Abstract Background: Obesity and metabolic disorders have been associated with poorer outcomes in many cohorts of breast cancer (BC) patients, with poor evidence from Mediterranean cohorts. The purpose of this study is to investigate the prognostic potential of anthropometric variables in early BC patients living in a Southern region of Italy. Methods: This prospective cohort study enrolled 955 consecutive early BC patients treated at the Istituto Nazionale dei Tumori “G. Pascale” and at the University Hospital “Federico II”, Naples, Italy, between January 2009 and December 2013. Median follow-up was 11.8 years and ended on June 15 th 2022. Anthropometric measurements and indices namely body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), as well as Metabolic Syndrome (MetS) and its components, were collected. All-cause and BC-specific mortality were calculated. Results: Mean age was 55.3 years (±12.5 years); 61% of patients were post-menopausal. At data cut-off, 208 (22%) patients had died, 131 (14%) of whom from BC. Obesity was found in 29% of patients. High WC or WHR and the presence of MetS were associated with a moderately increased risk of all-cause mortality (WC ≥ 88 cm, HR=1.39, 95%CI:1.00-1.94; WHR > 0.85, HR=1.62, 95%CI:1.12-2.37; MetS, HR=1.61, 95%CI:1.12-2.32). An increased BC-specific mortality risk was found in obese patients (HR=1.72, 95%CI:1.06-2.78), in those with WC ≥88 (HR=1.71, 95%CI:1.12-2.61)and in those with high WHR, both when evaluated as a categorical variable (WHR>0.85, HR=1.80, 95%CI:1.13-2.86) and as a continuous variable (for each 0.1-U increase in WHR, HR=1.33, 95%CI:1.08-1.63) as well as the presence of MetS (HR=1.81, 95%CI:1.51-2.85). These associations varied according to menopausal status and BC subtype. Conclusions: Central obesity significantly increased total and BC-specific mortality particularly in pre-menopausal women, while in post-menopause the MetS was a stronger risk factor. These associations were significant mainly in luminal subtypes while no relevant findings were observed in TNBC. The magnitude of risk suggests that obesity and the presence of the MetS or its single components may nullify the benefit of effective BC therapies. Active lifestyle intervention studies should be encouraged for several expected beneficial effects.
Background The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. Methods This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ 2 test for trends relative to the questions with 3 or more options. Results This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. Conclusion Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.
Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.
e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values < 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.
Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n = 43) or NabGem (n = 117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28 weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86 weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p < 0.0001). In the FFN → NabGem and NabGem → FFN groups, median overall survival was 51.2 and 71.6 weeks (HR: 0.69; p = 0.15). In patients receiving NabGem, second-line FFN, compared with FOLFOX/CAPOX or FOLFIRI, improved median progression-free survival 2 (25.6 vs 12.1 weeks; HR: 0.47; p = 0.0067) and median overall survival 2 (39.0 vs 19.14 weeks; HR: 0.49; p = 0.032). Conclusion: First-line FFN and NabGem promote similar clinical outcomes. Second-line FFN should be considered after NabGem.
Abstract Purpose Obesity and insulin resistance have been associated with poor prognosis in breast cancer (BC). The present prospective study aimed to investigate the impact of metabolic syndrome (MetS) and its components on early BC (eBC) patients’ outcome. Methods MetS was defined by the presence of 3 to 5 of the following components: waist circumference > 88 cm, blood pressure ≥ 130/≥ 85 mmHg, serum levels of triglycerides ≥ 150 mg/dL, high density lipoprotein < 50 mg/dL and fasting glucose ≥ 110 mg/dL. Seven hundred and seventeen patients with data on ≥ 4 MetS components at BC diagnosis were enrolled. Study population was divided into two groups: patients with < 3 (non-MetS) vs. ≥ 3 components (MetS). Categorical variables were analyzed by Chi-square test and survival data by log-rank test and Cox proportional hazards regression model . Results Overall, 544 (75.9%) and 173 (24.1%) women were categorized as non-MetS and MetS, respectively. MetS patients were more likely to be older, postmenopausal, and insulin-resistant compared to non-MetS patients ( p < 0.05). In multivariate analysis, MetS patients had a numerically higher risk of relapse [disease-free survival (DFS), hazard ratio (HR) 1.51, p = 0.07] and a significantly higher risk of death compared to non-MetS patients [overall survival (OS), HR 3.01, p < 0.0001; breast cancer-specific survival (BCSS), HR 3.16, p = 0.001]. Additionally, patients with 1 to 2 components of MetS had an increased risk of dying compared to patients with 0 components (OS, HR 4.90, p = 0.01; BCSS, HR 6.07, p = 0.02). Conclusions MetS correlated with poor outcome in eBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival.
Abstract Introduction: Mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) are the rarest neuroendocrine appendiceal neoplasms, for which no standard treatment guidelines are available. Here, we present a case report of a pelvic MiNEN. Case description: A 41-year-old woman underwent clinical evaluation to determine the causes of her infertility. Medical tests revealed a massive cystic mass in the left pelvis and a small fluid-filled nodule originating from the appendix. Fertility-sparing surgery evidenced an appendiceal MiNEN, with a low-grade neuroendocrine component in the context of a low-grade mucinous neoplasm (LAMN). Pathological stage was pT4 N0 M1 (according to the AJCC VIII ed.), as the tumour reached the visceral peritoneum, showing no metastatic lymph node involvement. A single metastatic nodule expressing neuroendocrine features was found in the omentum. Instrumental re-evaluation performed after surgery revealed two additional abdominal spots, suspicious for metastases. After multidisciplinary discussion, a second surgery was performed, followed by intraperitoneal intraoperative hyperthermia (HIPEC). Three months later, CT scan revealed a neoformation between the stomach and the pancreas tail, suspicious for disease progression. Surgical biopsy was deemed unfeasible. Since LAMN was the main component of the pelvic mass previously removed, the patient underwent oral fluoropyrimidine-based chemotherapy. Simultaneously, patient was treated with somatostatin analogues (SAs), after assessing a moderate 68Ga-PET scan positivity. The patient is currently on treatment, alive and progression-free after 28 months. Conclusion: Our case highlights the importance of multidisciplinary approach and literature review to guarantee the most appropriate management of rare diseases such MiNENs, underlining the unmet need of common guidelines.
Thymic epithelial tumors (TETs) are rare malignancies with heterogeneous clinical manifestations. The high frequency of autoimmune paraneoplastic disorders observed in such patients requires caution when using COVID-19 vaccines. Furthermore, TETs are often associated with severe immunodeficiency, making it difficult to predict vaccine immunization. Therefore, we aimed to evaluate immune response to COVID-19 vaccine in patients with TETs.We conducted a prospective study enrolling patients who underwent the SARS-Cov-2 mRNA full vaccine cycle (two doses plus a booster after 6 months of BNT162b2). All patients were enrolled before receiving 1st vaccine dose and were followed over the vaccination cycle for up to 6 months after the booster dose to i) assess humoral and cellular responses, ii) define biomarkers predictive of effective immunization, and iii) evaluate the safety of the vaccine.At the end of the full vaccine cycle, 27 (61.4%) patients developed humoral and 38 (86.4%) cellular responses (IFN γ release by stimulated cells) and showed an increase in activated TH1 and TH17 cells, particularly significant after the booster dose. The number of B and T lymphocytes at baseline was predictive of humoral and cellular responses, respectively. Patients with no evidence of tumor lesions had a higher probability of achieving a humoral response than those with evidence of the disease. Furthermore, the percentage of patients with immune-related disorders (75%), particularly Good's syndrome (47.7%) and myasthenia gravis (29.5%), did not change over the entire vaccine cycle. Overall, 19 of the 44 enrolled patients (43.2%) had COVID-19 during the observation period; none required hospitalization or oxygen support, and no fatalities were observed.SARS-Cov-2 mRNA vaccine determines the immune responses in patients with TET, particularly after the booster dose, and in patients with no evidence of tumor lesions. Preliminary analysis of B and T lymphocytes may help identify patients who have a lower probability of achieving effective humoral and cellular responses and thus may need passive immunization. The vaccine prevented severe COVID-19 infection and is safe.
