Vittorina Zagonel’s research while affiliated with Istituto Oncologico Veneto and other places

Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-80299-0.

Background Early palliative care (EPC) is a recommended model for improving the quality of life for patients with advanced cancer and their caregivers. However, limited research has focused on the role of psychological evaluation within EPC. The Veneto Institute of Oncology (IOV), a Comprehensive Cancer Centre, employs an interdisciplinary team to assess patients with advanced-stage disease. This study aims to assess the psychological needs of these patients, investigate any correlations between psychological symptoms (PSs) and factors such as awareness of diagnosis and prognosis, symptoms detected using the Edmonton Symptom Assessment System (ESAS), as well as the patient’s gender, age, social issues, and survival and to clarify the psychologist’s role within the interdisciplinary team. Methods Data were retrieved from a prospectively maintained database. From 1st January 2018 to 31st December 2021, 819 consecutive patients were evaluated during EPC consultations, with 753 participants enrolled in the study. The ESAS was administered to each patient before the consultation. Results More than half of the patients (385, 57.1%) reported at least one PS, with an ESAS score of ≥4. Specifically, 34.9% reported depression, 28.7% reported anxiety, and 43.2% indicated feeling “not well.” Referring oncologists tended to overestimate the presence of PSs compared to patient self-reports (51.8% versus 41.3%). According to the psychologists’ assessment, 29.2% of participants were found to have depression, and 10.8% of participants had anxiety. Additionally, 31 patients (10.8%) with psychological disorders were diagnosed with an adaptation disorder related to a physical condition. The psychology service engaged 47% of patients, while 18.5% declined psychological support. Patients exhibiting other ESAS symptoms with scores of ≥4 had an increased odds ratio for reporting PSs of ≥4. However, multivariable analysis revealed no significant relationship between PSs and awareness of diagnosis and prognosis. Conclusion The systematic use of self-assessment in EPC is essential for understanding patient’s experience, determining whether PSs stem from physical disorders, and prioritizing interventions. Awareness of prognosis does not correlate with increased anxiety and depression in patients. Therefore, EPC is an ideal opportunity to discuss prognosis and facilitate patients’ end-of-life choices early in their care journey.

Background In patients with cancer, lean body mass loss is frequent and associated with worse outcomes, including reduced treatment tolerance and survival. Bioelectrical impedance analysis (BIA) is a popular method for body composition assessment. We evaluated the value of BIA-derived body composition parameters in predicting mortality and, for the first time, dose-limiting toxicity (DLT). Patients and methods We conducted a prospective multicenter (n = 12) observational study in adult patients with solid neoplastic disease and receiving primary systemic treatment. We collected information on BIA-derived parameters: phase angle (PhA) <5th percentile of age and gender-specific normative values; standardized PhA (SPA) <−1.65; Nutrigram® <660 mg/24 h/m and <510 mg/24 h/m for males and females, respectively. The primary outcome and the key secondary were 1-year mortality and DLT (any-type severe toxicity requiring a delay in systemic treatment administration or a reduction of its dosage), respectively. Results In total, 640 patients were included. At 12 months, death occurred in 286 patients (47.6%). All BIA-derived body composition parameters were independently associated with death: SPA, hazard ratio (HR) = 1.59 [95% confidence interval (CI) 1.30-1.95] (P < 0.001); PhA, HR = 1.38 (95% CI 1.13-1.69) (P = 0.002); Nutrigram®, HR = 1.71 (95% CI 1.42-2.04) (P < 0.001). DLT occurred in 208 patients (32.5%) and body composition parameters were associated with this outcome, particularly SPA: odds ratio = 6.37 (95% CI 2.33-17.44) (P < 0.001). Conclusions The study confirmed that BIA-derived body composition parameters are independently associated not only with survival but also with DLT. Although our findings were limited to patients receiving first-line systemic treatment, the evidence reported may have important practice implications for the improvement of the clinical work-up of cancer patients.

Background Long‐term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. Methods Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance‐related genes (PD‐L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus–deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. Results In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor‐infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). Conclusions These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Purpose Patients with haematologic malignancies have less access to palliative care and are referred later than patients with solid tumours. We developed a survey to investigate this phenomenon, with the intention of analysing palliative care perceptions among health professionals who treat haematology patients and identifying barriers and facilitators to referrals to palliative care services. Methods This was a multicentre exploratory descriptive web-based survey. A questionnaire was administered to 320 medical and nursing staff members from five Italian haematological units and San Marino’s hospital to investigate their perception of palliative care. Quantitative and qualitative analyses were performed. Results A total of 142/320 healthcare professionals completed the survey, achieving a 44% response rate. Most of the respondents supported the integration of haematology and palliative care and were aware of the role of palliative care. Despite this, only half had an in-hospital palliative care team, and only a few had previously attended a specific training course. The majority agreed with palliative care referral when the prognosis was less than 3 months or when the symptoms were incoercible and with blood transfusions even in the last stages of the disease. Many considered the presence of an in-hospital palliative care team or a case manager, as well as structured palliative care training, as fundamental facilitators of palliative care referrals. Conclusion These results showed that healthcare professionals in haematology generally hold a favourable attitude and a high interest in integrating palliative care into their patients’ care. The low referral rate could depend on clinical, cultural, and organisational issues.

Background Veneto Institute of Oncology has activated a simultaneous care outpatient clinic (SCOC) in which cancer patients with advanced‐stage cancer are evaluated by oncologist and palliative care specialists. This cross‐sectional study investigated patients' perceptions of the quality of this service. Materials and Methods An ad‐hoc self‐administered questionnaire, developed by SCOC team, was used to assess the satisfaction of patients admitted at SCOC consultation. The questionnaire, in addition to the socio‐demographic questions, contains eight questions with the Likert scale: time dedicated, feel listened to, feel understood, feel free to speak openly and to express doubts and concerns, feeling about information and indication received, level of empathy of health care and quality of the relationship, level of professional/quality of performance and utility of consultation, and one open‐ended question. The questionnaire has been proposed to all 174 consecutively admitted patients at SCOC. Results One hundred and sixty‐two patients filled in the questionnaire: 66.7% were male, median age was 71 years, 88.3% had metastatic disease. The time dedicated to SCOC consultation was judged more than adequate (55%) or adequate (35%) by 90% of subjects. Patients completely satisfied about being listened to were 92.5%, with 80.9% being completely satisfied with understanding of their issues and 92% with the freedom to speak and express doubts. Usefulness of the SCOC was rated as excellent by 40% and good by 54.4% of patients. No statistically significant differences were observed in the responses to the questions by gender, age (< or ≥70 years old) and type of tumor. Conclusion Our study shows high levels of satisfactions after SCOC consultation in advanced cancer subjects. Patients' feedback confirmed that SCOC model was effective in helping them during their treatment journey and decision at the end of life. This study encouraged us to enhance our practice of SCOC consultation. Implications for Practice A joint evaluation of patients living with cancer by oncologist and palliative care team (SCOC‐embedded model), has shown to enhance patients' experience/satisfaction with care‐such as listening, understanding, receiving information, symptom control, and decision about future, independently of age, gender, and kind of tumor.