Developing a risk score using liquid biopsy biomarkers for selecting Immunotherapy responders and stratifying disease progression risk in metastatic melanoma patients Amalia Azzariti, Simona De Summa, Tommaso M. Marvulli, Ivana De Risi, Giuseppe De Palma, et al. Journal of Experimental and Clinical Cancer Research, 2025 Background Despite the high response rate to PD-1 blockade therapy in metastatic melanoma (MM) patients, a significant proportion of patients do not respond. Identifying biomarkers to predict patient response is crucial, ideally through non-invasive methods such as liquid biopsy. Methods Soluble forms of PD1, PD-L1, LAG-3, CTLA-4, CD4, CD73, and CD74 were quantified using ELISA assay in plasma of a cohort of 110 MM patients, at baseline, to investigate possible correlations with clinical outcomes. A clinical risk prediction model was applied and validated in pilot studies. Results No biomarker showed statistically significant differences between responders and non-responders. However, high number of significant correlations were observed among certain biomarkers in non-responders. Through univariate and multivariate Cox analyses, we identified sPD-L1, sCTLA-4, sCD73, and sCD74 as independent biomarkers predicting progression-free survival and overall survival. According to ROC analysis we discovered that, except for sCD73, values of sPD-L1, sCTLA-4, and sCD74 lower than the cut-off predicted lower disease progression and reduced mortality. A comprehensive risk score for predicting progression-free survival was developed by incorporating the values of the two identified independent factors, sCTLA-4 and sCD74, which significantly improved the accuracy of outcome prediction. Pilot validations highlighted the potential use of the risk score in treatment-naive individuals and long responders. Conclusion In summary, risk score based on circulating sCTLA-4 and sCD74 reflects the response to immune checkpoint inhibitor (ICI) therapy in MM patients. If confirmed, through further validation, these findings could assist in recommending therapy to patients likely to experience a long-lasting response.
BRCA cascade counselling and testing in Italy: current position and future directions Silvia Costanzo, Lea Godino, Simona De Summa, Tommaso Maria Marvulli, Maurizio Genuardi, et al. BMC Cancer, 2025 Background Genetic testing has led to a considerable enhancement in the ability to identify individuals at risk of Hereditary Breast and Ovarian Cancer syndrome related to BRCA1/2 pathogenic variants, thus necessitating personalised prevention programs. However, barriers related to intrafamilial communication, privacy regulations, and genetic information dissemination hinder preventive care, particularly in Italy, where legal constraints limit the disclosure of genetic risks to at-risk relatives. This study examines the relationship between BRCA1/2 carriers’ communication challenges and three factors: cancer status, comprehension of genetic information, and the genetic counseling pathway accessed (Traditional Genetic Counseling, TGC vs. Mainstream Cancer Genetics, MCG). Methods This multicenter, prospective, observational study included 277 BRCA1/2 carriers (probands and relatives) aged 18–80 from various Italian centers. Participants completed a sociodemographic form, a self-administered survey, and psychological assessments (Impact of Event Scale, IES and Distress Thermometer, DT). Categorical variables were compared using Pearson’s Chi-squared test or Fisher’s exact test based on sample size and expected frequencies, whereas continuous variables were analyzed using the Wilcoxon rank-sum test because of non-normal data distribution. Results Among the 277 carriers (115 probands, 162 relatives), 79.4% received TGC and 20.6% MCG. The cancer prevalence was higher in probands (83%) than in relatives (22%). The probands exhibited greater psychological distress (higher IES and DT scores), and cancer-affected relatives had higher distress levels than healthy relatives (p = 0.008). While no severe psychological distress or PTSD was found, distress was more associated with cancer diagnosis than genetic status. Genetic comprehension was significantly higher in relatives (p = 0.007) and in those who underwent TGC compared to MCG (p < 0.001). TGC carriers also better understood genetic risks and management strategies (p < 0.001). Conclusions Psychological distress and genetic comprehension significantly influenced the communication. TGC enhances understanding more effectively than MCG, highlighting the need for tailored support for both carriers and healthcare professionals to improve cascade counseling and testing rates, and cancer prevention. As we look into the future, we need to critically approach MCG, and determine how to address carriers understanding and prevention needs and reincorporate a more comprehensive genetic risk assessment into the MCG model.
Music therapy in adult hospices: a national multicentre survey Mariagrazia Baroni, Giorgos Tsiris, Annamaria Marzi, Nicola Barbero, Anna Guido, et al. BMJ Supportive and Palliative Care, 2025 BackgroundIn recent years, there has been an increased demand for non-pharmacological, complementary therapies and psychosocial provisions in hospices, aimed at creating spaces for communication and personalised expression in response to the bio-psycho-socio-existential needs of patients and their caregivers. As a contemporary evidence-based professional practice, music therapy is an integral part of multidisciplinary teams in many palliative care settings internationally. In Italy, however, music therapy is a developing area of practice facing certain challenges around professionalisation, funding and service development. This study seeks to explore the current state of music therapy in Italian hospices.MethodsFrom January 2024 to March 2024, an online survey was disseminated to 213 hospices across Italy. The survey consisted of 10 closed-ended questions. Data was analysed using descriptive statistics.ResultsA 73.7% completion rate was achieved. Music-based interventions are provided in 49.6% of hospices (n=62), and 43.5% of these offer a music therapy service led by a qualified music therapist. Most hospices (n=17) offer music therapy sessions for 3 hours per week. Across all hospices, sessions are primarily individual and take place in patients' rooms. The presence of caregivers varies, and patients are referred to music therapy by different professionals in the team. Information was gathered regarding the use of music therapy during sedation and for bereavement support of caregivers, along with details on assessment tools used.ConclusionThis study offers an initial overview of music therapy in hospices across Italy and highlights critical questions regarding team integration, training standards, evaluation and funding.
Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma Simona Serratì, Roberta Di Fonte, Letizia Porcelli, Simona De Summa, Ivana De Risi, et al. Journal of Experimental and Clinical Cancer Research, 2023 Background Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI. Methods We used pre-therapy plasma samples of 110 MM patients and longitudinal samples of 46 patients. Elisa assay and flow cytometry (FCM) were used to measure sPD-L1 and sPD1 concentrations and the percentage of PD1+ EVs and PD-L1+ EVs, released from tumor and immune cells in patients subsets. Transwell assays were conducted to investigate the impact of EVs of each patient subset on MM cells invasion and interaction between tumor cells and macrophages or dendritic cells. Viability assays were performed to assess EVs effect on MM cells and organoids sensitivity to anti-PD1. FCM was used to investigate immunosuppressive markers in EVs and immune cells. Results The concentrations of sPD1 and sPD-L1 in pre-treatment and longitudinal samples did not correlate with anti-PD1 response, instead only tumor-derived PD1+ EVs decreased in long responders while increased during disease progression in responders. Notably, we observed reduction of T cell derived EVs expressing LAG3+ and PD1+ in long responders and their increase in responders experiencing progression. By investigating the impact of EVs on disease progression, we found that those isolated from non-responders and from patients with progression disease accelerated tumor cells invasiveness and migration towards macrophages, while EVs of long responders reduced the metastatic potential of MM cells and neo-angiogenesis. Additionally, the EVs of non-responders and of progression disease patients subset reduced the sensitivity of MM cells and organoids of responder to anti-PD1 and the recruitment of dendritic cells, while the EVs of progression disease subset skewed macrophages to express higher level of PDL-1. Conclusion Collectively, we suggest that the detection of tumor-derived PD1 + EVs may represent a useful tool for monitoring the response to anti-PD1 and a role for EVs shed by tumor and immune cells in promoting tumor progression and immune dysfunction. Graphical Abstract
A Serious Game for the Assessment of Visuomotor Adaptation Capabilities during Locomotion Tasks Employing an Embodied Avatar in Virtual Reality Vladimiro Suglia, Antonio Brunetti, Guido Pasquini, Mariapia Caputo, Tommaso Maria Marvulli, et al. Sensors, 2023 The study of visuomotor adaptation (VMA) capabilities has been encompassed in various experimental protocols aimed at investigating human motor control strategies and/or cognitive functions. VMA-oriented frameworks can have clinical applications, primarily in the investigation and assessment of neuromotor impairments caused by conditions such as Parkinson’s disease or post-stroke, which affect the lives of tens of thousands of people worldwide. Therefore, they can enhance the understanding of the specific mechanisms of such neuromotor disorders, thus being a potential biomarker for recovery, with the aim of being integrated with conventional rehabilitative programs. Virtual Reality (VR) can be entailed in a framework targeting VMA since it allows the development of visual perturbations in a more customizable and realistic way. Moreover, as has been demonstrated in previous works, a serious game (SG) can further increase engagement thanks to the use of full-body embodied avatars. Most studies implementing VMA frameworks have focused on upper limb tasks and have utilized a cursor as visual feedback for the user. Hence, there is a paucity in the literature about VMA-oriented frameworks targeting locomotion tasks. In this article, the authors present the design, development, and testing of an SG-based framework that addresses VMA in a locomotion activity by controlling a full-body moving avatar in a custom VR environment. This workflow includes a set of metrics to quantitatively assess the participants’ performance. Thirteen healthy children were recruited to evaluate the framework. Several quantitative comparisons and analyses were run to validate the different types of introduced visuomotor perturbations and to evaluate the ability of the proposed metrics to describe the difficulty caused by such perturbations. During the experimental sessions, it emerged that the system is safe, easy to use, and practical in a clinical setting. Despite the limited sample size, which represents the main limitation of the study and can be compensated for with future recruitment, the authors claim the potential of this framework as a useful instrument for quantitatively assessing either motor or cognitive impairments. The proposed feature-based approach gives several objective parameters as additional biomarkers that can integrate the conventional clinical scores. Future studies might investigate the relation between the proposed biomarkers and the clinical scores for specific disorders such as Parkinson’s disease and cerebral palsy.