Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, setting, and participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main outcomes and measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and relevance: This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis

Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes

Simple Summary Despite the approval of new targeted therapies for pancreatic neuroendocrine tumors (PanNETs) over the past decades, the early identification of resistant tumors remains the major challenge, mainly because clear signs of tumor shrinkage are rarely achieved by imaging assessment. Starting from the hypothesis that angiogenesis can be implicated in the resistance to mTOR inhibitors, we evaluated a specific angiogenesis panel (through the measurement of soluble biomarkers for angiogenesis turnover, circulating endothelial cells, and circulating progenitors) as possible predictors of resistance to everolimus or everolimus efficacy in PanNETs. Our study showed that none of the investigated categories of biomarkers had a predictive value for everolimus resistance or efficacy. However, we suggest that circulating endothelial progenitors might be surrogate biomarkers for angiogenesis activity in PanNETs during everolimus treatment, and their baseline levels might correlate with survival outcomes. These data have never been reported before for NETs. Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE)

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients’ care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population