Assessment of bleeding risk in cancer patients treated with anticoagulants for venous thromboembolic events.

Introduction: Anticoagulant is the cornerstone of the management of VTE at the cost of a non-negligible risk of bleeding. Reliable and validated clinical tools to predict thromboembolic and hemorrhagic events are crucial for individualized decision-making for the type and duration of anticoagulant treatment. We evaluate the available risk models in real life cancer patients with VTE. The objectives of the study were to describe the bleeding of cancer patients with VTE and to evaluate the performance of the different bleeding models to predict the risk of bleeding during a 6-month follow-up. Materials and Methods: VTE-diagnosed patient's demographic and clinical characteristics, treatment regimens and outcomes for up to 6 months were collected. The primary endpoint was the occurrence of a major bleeding (MB) or a clinically relevant non major bleeding (CRNMB) event, categorized according to the ISTH criteria. Results: During the 6-months follow-up period, 26 out of 110 included patients (26.7%) experienced a bleeding event, with 3 recurrences of bleeding. Out of the 29 bleeding events, 19 events were CRNMB and 10 MB. One patient died because of a MB. Bleeding occurred in 27 % of the patients treated with DOACs and 22% of the patients treated with LMWH. Most of the bleedings were gastrointestinal (9 events, 31%); 26.9% of the bleedings occurred in patient with colorectal cancer and 19.6% in patients with lung cancer. In our cohort, none of the 10 RAMs used in our study were able to distinguish cancer patients with a low risk of bleeding, from all bleeding or non-bleeding patients. The Nieto et al. RAM had the best overall performance (C-statistic = 0.730, 95% CI (0.619-0.840)). However, it classified 1 out of 5 patients with major bleeding in the low risk of bleeding group. The rest of the RAMs showed a suboptimal result, with a range of C-statistic between 0.489, 95%CI (0.360-0.617)) and 0.532, 95%CI (0.406-0.658)). Conclusions: The management of CAT patients is challenging due to a higher risk of both recurrent VTE and bleeding events, as compared with non-cancer patients with VTE. None of the existing RAMs was able to consistently identify patients with risk of anticoagulant associated bleeding events.

Cancer-Associated Thrombosis on Bevacizumab: Risk of Recurrence and Bleeding When Bevacizumab Is Stopped or Continued.

Cancer-associated thrombosis (CAT) is a common complication during cancer, with complex management due to an increased risk of both recurrence and bleeding. Bevacizumab is an effective anti-angiogenic treatment but increases the risk of bleeding and potentially the risk of venous thromboembolism (VTE). The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab, according to the continuation or discontinuation of bevacizumab. In a retrospective multicenter study, patients receiving anticoagulant for CAT occurring under bevacizumab therapy were included. The primary endpoint combined recurrent VTE and/or major or clinically relevant non-major bleeding. Among the 162 patients included, bevacizumab was discontinued in 70 (43.2%) patients and continued in 92 (56.8%) patients. After a median follow-up of 318 days, 21 (30.0%) patients in the discontinuation group experienced VTE recurrence or major or clinically relevant non-major bleeding, compared to 27 (29.3%) in the continuation group. The analysis of survival following the first event showed no significant difference between the groups in uni- or multivariate analysis (p = 0.19). The primary endpoint was not influenced by the duration of bevacizumab exposure. These results suggest that the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab is not modified regardless of whether bevacizumab is continued or discontinued.

Diagnostic Approach for Venous Thromboembolism in Cancer Patients.

Venous thromboembolic disease (VTE) is a common complication in cancer patients. The currently recommended VTE diagnostic approach involves a step-by-step algorithm, which is based on the assessment of clinical probability, D-dimer measurement, and/or diagnostic imaging. While this diagnostic strategy is well validated and efficient in the noncancer population, its use in cancer patients is less satisfactory. Cancer patients often present nonspecific VTE symptoms resulting in less discriminatory power of the proposed clinical prediction rules. Furthermore, D-dimer levels are often increased because of a hypercoagulable state associated with the tumor process. Consequently, the vast majority of patients require imaging tests. In order to improve VTE exclusion in cancer patients, several approaches have been developed. The first approach consists of ordering imaging tests to all patients, despite overexposing a population known to have mostly multiple comorbidities to radiations and contrast products. The second approach consists of new diagnostic algorithms based on clinical probability assessment with different D-dimer thresholds, e.g., the YEARS algorithm, which shows promise in improving the diagnosis of PE in cancer patients. The third approach uses an adjusted D-dimer threshold, to age, pretest probability, clinical criteria, or other criteria. These different diagnostic strategies have not been compared head-to-head. In conclusion, despite having several proposed diagnostic approaches to diagnose VTE in cancer patients, we still lack a dedicated diagnostic algorithm specific for this population.

Granulosa tumor: two spontaneous pregnancies after combined medico-surgical treatment: case report and review of the literature.

BACKGROUND: Granulosa tumor is a rare tumor that arises from the mesenchyme and the sexual cord of the ovary. The prognosis is generally excellent, and treatment is mainly based on surgery, followed by chemotherapy depending on the extension of the disease. However, "the obstetrical prognosis" is compromised. CASE PRESENTATION: We report the case of a 32-year-old Caucasian patient who was diagnosed during a primary infertility assessment with an ultrasound image of a 39 mm organic left ovarian cyst confirmed on pelvic magnetic resonance imaging with infiltration of the uterosacral space. Tumor markers, including cancer antigen 125, alpha fetoprotein, and ß-human chorionic gonadotropin, were normal. Histological study of biopsies of the ovarian lesion taken during exploratory laparoscopy confirmed the diagnosis of adult granulosa tumor. After a normal extension assessment including a thoracoabdominopelvic computed tomography scan and a positron emission tomography scan, the patient underwent complete conservative surgery and the disease was classified as stage Ic. Three cycles of adjuvant chemotherapy according to the "BEP" protocol combining bleomycin, etoposide, and cisplatin were performed after oocyte cryopreservation. After a 5-year follow-up period, the patient had no sign of tumor progression and had two spontaneous pregnancies, the first occurring 3 months after the end of chemotherapy and the second 14 months later. CONCLUSION: Granulosa cell tumor remains a rare tumor whose management considerably compromises fertility and reduces the chances of having a spontaneous pregnancy. The particularity of our observation is that the diagnosis of the granulosa tumor was made following a primary infertility assessment and that the patient had two spontaneous pregnancies 3 months after the end of a medico-surgical treatment known to be very gonadotoxic.

In Search of the Appropriate Anticoagulant-Associated Bleeding Risk Assessment Model for Cancer-Associated Thrombosis Patients.

Patients with venous thromboembolism events (VTE) in the context of cancer should receive anticoagulants as long as the cancer is active. Therefore, a tailor-made anticoagulation strategy should rely on an individualized risk assessment model (RAM) of recurrent VTE and anticoagulant-associated bleeding. The aim of this review is to investigate the applicability of the currently available RAMs for anticoagulant-associated bleeding after VTE in the CAT population and to provide new insights on how we can succeed in developing a new anticoagulant-associated bleeding RAM for the current medical care of CAT patients. A systematic search for peer-reviewed publications was performed in PubMed. Studies, including systematic reviews, were eligible if they comprised patients with VTE and used a design for developing a prediction model, score, or other prognostic tools for anticoagulant-associated bleeding during anticoagulant treatment. Out of 15 RAMs, just the CAT-BLEED was developed for CAT patients and none of the presented RAMs developed for the VTE general population were externally validated in a population of CAT patients. The current review illustrates the limitations of the available RAMs for anticoagulant-associated bleeding in CAT patients. The development of a RAM for bleeding risk assessment in patients with CAT is warranted.