Page 198 - 2019_06-Haematologica-web

F.I. Mulder et al.
continued from previous page
Author (year)
Tafur (2015)69
van Es (2017)70 van Es (2017)71 Vathiotis72
Verso (2012)23 Wang (2017)73 Yust-Katz (2015)74
Zahir (2017)75
VTE: venous thromboembolism; n: number; DLBCL: diffuse large B-cell lymphoma; NR:not reported; NHL: non-Hodgkin lymphoma.
Type
Article
Article Article Article Article Article Article
Study Newly VTE design‡ diagnosed screening
cancer only before study start
Prospective Yes No
Cancer type
Various
Various Pancreatic 7.7
Lung 3.7 Various 3.7 Hepatocellular 11.9 Glioblastoma NR
Median follow up duration in months
10.4
Study Total population* follow up:
patients with VTE, n (%)
241 29 (12.0%)
843 53 (6.3%) 147 20 (13.6%) 130 13 (10.0%) 381 15 (3.9%) 270 16 (5.9%) 440 64 (14.5%)
First 6 months: Patients with VTE, n (%)
24 (10.0%)
53 (6.3%) 13 (8.8%) 7 (5.4%) 15 (3.9%) 11 (4.1%) NR
42 (10.5%)
Prospective Retrospective Retrospective Prospective Retrospective Retrospective
No No
Yes No
Yes No
No No
NR No
Yes No
6.0
Article
Retrospective
No No
Various NR
400 42 (10.5%)
(n=12; 23%), lung (n=6; 11%), urogenital (n=6; 11%), hematologic (n=5; 9%), or central nervous system cancer (n=2; 4%). Almost half of the studies had a prospective design (n=25; 47%); the majority also included incidental- ly detected VTE as outcome event (n=32; 60%). Study group size ranged from 35 to 5,409 patients. Median fol- low-up duration ranged from 2 to 79 months. Key study characteristics of included studies are shown in Table 2.
The 6-month follow-up data were reported in eight of the included studies. For 11 studies, no additional data were obtained after contacting the corresponding author because the authors did not reply despite reminders (n=8), were not able to retrieve the data (n=1), or where not will- ing to share the data (n=2). For 34 studies, additional data were obtained, yielding available 6-month data for 27,849 of the available 34,555 patients (81%).
Risk of bias
Using the pre-specified Quality in Prognosis Studies (QUIPS) criteria, 25 studies were judged to be at high risk of bias for one or more of the bias domains. All eight included abstracts and four articles were judged to be at high risk of bias because of insufficient reporting on meth- ods. Other reasons were a high risk of bias in the applica- bility of the Khorana score (n=1), patient selection (n=4), outcome (n=3), study attrition (n=2), participation (n=4), prognostic factor measurement (n=3), outcome measure- ment (n=5), and confounding factors (n=4). Online Supplementary Table S4 summarizes the risk of bias assess- ment for all studies. A funnel plot did not indicate evi- dence of publication bias (Online Supplementary Figure S1).
Risk classification by the Khorana score
Overall, 6,319 patients (19%) had a Khorana score of 0 points (low risk), 21,172 patients (64%) a score of 1 or 2 points (intermediate risk), and 5,614 patients (17%) a score of 3 or more points (high risk). The group with a Khorana score of 0 or 1 point comprised 15,107 patients (53%), and the group with a score of 2 points or higher 13,148 (47%).
Incidence of venous thromboembolism in the Khorana score risk groups
The incidence of VTE in the first 6-month period was 5.0% (95%CI: 3.9-6.5) in patients with a low-risk Khorana score (0 points), 6.6% (95%CI: 5.6-7.7) in those with an
intermediate-risk Khorana score (1 or 2 points), and 11.0% (95%CI: 8.8-13.8) in those with a high-risk Khorana score (3 points or higher) (Table 3 and Figure 2A-C). The relative risk of VTE in the first six months was 1.8 (95%CI: 1.5- 2.1) for patients with a score of 3 or higher compared to those with a score of 2 or lower (Online Supplementary Figure S2).
In the high-risk Khorana score group, the reported 6- month risk of VTE was lower in studies including patients with lung cancer (6.4%; 95%CI: 4.9-8.4) or hematologic malignancies (7.1%; 95%CI: 2.6-18.4) compared to stud- ies with gastrointestinal (13.0%; 95%CI: 8.5-19.6), uro- genital cancer (18.2%; 95%CI: 8.6-34.6), or various can- cers (11.5%; 95%CI: 8.6-15.3, lung vs. various, P=0.0008; hematologic vs. various, P=0.000). The 6-month incidence in the group with a Khorana score of 1 point or lower was 5.5% (95%CI: 4.5-6.9) compared to 8.9% (95%CI: 7.3- 10.8) in the group with a score of 2 or more points, corre- sponding to a relative risk of 1.5 (95%CI: 1.3-1.8).
During the overall study follow-up period, that ranged from a median of two to 79 months, the summary inci- dence of VTE was 5.7% (95%CI: 4.2-7.9) in patients with a low-risk Khorana score (0 points), 8.6% (95%CI: 7.3- 10.2) in those with an intermediate-risk Khorana score (1 or 2 points), and 14.0% (95%CI:11.7-16.7) in those with a high-risk Khorana score (3 points or higher) (Table 3 and Online Supplementary Figure S3A-C).
Distribution of venous thromboembolic events over the Khorana score risk groups
Of all patients who developed VTE in the first six months, 23.4% (95%CI: 18.4-29.4) had been classified as high risk with the Khorana score (3 points or higher). All other thromboembolic events occurred in the intermedi- ate- or low-risk groups (76.6%; 95%CI:70.6 -81.6). For the total follow-up duration, the proportion of events occur- ring in the high-risk group was 23.7% (95%CI: 18.7-29.5).
Sensitivity analyses
Results were consistent in the sensitivity analysis in which studies judged to be at high risk of bias in one or more of the bias domains were excluded (Table 3). When excluding these studies, the 6-month risks of VTE in patients with a Khorana score of 0, 1 to 2, and 3 points or higher were 4.6% (95%CI: 3.2-6.5), 6.1% ((95%CI: 5.0- 7.4), and 11.1% (95%CI: 8.3-14.7), respectively. The inci-
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