Reducing Loneliness and Social Isolation of Older Adults Through Voice Assistants: Literature Review and Bibliometric Analysis.

BACKGROUND: Loneliness and social isolation are major public health concerns for older adults, with severe mental and physical health consequences. New technologies may have a great impact in providing support to the daily lives of older adults and addressing the many challenges they face. In this scenario, technologies based on voice assistants (VAs) are of great interest and potential benefit in reducing loneliness and social isolation in this population, because they could overcome existing barriers with other digital technologies through easier and more natural human-computer interaction. OBJECTIVE: This study aims to investigate the use of VAs to reduce loneliness and social isolation of older adults by performing a systematic literature review and a bibliometric cluster mapping analysis. METHODS: We searched PubMed, Embase, and Scopus databases for articles that were published in the last 6 years, related to the following main topics: voice interface, VA, older adults, isolation, and loneliness. A total of 40 articles were found, of which 16 (40%) were included in this review. The included articles were then assessed through a qualitative scoring method and summarized. Finally, a bibliometric analysis was conducted using VOSviewer software (Leiden University's Centre for Science and Technology Studies). RESULTS: Of the 16 articles included in the review, only 2 (13%) were considered of poor methodological quality, whereas 9 (56%) were of medium quality and 5 (31%) were of high quality. Finally, through bibliometric analysis, 221 keywords were extracted, of which 36 (16%) were selected. The most important keywords, by number of occurrences and by total link strength; results of the analysis with the Association Strength normalization method; and default values were then presented. The final bibliometric network consisted of 36 selected keywords, which were grouped into 3 clusters related to 3 main topics (ie, VA use for social isolation among older adults, the significance of age in the context of loneliness, and the impact of sex factors on well-being). For most of the selected articles, the effect of VA on social isolation and loneliness of older adults was a minor theme. However, more investigations were done on user experience, obtaining preliminary positive results. CONCLUSIONS: Most articles on the use of VAs by older adults to reduce social isolation and loneliness focus on usability, acceptability, or user experience. Nevertheless, studies directly addressing the impact that using a VA has on the social isolation and loneliness of older adults find positive and promising results and provide important information for future research, interventions, and policy development in the field of geriatric care and technology.

Results of the Italian RESILIEN-T Pilot Study: A Mobile Health Tool to Support Older People with Mild Cognitive Impairment.

(1) Background: The RESILIEN-T system addresses the need for innovative solutions to support self-management in older people with Mild Cognitive Impairment (MCI). Despite the increasing prevalence of dementia and MCI, there is a lack of tailored solutions for these individuals. The RESILIEN-T system aims to empower and engage people with cognitive decline by providing a modular platform for self-management and coaching services. (2) Methods: Italian data collected for the RESILIEN-T project involved 62 older participants randomly assigned to the intervention or control group. Data were collected through questionnaires and user interactions with the system over a three-month period. (3) Results: Quantitative outcomes showed no significant differences between the intervention and control groups, except for an improvement in perceived memory capability in the intervention group. The usability assessment indicated a high level of acceptance of the RESILIEN-T system. (4) Discussions: Although no significant improvements were observed in most quantitative measures, the high user engagement and acceptance suggest the potential effectiveness of the RESILIEN-T system. Future improvements could involve integrating smart objects and interactive virtual agents. Overall, RESILIEN-T represents a promising step toward empowering individuals with cognitive impairment in their self-management and decision-making processes.

Correction: Technology-Assisted Cognitive Motor Dual-Task Rehabilitation in Chronic Age-Related Conditions: Systematic Review.

[This corrects the article DOI: 10.2196/44484.].

Technology-Assisted Cognitive Motor Dual-Task Rehabilitation in Chronic Age-Related Conditions: Systematic Review.

BACKGROUND: Cognitive-motor dual-task (CMDT) is defined as the parallel processing of motor (eg, gait) and cognitive (eg, executive functions) activities and is an essential ability in daily life. Older adults living with frailty, chronic conditions (eg, neurodegenerative diseases), or multimorbidity pay high costs during CMDT. This can have serious consequences on the health and safety of older adults with chronic age-related conditions. However, CMDT rehabilitation can provide useful and effective therapies for these patients, particularly if delivered through technological devices. OBJECTIVE: This review aims to describe the current technological applications, CMDT rehabilitative procedures, target populations, condition assessment, and efficacy and effectiveness of technology-assisted CMDT rehabilitation in chronic age-related conditions. METHODS: We performed this systematic review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, on 3 databases (Web of Science, Embase, and PubMed). Original articles that were published in English; involved older adults (>65 years) with ≥1 chronic condition and/or frailty; and tested, with a clinical trial, a technology-assisted CMDT rehabilitation against a control condition were included. Risk of bias (Cochrane tool) and the RITES (Rating of Included Trials on the Efficacy-Effectiveness Spectrum) tool were used to evaluate the included studies. RESULTS: A total of 1097 papers were screened, and 8 (0.73%) studies met the predefined inclusion criteria for this review. The target conditions for technology-assisted CMDT rehabilitation included Parkinson disease and dementia. However, little information regarding multimorbidity, chronicity, or frailty status is available. The primary outcomes included falls, balance, gait parameters, dual-task performance, and executive functions and attention. CMDT technology mainly consists of a motion-tracking system combined with virtual reality. CMDT rehabilitation involves different types of tasks (eg, obstacle negotiation and CMDT exercises). Compared with control conditions, CMDT training was found to be pleasant, safe, and effective particularly for dual-task performances, falls, gait, and cognition, and the effects were maintained at midterm follow-up. CONCLUSIONS: Despite further research being mandatory, technology-assisted CMDT rehabilitation is a promising method to enhance motor-cognitive functions in older adults with chronic conditions.

Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma.

Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting. Differential mass spectrometry studies were performed on 14 serum samples from patients with heavily pretreated platinum-resistant ovarian cancer who received the FOLFOX-4 regimen as a salvage therapy. The serum was analyzed at baseline time (T0) before FOLFOX-4 treatment, and before the second cycle of treatment (T1), with the aim of understanding if it was possible, after a first treatment cycle, to detect significant proteome changes that could be associated with patients responses to therapy. A total of 291 shared expressed proteins was identified and 12 proteins were finally selected between patients who attained partial response or no-response to chemotherapy when both response to therapy and time dependence (T0, T1) were considered in the statistical analysis. The protein panel included APOL1, GSN, GFI1, LCATL, MNA, LYVE1, ROR1, SHBG, SOD3, TEC, VPS18, and ZNF573. Using a bioinformatics network enrichment approach and metanalysis study, relationships between serum and cellular proteins were identified. An analysis of protein networks was conducted and identified at least three biological processes with functional and therapeutic significance in ovarian cancer, including lipoproteins metabolic process, structural component modulation in relation to cellular apoptosis and autophagy, and cellular oxidative stress response. Five proteins were almost independent from the network (LYVE1, ROR1, TEC, GFI1, and ZNF573). All proteins were associated with response to drug-resistant ovarian cancer resistant and were mechanistically connected to the pathways associated with cancer arrest. These results can be the basis for extending a biomarker discovery process to a clinical trial, as an early predictive tool of chemo-response to FOLFOX-4 of heavily treated ovarian cancer patients and for supporting the oncologist to continue or to interrupt the therapy.

A Technology-Based Intervention to Support Older Adults in Living Independently: Protocol for a Cross-National Feasibility Pilot.

Innovative technologies can support older adults with or without disabilities, allowing them to live independently in their environment whilst monitoring their health and safety conditions and thereby reducing the significant burden on caregivers, whether family or professional. This paper discusses the design of a study protocol to evaluate the acceptance, usability, and efficiency of the SAVE system, a custom-developed information technology-based elderly care system. The study will involve older adults (aged 65 or older), professional and lay caregivers, and care service decision-makers representing all types of users in a care service scenario. The SAVE environmental sensors, smartwatches, smartphones, and Web service application will be evaluated in people's homes situated in Romania, Italy, and Hungary with a total of 165 users of the three types (cares, elderly, and admin). The study design follows the mixed method approach, using standardized tests and questionnaires with open-ended questions and logging all the data for evaluation. The trial is registered to the platform ClinicalTrials.gov with the registration number NCT05626556. This protocol not only guides the participating countries but can be a feasibility protocol suitable for evaluating the usability and quality of similar systems.

An integrated intervention of computerized cognitive training and physical exercise in virtual reality for people with Alzheimer's disease: The jDome study protocol.

Introduction: Alzheimer's disease is a neurodegenerative syndrome characterized by cognitive deficits, loss of daily functions, and mental and behavioral disorders, which cause stress and negatively affect the quality of life. Studies in the field suggest that combining cognitive training with physical activity can reduce the risk of developing the disease and, once neurodegeneration has begun, it slows its progress. In particular, virtual reality and augmented reality administer cognitive stimulation while providing a link to autobiographical memory through reminiscence, enabling the improvement of the person's quality of life. The present protocol aims to evaluate the effectiveness of cognitive and physical treatments, integrated with the addition of virtual reality and reminiscence elements, using the Brainer software, in which people will find cognitive training, and the jDome® BikeAround™ system, which will allow participants to pedal along a personalized path projected on a schematic, using an exercise bike connected to the system. Methods and analysis: For this study, 78 patients with mild Alzheimer's dementia were recruited and divided into the Experimental Group (EG) and Control Group (CG). Sixteen treatment sessions of 60 min each were conducted for both groups (2 training sessions per week, for 8 weeks), including 1 patient at a time. The EG received cognitive treatment with Brainer and physical training with jDome, while the CG received cognitive treatment with Brainer and physical training with a classic bicycle. The evaluation mainly focused on the assessment of the person's cognitive status. Other analyses were conducted on the quality of life, mood, behavioral disorders, and physical function, which were considered secondary outcomes. Discussions: The ultimate goal of the present study is to test the effectiveness of a treatment for people with mild Alzheimer's focused on the integration of cognitive training and aerobic physical activity, using an exercise bike, with the addition of virtual reality and reminiscence elements. Ethics and dissemination: The study was approved by the Ethics Committee of the IRCCS INRCA. It was recorded in ClinicalTrials.gov on 2 June 2022 with the number NCT05402423. The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.

Toward the Integration of Technology-Based Interventions in the Care Pathway for People with Dementia: A Cross-National Study.

BACKGROUND: The integration of technology-based interventions into health and care provision in our aging society is still a challenge especially in the care pathway for people with dementia. OBJECTIVE: The study aims to: (1) identify which socio-demographic characteristics are independently associated with the use of the embodied conversational agent among subjects with dementia, (2) uncover patient cluster profiles based on these characteristics, and (3) discuss technology-based interventions challenges. METHODS: A virtual agent was used for four weeks by 55 persons with dementia living in their home environment. RESULTS: Participants evaluated the agent as easy-to-use and quickly learnable. They felt confident while using the system and expressed the willingness to use it frequently. Moreover, 21/55 of the patients perceived the virtual agent as a friend and assistant who they could feel close to and who would remind them of important things. CONCLUSIONS: Technology-based interventions require a significant effort, such as personalized features and patient-centered care pathways, to be effective. Therefore, this study enriches the open discussion on how such virtual agents must be evidence-based related and designed by multidisciplinary teams, following patient-centered care as well as user-centered design approaches.

Melphalan as a Promising Treatment for BRCA-Related Ovarian Carcinoma.

INTRODUCTION: Melphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response to melphalan in patients with recurrent EOC after platinum-based therapy. MATERIAL AND METHODS: This retrospective observational study included patients with recurrent EOC treated with melphalan between February 2007 to July 2020. Eligibility criteria included having a histological confirmation of EOC, previous treatment with carboplatin plus paclitaxel regimens, and disease recurrence during treatment with or within 6 months of the end of the platinum-based chemotherapy. RESULTS: A total of 75 platinum-resistant EOC patients were enrolled. Median age was 69 years (range 41-82). Median of previous therapies before melphalan was 4 (range 1-7). We observed a median follow-up of 32 months (range 1-62), progression-free survival (PFS) and overall survival (OS) of 3.6 months (range 2.9-4.7) and 9.5 months (range 8.0-14.1), respectively. In the whole population, 1 complete response, 6 partial responses and 37 stable diseases were registered with an overall clinical benefit rate of 58.7%. In BRCA1/2 mutant patients, we showed a significant longer PFS compared to BRCA1/2 wild type patients (6.2 versus 2.6 months; hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.10-0.61; p=0.002). Moreover, a trend was seen for BRCA1/2 mutants to have a better OS (25.9 versus 8.0 months; HR 0.38; 95% CI 0.12-1.19; p=0.097). CONCLUSIONS: Our study represents the largest cohort of heavily-pretreated EOC patients receiving melphalan treatment. Here, we report a considerable clinical activity of melphalan chemotherapy, more evident in a subset of BRCA1/2 mutated patients. Prospective studies to validate these findings are warranted.

Embodied Conversational Agents for Patients With Dementia: Thematic Literature Analysis.

BACKGROUND: As the world's population rapidly ages, the number of older adults with cognitive impairment will also increase. Several studies have identified numerous complex needs of people with dementia, which assistive technologies still fail to support. Recent trends have led to an increasing focus on the use of embodied conversational agents (ECAs) as virtual entities able to interact with a person through natural and familiar verbal and nonverbal communication. The use of ECAs could improve the accessibility and acceptance of assistive technologies matching those high-level needs that are not well covered to date. OBJECTIVE: The aim of this thematic literature analysis was to map current studies in the field of designing ECAs for patients with dementia in order to identify the existing research trend and possible gaps that need to be covered in the near future. The review questions in this study were as follows: (1) what research frameworks are used to study the interaction between patients with dementia and ECAs? (2) what are the findings? and (3) what are the barriers reported in these studies? METHODS: Separate literature searches were conducted in PubMed, Web of Science, Scopus, and Embase databases by using specific umbrella phrases to target the population (patients with dementia) and the technology-based intervention (embodied conversational agent). Studies that met the inclusion criteria were appraised through the Mixed Methods Appraisal Tool and then discussed in a thematic analysis. RESULTS: The search process identified 115 records from the databases and study references. After duplicates (n=45) were removed, 70 papers remained for the initial screening. A total of 7 studies were finally included in the qualitative synthesis. A thematic analysis of the reviewed studies identified major themes and subthemes: the research frameworks used to gather users' perspectives on ECAs (theme 1), the insights shared by the 7 studies as well as the value of user involvement in the development phases and the challenge of matching the system functionalities with the users' needs (theme 2), and the main methodological and technical problems faced by each study team (theme 3). CONCLUSIONS: Our thematic literature analysis shows that the field of ECAs is novel and poorly discussed in the scientific community and that more sophisticated study designs and proofs of efficacy of the approach are required. Therefore, by analyzing the main topic of the narrative review, this study underscores the challenge of synchronizing and harmonizing knowledge, efforts, and challenges in the dementia care field and its person-centered paradigm through the user-centered design approach. Enabling strict collaboration between interdisciplinary research networks, medical scientists, technology developers, patients, and their formal and informal caregivers is still a great challenge in the field of technologies for older adults.

A Qualitative Study toward Technologies for Active and Healthy Aging: A Thematic Analysis of Perspectives among Primary, Secondary, and Tertiary End Users.

It is expected that, by 2050, people aged over 60 in 65 nations will constitute 30% of the total population. Healthy aging is at the top of the world political agenda as a possible means for hindering the collapse of care systems. How can ICT/sensing technology meet older people's needs for active and healthy aging? This qualitative study carried out in Italy and Romania in 2020 involved 30 participants: older adults, caregivers, and stakeholders. Based on a user-centered design approach, this study aimed to understand which requirements of ICT/sensing technologies could match people's needs of active and healthy aging. Findings highlighted that ICT/sensing technology needs to focus on six major themes: (1) learnability, (2) security, (3) independence, empowerment, and coaching values, (4) social isolation, (5) impact of habit, culture, and education variables, and (6) personalized solutions. These themes are consistent with the Active Aging framework and the factors that influence perceived usefulness and potential benefits among older adults. Consequently, this study shows how well-known, but still unresolved, issues affect the field of information and communication technologies (ICTs) to promote active and healthy aging. This suggests that the reinforcement of the public health system, especially considering the pandemic effect, requires a concrete and formidable effort from an interdisciplinary research network.

Usability and Acceptance of the Embodied Conversational Agent Anne by People With Dementia and Their Caregivers: Exploratory Study in Home Environment Settings.

BACKGROUND: Information and communication technologies are tools that are able to support cognitive functions, monitor health and movements, provide reminders to maintain residual memory abilities, and promote social support, especially among patients with dementia. Among these technologies, embodied conversational agents (ECAs) are seen as screen-based entities designed to stimulate human face-to-face conversation skills, allowing for natural human-machine interaction. Unfortunately, the evidence that such agents deliver care benefits in supporting people affected by dementia and their caregivers has not yet been well studied. Therefore, research in this area is essential for the entire scientific community. OBJECTIVE: This study aims to evaluate the usability and acceptability of the virtual agent Anne by people living with dementia. The study is also designed to assess the ability of target users to use the system independently and receive valuable information from it. METHODS: We conducted a 4-week trial that involved 20 older adults living with dementia and 14 family caregivers in home environment settings in Italy. This study used a mixed methods approach, balancing quantitative and qualitative instruments to gather data from users. Telemetry data were also collected. RESULTS: Older users were particularly engaged in providing significant responses and participating in system improvements. Some of them clearly discussed how technical problems related to speech recognition had a negative impact on the intention to use, adaptiveness, usefulness, and trust. Moreover, the usability of the system achieved an encouraging score, and half of the sample recognized a role of the agent Anne. This study confirms that the quality of automatic speech recognition and synthesis is still a technical issue and has room for improvement, whereas the touch screen modality is almost stable and positively used by patients with dementia. CONCLUSIONS: This study demonstrated the ability of target users to use the system independently in their home environment; overall, the involved participants shared good engagement with the system, approaching the virtual agents as a companion able to support memory and enjoyment needs. Therefore, this research provides data that sustain the use of ECAs as future eHealth systems that are able to address the basic and higher-level needs of people living with dementia. This specific field of research is novel and poorly discussed in the scientific community. This could be because of its novelty, yet there is an urgent need to strengthen data, research, and innovation to accelerate the implementation of ECAs as a future method to offer nonpharmacological support to community-dwelling people with dementia.

Post-traumatic stress symptoms in long-term disease-free cancer survivors and their family caregivers.

BACKGROUND: The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post-Traumatic Stress Symptoms (PTSS) in long-term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term. METHODS: In this cross-sectional study 212 survivor-family caregiver dyads completed measures of post-traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects. RESULTS: Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post-traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p < 0.001), whereas among caregivers it was associated with depression and having a closer relationship with patients (p < 0.001). Patients' depression was associated with caregivers' intrusion symptoms. CONCLUSIONS: High levels of cancer-related PTSS were still present several years after treatment in both survivors and caregivers. Psychopathology may derive from complex interactions among coping, previous disorders and between-person dynamics.

Dancing With Parkinson's Disease: The SI-ROBOTICS Study Protocol.

Introduction: Parkinson's disease (PD) is one of the most frequent causes of disability among older people, characterized by motor disorders, rigidity, and balance problems. Recently, dance has started to be considered an effective exercise for people with PD. In particular, Irish dancing, along with tango and different forms of modern dance, may be a valid strategy to motivate people with PD to perform physical activity. The present protocol aims to implement and evaluate a rehabilitation program based on a new system called "SI-ROBOTICS," composed of multiple technological components, such as a social robotic platform embedded with an artificial vision setting, a dance-based game, environmental and wearable sensors, and an advanced AI reasoner module. Methods and Analysis: For this study, 20 patients with PD will be recruited. Sixteen therapy sessions of 50 min will be conducted (two training sessions per week, for 8 weeks), involving two patients at a time. Evaluation will be primarily focused on the acceptability of the SI-ROBOTICS system. Moreover, the analysis of the impact on the patients' functional status, gait, balance, fear of falling, cardio-respiratory performance, motor symptoms related to PD, and quality of life, will be considered as secondary outcomes. The trial will start in November 2021 and is expected to end by April 2022. Discussions: The study aims to propose and evaluate a new approach in PD rehabilitation, focused on the use of Irish dancing, together with a new technological system focused on helping the patient perform the dance steps and on collecting kinematic and performance parameters used both by the physiotherapist (for the evaluation and planning of the subsequent sessions) and by the system (to outline the levels of difficulty of the exercise). Ethics and Dissemination: The study was approved by the Ethics Committee of the IRCCS INRCA. It was recorded in ClinicalTrials.gov on the number NCT05005208. The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.

Potential Application of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Renal Cell Tumors.

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CAR-T cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CAR-T cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CAR-T cell therapy in renal cell malignancies.

Coaching Through Technology: A Systematic Review into Efficacy and Effectiveness for the Ageing Population.

Background: Despite the evidence on the positive role of self-management, the adoption of health coaching strategies for older people is still limited. To address these gaps, recent efforts have been made in the ICT sector in order to develop systems for delivering coaching and overcoming barriers relating to scarcity of resources. The aim of this review is to examine the efficacy of personal health coaching systems for older adults using digital virtual agents. Methods: A systematic review of the literature was conducted in December 2019 analyzing manuscripts from four databases over the last 10 years. Nine papers were included. Results: Despite the low number of studies, there was evidence that technology-integrated interventions can deliver benefits for health over usual care. However, the review raises important questions about how to maintain benefits and permanence of behavior change produced by short-term interventions. Conclusion: These systems offer a potential tool to reduce costs, minimize therapist burden and training, and expand the range of clients who can benefit from them. It is desirable that in the future the number of studies will grow, considering other aspects such as the role of the virtual coaches' characteristics, social-presence, empathy, usability, and health literacy.

Enzalutamide for the treatment of nonmetastatic castration-resistant prostate cancer.

INTRODUCTION: Enzalutamide is the first characterized second-generation nonsteroidal androgen receptor inhibitor (ARi). Its efficacy has been established in several clinical trials evaluating its role in different settings of prostate cancer. Recently, enzalutamide has been approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). AREAS COVERED: In this paper, the authors describe the chemical structure and pharmacologic characteristics of enzalutamide, providing a summary of clinical trials evaluating its efficacy and safety in prostate cancer patients. EXPERT OPINION: Enzalutamide adds to the growing arsenal of ARi used in nmCRPC. An improvement in metastasis-free survival was observed with the use of these new treatment options; recently released preliminary data report also an OS benefit. These novel agents are generally well tolerated, but their safety profiles differ slightly. Since head-to-head comparisons between ARi in nmCRPC are lacking, the adverse events profile, as well as drug availability, costs, and considerations on treatment-sequencing, would most likely influence the selection of the individual agent in this setting. Further research is needed to improve treatment selection and clarify many unsolved issues. Abbreviations ARi: nonsteroidal androgen receptor inhibitor; nmCRPC: nonmetastatic castration resistant prostate cancer; ADT: androgen deprivation therapy; OS: overall survival; PSA: prostate specific antigen; FDA: Food and Drug Administration; AR: Androgen Receptor; MFS: metastasis free survival; PSA-DT: PSA doubling time; HR: hazard ratio; CI: confidence interval; AEs: adverse events; mCRPC: metastatic castration resistant prostate cancer; mHSPC: metastatic hormone-sensitive prostate cancer; rPFS: radiographic progression-free survival; OR: odds ratio.

Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress.

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.

Plasma Androgen Receptor in Prostate Cancer.

The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma AR aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests the potential for using plasma AR as a biomarker for selecting treatment, i.e., hormone therapy or chemotherapy, and the possibility of modulating taxane dose. In recent years, plasma AR status has also been investigated in association with novel agents, such as 177Lu-PSMA radioligand therapy and PARP inhibitors. This review will focus on AR testing in plasma that may have clinical utility for treatment selection in advanced prostate cancer.

Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer.

BACKGROUND: The purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer. METHODS: Clinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients. RESULTS: The median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1-17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3-4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3-4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7-4.9] and 6.2 months (95% CI 2.4-14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan. CONCLUSIONS: The FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.