Page 11 - JCTR-11-4

Journal of Clinical and
Translational Research Hidden cancer after VTE

period); (ii) study population characteristics (sample size, Corp, United States of America) and R, version 4.3.2
age, gender); (iii) screening strategy; (iv) follow-up period (R Foundation for Statistical Computing, Austria;
after the episode of VTE; (v) occult-cancer detection; www.r‐project.org).
(vi) cancer-related mortality; and (vii) overall mortality.
3. Results
2.4. Outcomes
3.1. Search results
The primary outcome was cancer-related mortality.
Secondary outcomes were the incidence of previously Initially, 889 studies were identified, from which 461
undiagnosed solid or hematological cancer at initial remained after removing duplicates. Following a full-
screening or during follow-up and overall mortality. Cancer text review to assess eligibility, 10 studies were included
16-19
was confirmed by histology or cytology or unequivocally in the meta-analysis. These comprised four RCTs.
20-25
diagnosed by imaging. and six prospective studies. (Figure 1). The definition
of unprovoked VTE was consistent across the studies. It
2.5. Assessment of risk of bias in the studies primarily included symptomatic PE or DVT that could not
We assessed the risk of bias in randomized controlled trials be attributed to known risk factors, such as recent surgery,
(RCTs) using the Jadad scale. This scale, also known as lower extremity trauma, recent immobilization, known
14
the Oxford quality scoring system, focuses on evaluating thrombophilia, pregnancy, or the puerperium.
the descriptions of randomization (up to two points), A total of 2621 patients were enrolled, with 1644
double-blinding (up to two points), and withdrawals participating in RCTs and 977 in observational prospective
and dropouts (up to one point). Studies are scored on a studies. Among these, 1506 patients underwent extensive
scale from zero to five, with higher scores indicating screening, while 1115 received limited screening. The
better quality. A score of three or above is the reference comprehensive screening protocols comprised CT, 16-18,21-23
20
point for adequate trial quality. The Newcastle–Ottawa abdominal ultrasonography, or whole-body positron
scale (NOS) was used for prospective studies. The NOS emission tomography-CT (PET/CT). 19,24,25 Furthermore,
15
contains eight items, categorized into three dimensions, two studies included gastrointestinal endoscopic
including selection, comparability, and—depending on examinations. 16,21 The limited screening approaches
the study type—outcome (cohort studies) or exposure involved the collection of medical histories, physical
(case-control studies). For each item, a series of response examination, basic blood tests, chest radiography, and
options is provided. A star system is used to assess study age- and gender-specific cancer screenings (including
quality, such that the highest quality studies are awarded those for breast, cervical, and prostate cancers).
a maximum of one star for each item, except for the item
related to comparability, which allows the assignment of 3.2. Randomized controlled trials related to cancer
two stars. Therefore, the NOS ranges from zero to nine investigations for patients with unprovoked VTE
stars. The risk of bias is low, with ≥7 stars. Judgments were Four RCTs, enrolling 1644 participants, fulfilled the
made with consensus among four reviewers (A.F.M., J.M., eligibility criteria for inclusion in this review. 16-19 Three
C.L.A.A., and A.M.C.M.). Disagreements were resolved by studies assessed the effect of extensive tests, including CT
consensus. scanning, versus tests at the physician’s discretion, 16-18 while
one study evaluated PET/CT scanning versus standard
2.6. Statistical analysis testing (Table 1).
19
This review aimed to compare the performance of the The SOMIT study was this field’s first major randomized
limited and extensive cancer screening strategies for occult study. In the study, 99 participants were randomized to
16
cancer detection in patients presenting with idiopathic the extensive screening group, and 102 were randomized
VTE. to the control group. Of these, 50.2% were female, and the
For each study, we retrieved data, and a weighted mean age was 66.4 ± 13.1 years. The exhaustive screening
pooled analysis was performed. The diagnostic OR, an strategy evaluated in the SOMIT trial included ultrasound
overall performance measure, was calculated and pooled and CT-scan of the abdomen and pelvis, upper and lower
to create a global estimate for each strategy. This estimate gastrointestinal endoscopies, sputum cytology, tumor
displays the probability that VTE patients who underwent markers, mammography, Papanicolaou smear in women,
the extensive screening had occult cancer, compared with and prostate-specific antigen (PSA) and transabdominal
those who underwent a limited screening. We expressed prostate ultrasound in men. Patients in the control group
data with their 95% CI intervals. Statistical analyses were were investigated at the physician’s discretion. All tests
performed using SPSS software, version 29.0 (SPSS, IBM were completed within 4 weeks of the VTE diagnosis. The

Volume 11 Issue 4 (2025) 5 doi: 10.36922/jctr.24.00069