Patterns of care at the end of life: a retrospective study of Italian patients with advanced breast cancer.

OBJECTIVES: To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death. METHODS: One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected. RESULTS: 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support. CONCLUSIONS: Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy.

Streamlining the diagnostic pathway for Lynch syndrome in colorectal cancer patients: a 10-year experience in a single Italian Cancer Center.

BACKGROUND: Universal screening of colorectal cancer (CRC) patients for Lynch syndrome (LS) through MisMatch Repair (MMR) testing is recommended. BRAF V600E mutation and/or MLH1 promoter methylation (Reflex Testing, RefT)generally rule out LS in MLH1-deficient (dMLH1) patients. We estimated the impact of RefTon genetic counseling (GC) and on the diagnostic yield of genetic testing (GT). METHODS: Overall, 3199 CRC patients were referred to our center between 2011 and 2021. Patients referred until January 2019 (n=2536) underwent universal MMR testing and were termed 'Cohort A'; among patients after February 2019 (n=663), 'Cohort B', RefT was also performed in dMLH1 patients. RESULTS: Overall, 401/3199 patients (12.5%) were MMR-deficient (dMMR); 312 (77.8%) in cohort A and 89 (22.2%) inB; 346/401 were dMLH1 (86.3%), 262/312 (83.9%) in cohort A and 84/89 (94.3%) in B. In Cohort A, 91/312 (29.1%) dMMR patients were referred to GC, 69/91 (75.8%) were in the dMLH1 group; 57/69 (82.6%) dMLH1 patients underwent GT and 1/57 (1.7%) had LS. In Cohort B, 3/84 dMLH1 patients did not undergo BRAF testing. Three BRAF wt and not hypermethylated of the remaining 81 dMLH1 patients were referred to GC and GT, and one had LS. This diagnostic pathway reduced GC referrals by 96% (78/81) in Cohort B and increased the diagnostic yield of GT by about 20 times. CONCLUSION: Our findings support RefT in dMLH1 CRC patients within the LS diagnostic pathway, as it reduces the number of GC sessions needed and increases the diagnostic yield of GT.

Cascade testing in Italian Hereditary Breast Ovarian Cancer families: a missed opportunity for cancer prevention?

Healthy carriers of BRCA1/2 pathogenic variants (PVs) may benefit from risk-reducing measures of proven efficacy. The main approach to identify these individuals is cascade testing, and strategies to support this complex process are under investigation. In Italy, cascade testing has received little attention; therefore, we analyzed the uptake and characteristics of BRCA1/2 cascade testing in families diagnosed with HBOC between 2017 and 2019 at two Italian genetics centers. All blood relatives aged 18 years or older at September 2022 and who could be involved in the first step of cascade testing (i.e., all the living relatives closest to the proband) were included. In addition to first-degree relatives, individuals who were second-, third- or fourth-degree relatives were included if the closest relative(s) was/were deceased. Overall, 213 families were included (103, Genoa; 110, Bologna). Most probands were women affected by breast and/or ovarian cancer (86.4%, Genoa; 84.5%, Bologna), and the branch segregating the PV was known/suspected in 62% of families (62.1%, Genoa; 60.9%, Bologna). Overall, the uptake of cascade testing was 22.8% (25.8%, Genoa; 19.9%, Bologna; OR = 0.59: 95%CI 0.43-0.82). It was strongly associated with female gender (OR = 3.31, 95%CI 2.38-4.59), age ≤ 70 years (< 30 years OR = 3.48, 95%CI 1.85-6.56; 30-70 years OR = 3.08, 95%CI 2.01-4.71), first-degree relationship with the proband (OR = 16.61, 95%CI 10.50-26.28) and segregation of the PV in both the maternal (OR = 2.54, 95%CI 1.72-3.75) and the paternal branch (OR = 4.62, 95%CI 3.09-6.91). These real-world data may be important to inform the design and implementation of strategies aimed at improving the uptake of HBOC cascade testing in Italy.

The CARESSES Randomised Controlled Trial: Exploring the Health-Related Impact of Culturally Competent Artificial Intelligence Embedded Into Socially Assistive Robots and Tested in Older Adult Care Homes.

This trial represents the final stage of the CARESSES project which aimed to develop and evaluate a culturally competent artificial intelligent system embedded into social robots to support older adult wellbeing. A parallel group, single-blind randomised controlled trial was conducted across older adult care homes in England and Japan. Participants randomly allocated to the Experimental Group or Control Group 1 received a Pepper robot for up 18 h across 2 weeks. Two versions of the CARESSES artificial intelligence were tested: a fully culturally competent system (Experimental Group) and a more limited version (Control Group 1). Control Group 2 (Care As Usual) participants did not receive a robot. Quantitative outcomes of interest reported in the current paper were health-related quality of life (SF-36), loneliness (ULS-8), and perceptions of robotic cultural competence (CCATool-Robotics). Thirty-three residents completed all procedures. The difference in SF-36 Emotional Wellbeing scores between Experimental Group and Care As Usual participants over time was significant (F[1] = 6.614, sig = .019, ηp 2 = .258), as was the comparison between Any Robot used and Care As Usual (F[1] = 5.128, sig = .031, ηp 2 = .146). There were no significant changes in SF-36 physical health subscales. ULS-8 loneliness scores slightly improved among Experimental and Control Group 1 participants compared to Care As Usual participants, but this was not significant. This study brings new evidence which cautiously supports the value of culturally competent socially assistive robots in improving the psychological wellbeing of older adults residing in care settings.

Development and Validation of an Italian Adaptation of the Psychosocial Aspects of Hereditary Cancer Questionnaire.

Individuals that attend cancer genetic counseling may experience test-related psychosocial problems that deserve clinical attention. In order to provide a reliable and valid first-line screening tool for these issues, Eijzenga and coworkers developed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire. The aim of this work was to develop an Italian adaptation of the PAHC (I-PACH). This prospective multicenter observational study included three stages: (1) development of a provisional version of the I-PAHC; (2) pilot studies aimed at testing item readability and revising the questionnaire; and (3) a main study aimed at testing the reliability and validity of the final version of the I-PAHC with the administration of a battery comprising measures of depression, anxiety, worry, stress, and life problems to 271 counselees from four cancer genetic clinics. Adapting the original PAHC to the Italian context involved adding two further domains and expanding the emotions domain to include positive emotions. While most of the items were found to be easy to understand and score, some required revision to improve comprehensibility; others were considered irrelevant or redundant and therefore deleted. The final version showed adequate reliability and validity. The I-PAHC provides comprehensive content coverage of cancer genetic-specific psychosocial problems, is well accepted by counselees, and can be considered a sound assessment tool for psychosocial issues related to cancer genetic counseling and risk assessment in Italy.

Sudden shift to remote genetic counseling during the COVID-19 pandemic: Experiences of genetics professionals in Italy.

The 2020 COVID-19 pandemic has rendered in-person provision of genetic counseling impossible for prolonged periods in many countries, mandating a sudden shift to remote delivery. We used qualitative thematic analysis to explore Italian genetics professionals' experience with remote genetic counseling. Fourteen group and four individual interviews were conducted after participants had delivered one or more remote sessions via videoconference or on the telephone. Data were coded and grouped under themes. Three main themes were identified as follows: (a) technical and logistical issues, (b) communication issues, and (c) clinical content and outcome of the session. The participants acknowledged that not having to travel to the clinic saves consultands time and expense. They also highlighted that not sharing a physical space with consultands and having to rely on technology can negatively impact on effective communication, building trusting relationships, and performing accurate psychosocial assessments. Regarding the clinical content of sessions, remote genetic counseling was perceived to favor greater focus and succinct, to the point communication. However, participants also felt uncomfortable not being able to use visual aids to support the explanation of complex concepts. Moreover, demographics and the socio-cultural status of consultands emerged as factors influencing the outcome of remote genetic counseling sessions. Finally, participants reported feeling that more experience with this novel approach would improve their confidence and their ability to adapt their counseling skills as appropriate. Based on these findings, we suggest that effective, equitable provision of remote genetic counseling will require an infrastructure that is able to support video counseling, sharing of clinical documents and visual aids, and connect with a wide range of devices. Moreover, the structure of sessions should be tailored to the specific requirements of remote genetic counseling and suitable training efforts should be promoted to enhance professionals' communication skills.

Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing.

Exome/genome sequencing (ES/GS) is increasingly becoming routine in clinical genetic diagnosis, yet issues regarding how to disclose and manage secondary findings (SFs) remain to be addressed, and limited evidence is available on patients' preferences. We carried out semi-structured interviews with 307 individuals undergoing clinical genetic testing to explore their preferences for return of SFs in the hypothetical scenario that their test would be performed using ES/GS. Participants were 254 females (82.7%) and 53 males (17.3%), aged 18-86 years; 73.9% (81.1% of those with lower education levels) reported no prior knowledge of ES/GS. Prior knowledge of ES/GS was more common among patients tested for Mendelian conditions (34.5%), compared to those undergoing cancer genetic testing (22.3%) or carrier screening (7.4%). Despite this reported lack of knowledge, most participants (213, 69.6%) stated they would prefer to be informed of all possible results. Reasons in favor of disclosure included wanting to be aware of any risks (168; 83.6%) and to help relatives (23; 11.4%), but also hope that preventive measures might become available in the future (10, 5%). Conversely, potential negative impact on quality of life was the commonest motivation against disclosure. Among 179 participants seen for cancer genetic counseling who were interviewed again after test disclosure, 81.9% had not heard about ES/GS in the meantime; however, the proportion of participants opting for disclosure of any variants was lower (116; 64.8%), with 36 (20.1%) changing opinion compared to the first interview. Based on these findings, we conclude that genetic counseling for ES/GS should involve enhanced education and decision-making support to enable informed consent to SFs disclosure.

The CARESSES study protocol: testing and evaluating culturally competent socially assistive robots among older adults residing in long term care homes through a controlled experimental trial.

BACKGROUND: This article describes the design of an intervention study that focuses on whether and to what degree culturally competent social robots can improve health and well-being related outcomes among older adults residing long-term care homes. The trial forms the final stage of the international, multidisciplinary CARESSES project aimed at designing, developing and evaluating culturally competent robots that can assist older people according to the culture of the individual they are supporting. The importance of cultural competence has been demonstrated in previous nursing literature to be key towards improving health outcomes among patients. METHOD: This study employed a mixed-method, single-blind, parallel-group controlled before-and-after experimental trial design that took place in England and Japan. It aimed to recruit 45 residents of long-term care homes aged ≥65 years, possess sufficient cognitive and physical health and who self-identify with the English, Indian or Japanese culture (n = 15 each). Participants were allocated to either the experimental group, control group 1 or control group 2 (all n = 15). Those allocated to the experimental group or control group 1 received a Pepper robot programmed with the CARESSES culturally competent artificial intelligence (experimental group) or a limited version of this software (control group 1) for 18 h across 2 weeks. Participants in control group 2 did not receive a robot and continued to receive care as usual. Participants could also nominate their informal carer(s) to participate. Quantitative data collection occurred at baseline, after 1 week of use, and after 2 weeks of use with the latter time-point also including qualitative semi-structured interviews that explored their experience and perceptions further. Quantitative outcomes of interest included perceptions of robotic cultural competence, health-related quality of life, loneliness, user satisfaction, attitudes towards robots and caregiver burden. DISCUSSION: This trial adds to the current preliminary and limited pool of evidence regarding the benefits of socially assistive robots for older adults which to date indicates considerable potential for improving outcomes. It is the first to assess whether and to what extent cultural competence carries importance in generating improvements to well-being. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.govTrial registration number: NCT03756194.Date of registration: 28 November 2018. URL of trial registry record.

A qualitative study on decision-making about BRCA1/2 testing in Italian women.

OBJECTIVE: In the era of cancer panel testing, new models of genetic counselling providing effective decision-making support are needed. As little is known about Southern European patients' and families' needs and experiences in this regard, we explored Italian women's experiences of clinical BRCA1/2 counselling and testing. METHODS: We interviewed 19 Italian women with a strong family history but no personal history of cancer who had had clinical BRCA1/2 testing. Interviews were recorded and transcribed, and qualitative data were organised into themes. RESULTS: Most respondents had decided to pursue testing before pre-test counselling. Although half the sample reported having reached the decision without thinking through its implications, most participants qualified their choice as unequivocally "the right one." CONCLUSION: A subset of Italian women may arrive at their first cancer genetic consultation having already made a firm decision about testing. To empower women's decision-making, new models of cancer genetic counselling could usefully take into account differences in how they approach the testing process. This includes understanding decision-making from different cultural perspectives. In familistic countries like Italy, for example, decisional support may involve exploring widely shared assumptions regarding responsibilities towards family members and the prioritisation of family over self.

Skin examination behavior: the role of melanoma history, skin type, psychosocial factors, and region of residence in determining clinical and self-conducted skin examination.

OBJECTIVE: To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. DESIGN: A cross-sectional, web-based survey. SETTING: Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL). PARTICIPANTS: A total of 8178 adults from Northern (32%), Central (33%), and Southern (14%) Europe, Australia (13%), and the United States (8%). MAIN OUTCOME MEASURES: Self-reported frequency of skin self-examination (SSE) and clinical skin examination (CSE). RESULTS: After adjustment for age and sex, frequency of skin examination was higher in both Australia (odds ratio [OR]SSE=1.80 [99% CI, 1.49-2.18]; ORCSE=2.68 [99% CI, 2.23-3.23]) and the United States (ORSSE=2.28 [99% CI, 1.76-2.94]; ORCSE=3.39 [99% CI, 2.60-4.18]) than in the 3 European regions combined. Within Europe, participants from Southern Europe reported higher rates of SSE than those in Northern Europe (ORSSE=1.61 [99% CI, 1.31-1.97]), and frequency of CSE was higher in both Central (ORCSE=1.47 [99% CI, 1.22-1.78]) and Southern Europe (ORCSE=3.46 [99% CI, 2.78, 4.31]) than in Northern Europe. Skin examination behavior also varied according to melanoma history: participants with no history of melanoma reported the lowest levels of skin examination, while participants with a previous melanoma diagnosis reported the highest levels. After adjustment for region, and taking into account the role of age, sex, skin type, and mole count, engagement in SSE and CSE was associated with a range of psychosocial factors, including perceived risk of developing melanoma; perceived benefits of, and barriers to, skin examination; perceived confidence in one's ability to engage in screening; and social norms. In addition, among those with no history of melanoma, higher cancer-related worry was associated with greater frequency of SSE. CONCLUSIONS: Given the strong association between psychosocial factors and skin examination behaviors, particularly among people with no history of melanoma, we recommend that greater attempts be made to integrate psycho-education into the fabric of public health initiatives and clinical care, with clinicians, researchers, and advocacy groups playing a key role in guiding individuals to appropriate tools and resources.

MC1R variation and melanoma risk in relation to host/clinical and environmental factors in CDKN2A positive and negative melanoma patients.

Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria.

CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.

Background Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

Predictors of sun protection behaviors and severe sunburn in an international online study.

BACKGROUND: The incidence of melanoma continues to increase in many countries, and primary prevention of melanoma includes avoidance of sunburn as well as adequate sun protection behavior. The aim of this study was to examine the prevalence of self-reported sun protection behaviors and sunburn in users of the Internet, and to identify the demographic, clinical, and attitudinal/motivational correlates of sun protection behaviors. METHODS: Self-report data were gathered on behalf of the GenoMEL consortium using an online survey available in 10 different languages, and 8,178 individuals successfully completed at least 80% of survey items, with 73% of respondents from Europe, 12% from Australia, 7% from the United States, 2% from Israel, and 6% from other countries. RESULTS: Half of all respondents and 27% of those with a previous melanoma reported at least one severe sunburn during the previous 12 months. The strongest factors associated with sun protection behavior were perceived barriers to protection (beta = -0.44/beta = -0.37), and respondents who reported a positive attitude toward suntans were less likely to protect (beta = -0.16/beta = -0.14). Reported use of protective clothing and shade, as well as avoidance of midday sun exposure, were more strongly related to reduced risk of sunburn than sunscreen use. CONCLUSIONS: Despite widespread dissemination of public health messages about the importance of sun protection, a substantial proportion of this international sample, including respondents with a previous melanoma, reported inadequate sun protection behaviors resulting in severe sunburn. IMPACT: Future strategies to decrease sunburn should target the practical, social, and psychological barriers associated with nonuptake of sun protection.

Melanoma risk factors, perceived threat and intentional tanning: an international online survey.

Cutaneous melanoma continues to increase in incidence in many countries, and intentional tanning is a risk factor for melanoma. The aim of this study was to understand how melanoma risk factors, perceived threat and preferences for a suntan relate to intentional tanning. Self-report data were collected on behalf of GenoMEL (www.genomel.org) from the general population using an online survey. A total of 8178 individuals completed the survey, with 72.8% of respondents being from Europe, 12.1% from Australia, 7.1% from the US, 2.5% from Israel and 5.5% from other countries. Seven percent of respondents had previously been diagnosed with melanoma and 8% had at least one first-degree relative with a previous melanoma. Overall, 70% reported some degree of intentional tanning during the past year, and 38% of respondents previously diagnosed with melanoma had intentionally tanned. The total number of risk factors was positively correlated with perceived risk of melanoma [correlation coefficient (rho) = 0.27], and negatively correlated with intentional tanning (rho = -0.16). Preference for a dark suntan was the strongest predictor of intentional tanning [regression coefficient (beta) = 0.35, P<0.001], even in those with a previous melanoma (beta = 0.33, P<0.01). A substantial proportion of participants reported having phenotypic and behavioural risk factors for melanoma. The preference regarding suntans seemed more important in the participants' decision to intentionally tan than their perceived risk of developing melanoma, and this finding was consistent among respondents from different countries. The drive to sunbathe to tan is a key factor to be moderated if melanoma incidence is to be reduced.

Clinical genetic testing for familial melanoma in Italy: a cooperative study.

BACKGROUND: The Italian Society of Human Genetics' (SIGU) recommendations on genetic counseling and testing for hereditary melanoma state that clinical genetic testing can be offered to Italian melanoma families with at least two affected members. OBJECTIVE: In the framework of a cooperative study, we sought to establish the frequency of cyclin-dependent kinase inhibitor 2A mutations in melanoma families that underwent clinical genetic counseling and testing in accordance with the SIGU recommendations at 9 centers in different Italian regions. METHODS: Cyclin-dependent kinase inhibitor 2A testing was conducted by direct sequencing and multiplex ligation-dependent probe amplification analysis in melanoma families with at least two affected members. RESULTS: A total of 33% (68/204) of the families harbored cyclin-dependent kinase inhibitor 2A mutations. In the 145 families with two affected members the mutation frequency was 25%. Three novel mutations, L94P, A86T, and c.407dupG, were identified among the cases and not in 200 controls. LIMITATIONS: We were unable to perform separate analyses for individual centers, as in some cases the number of families was too small. CONCLUSIONS: The availability of clinical genetic testing for melanoma to families with just two affected members in the same branch is justified in Italy in terms of the likelihood of identifying a mutation.

CDKN2A and MC1R analysis in amelanotic and pigmented melanoma.

Amelanotic melanoma (AM) is a rare subtype of melanoma with little or no clinically visible pigment; it is more difficult to diagnose than pigmented melanoma (PM), and has a worse prognosis. In the attempt to find a genetic explanation for the distinction between AM and PM, we conducted a case-case study, matching AM and PM patients, and testing them for germline mutations in high- (p16INK4A, p14ARF, CDK4) and low-penetrance (MC1R) melanoma susceptibility genes. Similar CDKN2A mutations were found in both sets of melanomas. A p14ARF splice germline mutation was detected for the first time in an Italian family with AM. This rare mutation, which has been described only once previously, may be involved in predisposition to the amelanotic phenotype in combination with germline MC1R variants and coordinate somatic expression of pigmentation genes and their regulators.