Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Implementation of a systematic comprehensive geriatric assessment for elderly patients suspected of pulmonary hypertension.

BACKGROUND: The phenotype of patients seen for a suspicion of pulmonary hypertension has changed, with an increasing age and frequency of comorbidities. Selection of elderly patients, in whom a classical work-up is mandatory, is challenging. Comprehensive geriatric assessment (CGA) has modified the management of elderly patients with cancer. Pulmonary hypertension (PH) shares with cancer a functional impact and may evolve rapidly, depending on the group of PH. We assessed the impact of a systematic CGA in patients over 70 years old referred for a suspicion of PH. METHODS: A standardised CGA was performed on every patient older than 70 years old, referred for a PH suspicion, before considering invasive tests for diagnosis and treatment, between July 2014 and May 2019. Our primary aim was to describe the impact of CGA on the decision to stop or pursue the recommended diagnostic work-up for PH. RESULTS: Among the thirty-one patients evaluated [mean age 81,5 (72-91) years], a negative CGA leads to stop the diagnostic work-up in eleven patients. Among the nineteen remaining patients, sixteen had confirmed PH, with half being chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Our study indicates that comprehensive geriatric assessment could be an excellent first screen for elderly patients referred for a PH suspicion. Involving a geriatric physician stopped the investigations in one third of patients. In patients with a favourable CGA, PH was confirmed in most of the cases, with chronic thromboembolic pulmonary hypertension being the first cause of PH.

DLNO/DLCO ratio evolution under targeted therapy in patients with pulmonary hypertension.

The ratio of the diffusing capacity of the lung for carbon monoxide (DLCO) and for nitric oxide (DLNO) measured simultaneously is modified in patients with precapillary pulmonary hypertension (PH). The potential impact of targeted therapy on the DLCO/DLNO ratio is unknown. Simultaneous measurements of DLNO and DLCO were performed at baseline, 3-4 month follow-up (first evaluation) and 12-month follow-up (second evaluation) after initiation of targeted PH therapies in incident cases of precapillary PH. The main outcome was the change in DLNO/DLCO ratio under treatment between baseline and the first evaluation. Twenty-nine patients were included (mean age: 66.8 years, 62.1% female). No significant change in the DLNO/DLCO ratio was found between baseline and the first evaluation. Similarly, no significant differences were noted with regard to changes in Dm or Vc, the DLNO/DLCO ratio in different patient subgroups, or in the 20 patients evaluated at the second follow-up. Within the limitations of this study, the DLNO/DLCO ratio is not useful in monitoring the response to treatment in PH.

Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition which should be screened in patient with persistent dyspnea after pulmonary embolism (PE). After PE, CTEPH incidence was estimated between 0.1 and 9.1% in overall patients. Although cancer is associated with an increased risk of CTEPH, CTEPH incidence is still unknown in cancer patients with PE. We aimed to estimate the frequency CTEPH-likely patients after PE, in cancer patients. MATERIALS: We individualized cancer patients of a monocentric prospective registry including consecutive patients with symptomatic PE. The primary outcome was the frequency of "CTEPH-likely" patients defined by the European Respiratory Society (ERS) guidelines (an accelerated tricuspid regurgitation more than 2.8m/s and at least 1-2 segmental or larger-sized defects, after more than 3 months of therapeutic anticoagulation). RESULTS: We included 129 cancer patients with PE. Colorectal cancer (19%), breast cancer (17%) and prostate cancer (15%) were the most frequent cancers. PE occurred after surgery or medical immobilization in 17% of patients, while 26% of patients had history of venous thromboembolism. During the follow-up, 2 patients (1.5%) had a clinical suspicion of CTEPH and only 1 patient with ovarian cancer (0.75% 95%CI [0.0%-2.2%]) was classified as "CTEPH-likely", 6 months after PE. CONCLUSION: The frequency of screening for CTEPH seems negligible in PE patients with cancer. Concomitant cancer may affect the clinical suspicion of CTEPH.

Assessment of a flow cytometry technique for studying signaling pathways in platelets: Monitoring of VASP phosphorylation in clinical samples.

A recently released kit (PerFix EXPOSE) was reported to improve the measurement of the degree of phosphorylation of proteins in leukocytes by flow cytometry. We tested its adaptation for platelets to monitor vasodilator-stimulated phosphoprotein (VASP) phosphorylation, which is the basis of a currently used test for the assessment of the pharmacological response to P2Y12 antagonists (PLT VASP/P2Y12). The PerFix EXPOSE kit was compared to the PLT VASP/P2Y12 kit by using blood samples drawn at 24 h post clopidogrel dose from 19 patients hospitalized for a non-cardio-embolic ischemic stroke and treated with clopidogrel monotherapy for at least five days in an observational study. The platelet PerFix method was based on adaptation of the volume of the sample, the centrifugation speed and the incubation temperature. Poor agreement between prevention by adenosine diphosphate (ADP) of PGE1-induced cAMP-mediated VASP phosphorylation and ADP induced aggregation assessed by Light Transmittance Aggregometry was found. We found a significant correlation between the PLT VASP/P2Y12 kit and the PerFix EXPOSE kit. The PerFix EXPOSE kit may also be helpful to monitor adverse effects of second-generation tyrosine kinase inhibitors on platelets.