: Forty-five participants (group 1) and 96 (group 2) completed the online survey, and 31 group 1 participants were interviewed. There were no demographic differences between groups 1 and 2, although more of group 1 participants had children (p = 0.03). Group 1 reported significantly higher breast cancer risk perception (p < 0.001) compared to group 2, and higher cancer worry than group 2 (p < 0.001). Some group 1 participants described how receiving their genetic information heightened their cancer risk perception and exacerbated their cancer worry while waiting for risk-reducing surgery. Group 1 participants reported a MICRA mean score of 27.4 (SD 11.8, range 9−56; possible range 0−95), and an adaptation score of 2.9 (SD = 1.1). Conclusion: There were no adverse psychological outcomes amongst women who received clinically actionable germline information through a model of 'genome-first' care compared to those who did not. These findings support the return of clinically actionable research results to research participants.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

PURPOSE: Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS: In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS: We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION: We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.

Young people's experiences of a CDH1 pathogenic variant: Decision-making about gastric cancer risk management.

The most effective option for gastric cancer risk management in individuals with a CDH1 germline pathogenic or likely pathogenic variant (PV) in Australia is prophylactic total gastrectomy (PTG). There is, however, increasing confidence in endoscopic surveillance as a risk management strategy thus affording individuals with a CDH1 PV with challenging decisions regarding their gastric cancer risk management. For young people, this decision-making comes at a complex development stage of emerging and young adulthood. This study aims to explore the factors that influence young people's decision-making about their gastric cancer risk management due to a CDH1 PV. Potential participants were identified and approached through the Parkville Familial Cancer Centre in Melbourne, Australia. Thematic analysis was used to interpret and analyze the data. Qualitative interviews were conducted with 13 people with a CDH1 PV aged 18 to 39 years, inclusive. The interviews found that participants' familial and shared experiences of cancer and risk management, perceived tolerance of uncertainty, and desire for control over their cancer risk were fundamental in their decision-making about their gastric cancer risk management. The participants' young adult life stage was also deemed particularly important in decisions about the timing of PTG. The findings of this study are vital to inform decisional counseling discussions with this unique population.

Unselected Women's Experiences of Receiving Genetic Research Results for Hereditary Breast and Ovarian Cancer: A Qualitative Study.

Background: Although there is growing consensus that clinically actionable genetic research results should be returned to participants, research on recipients' experiences and best practices for return of research results is scarce. Objective: This study explored how women in a population-based study (lifepool) experience receiving research results about actionable pathogenic variants (PVs) for hereditary breast and ovarian cancer (HBOC) using a two-step notification process with telephone genetic counseling (TGC) support. Methods: We conducted qualitative interviews with lifepool participants with an HBOC PV. We used team-based codebook thematic analysis to develop findings. Findings: Thirty-one women participated (mean age 62.5 years) on average 2.3 years (range 0.3-5.1 years) after result notification. Notification was unexpected but not traumatic and TGC support helped meet women's information and support needs. Notification with referral to a local genetics service empowered women to make informed decisions about personal and familial health. Adaptation to results over time was facilitated by three main processes: seeking information, family communication, and undertaking risk management and/or risk-reducing strategies. Conclusion: Using a two-step notification process to return clinically actionable HBOC PVs from research was well received by women in a population-based study of breast and ovarian cancer susceptibility. Having genetic counseling support with referral to local genetics services in the notification process facilitated women's feelings of empowerment and adaptation to their genetic information over time. These findings build the basis for future methods for the return of actionable genetic research results and population screening.

The art and science of recruitment to a cancer rapid autopsy programme: A qualitative study exploring patient and clinician experiences.

BACKGROUND: CASCADE is a successful, Australia-first cancer rapid autopsy programme. Patients are recruited to the programme by their clinician once they understand that further treatment has only palliative intent. Despite its value, rapid autopsy is a rare research method owing partly to recruitment challenges. AIM: This research aimed to explore (1) how, in practice, clinicians select and recruit patients to the programme and (2) patient experiences of this process. DESIGN: This was a qualitative study grounded in phenomenology. CASCADE team members (clinicians and researchers) and patients participated in semi-structured interviews. Data were analysed using an inductive, team-based approach to thematic analysis. PARTICIPANTS: Interviews were conducted with 31 participants (11 patients and 20 CASCADE team members). RESULTS: Patient selection and recruitment to a rapid autopsy programme is both an art and science. In practice, patient selection is a subjective process that involves assessing a patient's psychosocial suitability for the programme. Trust and rapport are necessary for informing this assessment and to create an environment conducive to discussing rapid autopsy. Clinicians have also crafted their own ways of delivering information about CASCADE, with both clinicians and patients acknowledging that, if not handled sensitively, recruitment could cause distress. Overall, patients were satisfied with the way in which they were recruited. CONCLUSION: Findings provide insight into how clinicians successfully select and recruit patients to a rapid autopsy programme and suggests that discussing such topics are acceptable to end-of-life patients. This research also raises thought-provoking questions about the 'gatekeeping' role of clinicians in recruitment.

Evaluation of telephone genetic counselling to facilitate germline BRCA1/2 testing in women with high-grade serous ovarian cancer.

Systemic healthcare issues and geographical challenges restrict women's access to BRCA1/2 testing to inform the use of tailored treatments for high-grade serous ovarian cancer. Consequently, BRCA1/2 testing in this population is low and improved testing pathways are urgently needed. This study aimed to determine the acceptability and feasibility of telephone genetic counselling (TGC) to facilitate treatment-focused BRCA1/2 testing in Australia for women with high-grade serous ovarian cancer. Women who received TGC were invited to complete a survey examining their experiences of the service. A cost analysis was conducted to compare the service to standard, in-person genetic counselling. One hundred and seven women responded (48% response rate); 8 had a BRCA1/2 variant affecting function. Geographical barriers prevented women from accessing genetic services in the past. All participants had a positive attitude towards testing, and regret following testing was minimal. While the impact of testing was greater for those with a positive test result, overall, genetic testing did not put the additional psychosocial burden on the participants. Participant's evaluations of the telephone interactions with the genetic counsellors were highly satisfactory. The service was also found to be cost-effective. This model of telephone genetic counselling was an acceptable and effective way to reduce barriers to BRCA1/2 testing for women with ovarian cancer.