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Risk of Venous Thromboembolism and Major Bleeding in the Clinical Course of Osteosarcoma and Ewing Sarcoma Patients

M.A.M. Stals1, F.HJ Kaptein1, R.E Evenhuis2, AJ Gelderblom3, M.V Huisman1, DSA Karis2, RWD Noten1, SC Cannegieter1,4, HH Versteeg1, MAJ van de Sande2, FA Klok1

1Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands, 2Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, Netherlands, 3Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands, 4Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands

Abstract Number: PB1095

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Cancer Associated Thrombosis

Background: Patients with osteosarcoma and Ewing sarcoma are considered to have a high risk of venous thromboembolism (VTE), although the exact incidence is understudied.

Aims: To study the incidence of VTE and major bleeding (MB) in these patients.  

Methods: We performed a chart review in patients treated for osteosarcoma (OS) or Ewing sarcoma (ES) in our hospital between 1980 and 2018. The study was approved by the Institutional Review Board. Patient charts were scrutinized for patient and tumor characteristics, and outcome events, the latter adjudicated by an independent expert. Cumulative incidences were estimated using Kaplan-Meier and cumulative incidence competing risk (CICR) method. Multivariable time-dependent Cox models were used to determine the association between outcome events and mortality.

Results: Baseline characteristics of 520 osteosarcoma and 165 Ewing sarcoma patients are shown in Table 1. VTE occurred in 65 OS patients (13%) and 11 ES patients (6.7%), MB in 31 OS patients (6.0%) and 9 ES patients (5.5%). Adjusted cumulative incidences for VTE and MB at 3, 6, 9, 12 and 24 months are presented in Table 2. The most frequent VTE presentation was arm vein thrombosis (32% and 45% in OS and ES, respectively), mostly related to central venous catheters (CVC; in 18/21 OS patients and 5/5 ES patients). From the 31 MB complications in osteosarcoma patients, 13 patients were known to use prophylactic or therapeutic anticoagulants (42%). The majority of MBs (84% in OS, 78% in ES) were bleedings within metastases or rebleeds after surgery. In osteosarcoma, VTE and MB were both associated with all-cause mortality (adjusted HRs 1.9 (95%CI 1.3-2.7) and 3.3 (95%CI 2.1-5.1) respectively), whereas this association was only present for MB in Ewing sarcoma (adjusted HR 2.9 (95%CI 1.0-8.1)).

Table 1. Baseline characteristics of osteosarcoma and Ewing sarcoma patients
Baseline characteristics Osteosarcoma Ewing sarcoma
Number of patients 520 165
Age at diagnosis – years
        Mean (+/- SD)
        Range
32 (19)
3.5-84
23 (13)
1.2-67
Gender – no (%)
        Male
        Female
288 (55)
232 (45)
113 (69)
52 (32)
Presence of distant metastases at time of diagnosis – no (%) 107 (21) 50 (30)
Tumor grade – no (%)
        High grade sarcoma
        Low grade sarcoma
        Intermediate grade
        Undefined
453 (87)
40 (7.7)
10 (1.9)
17 (3.3)
NA
NA
NA
NA
Presence of CVC – no (%)
        Yes
        No
        Unknown
394 (76)
91 (18)
35 (6.7)
152 (92)
3 (2)
10 (6.1)
Patients died – no (%) 257 (49) 88 (53)
Median follow-up time in months – IQR 60 (22-142) 42 (19-124)
Note: SD: standard deviation; no: number; CVC: central venous catheter; IQR: interquartile range; NA: not available

Baseline characteristics of osteosarcoma patients and Ewing sarcoma patients   

Table 2. Adjusted cumulative incidences of venous thrombotic complications and major bleeding events in osteosarcoma patients and Ewing sarcoma patients
Index date: date of histological diagnosis of OS or E​​​​S
Osteosarcoma
VTE
% (95% CI)
Ewing sarcoma
VTE
% (95% CI)
Osteosarcoma
MB
% (95% CI)
Ewing sarcoma
MB
% (95% CI)
3 months
5.2 (3.5-7.3)
1.8 (0.50-4.8)
1.2 (0.48-2.4)
0
6 months
6.7 (4.8-9.1)
1.8 (0.50-4.8)
2.3 (1.3-3.9)
0.61 (0.06-3.1)
9 months
7.5 (5.4-10)
4.2 (1.9-8.1
2.5 (1.4-4.1)
0.61 (0.06-3.1)
12 months
8.3 (6.1-11)
6.1 (3.1-10)
3.3 (2.0-5.1)
1.2 (0.24-4.0)
24 months
8.8 (6.6-11)
6.7 (3.5-11)
4.0 (2.6-6.0)
2.5 (0.81-5.8)​​​​
Note: OS: osteosarcoma; ES: Ewing sarcoma; VTE: venous thromboembolism; MB: major bleeding; CI: confidence interval
Adjusted cumulative incidence: cumulative incidence adjusted for competing risk of death (following the CICR method)  

Adjusted cumulative incidences of venous thrombotic complications and major bleeding events in osteosarcoma patients and Ewing sarcoma patients

Conclusions: Our findings provide accurate estimations of the incidence and prognostic relevance of VTE and MB in patients with osteosarcoma and Ewing sarcoma.

To cite this abstract in AMA style:

Stals MAM, HJ Kaptein F, E Evenhuis R, AJ Gelderblom , V Huisman M, DSA Karis , RWD Noten , SC Cannegieter , HH Versteeg , MAJ van de Sande , FA Klok . Risk of Venous Thromboembolism and Major Bleeding in the Clinical Course of Osteosarcoma and Ewing Sarcoma Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/risk-of-venous-thromboembolism-and-major-bleeding-in-the-clinical-course-of-osteosarcoma-and-ewing-sarcoma-patients/. Accessed May 19, 2022.

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