The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis:a systematic review and meta-analysis

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3–6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5–22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3–2.1) in year 2–3, and 2.2 events (95% CI 0.0–4.4) in year 3–5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6–39.6%) at 1 year; 31.1% (95% CI 16.5–43.8%) at 2 years; 31.9% (95% CI 16.8–45.0%) at 3 years; and 35.0% (95% CI 16.8–47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.</p

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis:a systematic review and meta-analysis

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3–6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5–22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3–2.1) in year 2–3, and 2.2 events (95% CI 0.0–4.4) in year 3–5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6–39.6%) at 1 year; 31.1% (95% CI 16.5–43.8%) at 2 years; 31.9% (95% CI 16.8–45.0%) at 3 years; and 35.0% (95% CI 16.8–47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.</p

Quality of cancer treatment care before and after a palliative care pathway:bereaved relatives' perspectives

Objective Appropriate communication between healthcare providers and patients and their families is an essential part of good (palliative) care. We investigated whether implementation of a standardised palliative care pathway (PCP) facilitated communication, that is, aspects of shared decision-making (SDM), including advance care planning (ACP) conversations and satisfaction with care as experienced by bereaved relatives of patients with advanced cancer.Methods We conducted a prospective preintervention and postintervention study in a hospital. Questionnaires were sent to relatives of patients who died between February 2014 and February 2015 (pre-PCP period) or between November 2015 and November 2016 (post-PCP period). Relatives’ perceptions on communication and satisfaction with care were assessed using parts of the Views of Informal Carers—Evaluation of Services and IN-PATSAT32 Questionnaires.Results 195 (46%) and 180 (42%) bereaved relatives completed the questionnaire in the pre-PCP and post-PCP period, respectively. The majority of all patients in both the pre-PCP period and the post-PCP period had been told they had an incurable illness (92% and 89%, respectively, p=0.544), mostly in the presence of a relative (88% and 85%, respectively, p=0.865) and had discussed their preferences for end-of-life (EOL) treatment (82% and 76%, respectively, p=0.426). Bereaved relatives were reasonably satisfied with the received hospital care in both groups.Conclusions We found no overall effect of the PCP on the communication process and satisfaction with EOL care of bereaved relatives. Before the use of the PCP bereaved relatives already reported favourably about the EOL care provided

Abstract P3-15-01: Primary G-CSF Prophylaxis during the First Two Cycles Only or Throughout All Chemotherapy Cycles in Breast Cancer Patients at Risk of Febrile Neutropenia: Final Results from a Phase III Trial of the Dutch Breast Cancer Trialists Group (BOOG)

Abstract Background: In patients at risk of febrile neutropenia (FN), the highest incidence of FN is seen during the first chemotherapy cycles. This observation questions the effectiveness of continued G-CSF prophylaxis during later chemotherapy cycles. Methods: We conducted a multicenter phase III study in breast cancer. Patients were randomized to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). Patients were eligible if treated with 3-weekly chemotherapy, being at risk of FN according to criteria of international guidelines. This was an equivalence study, aimed to include 230 patients, with FN as primary endpoint. Results: An independent Data Safety Monitoring Board recommended premature closure of the study because of an unacceptable increase in FN rate in the experimental arm. In total, 85 patients enrolled the experimental arm and 84 patients the standard arm till 15 th December 2009. Baseline characteristics were well belanced: age ≥65years in 93% versus 95%, ECOG PS of zero in 82% versus 88%, treated with docetaxel containing chemotherapy in (neo)-adjuvant setting in 97% versus 100%, respectively. At least one episode of FN was seen in 27 (32%) patients of the experimental arm compared with 4 (5%) patients in the standard arm (P&amp;lt;0.0001). Notably, in the experimental arm FN occurred predominantly in the third cycle, whereas in the standard arm FN was seen throughout all cycles. Fever, infection and/or mucositis led to serious adverse events in 31 (36%) patients in the experimental arm versus in 11 (13%) patients in the standard arm (P&amp;lt;0.001). In both arms, 5% of patients stopped or changed treatment because of toxicity. Most patients experienced only one FN episode. In these, chemotherapy was mostly given as planned, but in 61 % of patients with secondary G-CSF prophylaxis and in 21% of patients with secondary antibiotic prophylaxis (in the experimental arm). Conclusion: We conclude that in patients at risk of FN, primary G-CSF prophylaxis cannot be limited to the first chemotherapy cycles, despite the well known increased FN incidence in the first cycles without prophylaxis. With only 2 cycles protected, FN risk is increased in the third cycle. Support: The Netherlands organization for health research and development (ZonMw) and sanofi-aventis Netherlands B.V. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-01.</jats:p