Cancer associated incidental pulmonary embolism: Clinical characteristics and survival outcomes Sai-Ching Jim Yeung, MD, PhD, Aiham Qdaisat, MD, Mona Kamal, MD, PhD, Aisha Al-Breiki, MD,Biman Goswami, MD, Carol C. Wu, MD, Shouhao Zhou, PhD, Terry Rice, MD, Kumar Alagappan, MD The University of Texas MD Anderson Cancer Center, Houston, Tx, USA

Cancer associated incidental pulmonary embolism: Clinical characteristics and survival outcomes Sai-Ching Jim Yeung, MD, PhD, Aiham Qdaisat, MD, Mona Kamal, MD, PhD, Aisha Al-Breiki, MD,Biman Goswami, MD, Carol C. Wu, MD, Shouhao Zhou, PhD, Terry Rice, MD, Kumar Alagappan, MD The University of Texas MD Anderson Cancer Center, Houston, Tx, USA

IntroductionMalignancy is considered one of the main risk factors for venous thromboembolism (VTE).1 In cancer patients, incidental VTEs including incidental pulmonary embolisms (IPE) are common.2,3 These events are usually found during routine staging or follow up imaging studies in asymptomatic patients.2-4 With the introduction of high resolution CT scanners, the incidence of IPE rose dramatically.5 Despite being an incidental finding, IPE carry high risk of morbidity and mortality. Determining the clinical characteristics and the outcome of patients with IPE is important and can further improve the management plan for the patient.

References1. Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003;107(23 Suppl 1):I17-21.2. Gladish GW, Choe DH, Marom EM, Sabloff BS, Broemeling LD, Munden RF. Incidental pulmonary emboli in oncology patients: prevalence, CT evaluation, and natural history. Radiology. 2006;240(1):246-255.3. Di Nisio M, Ferrante N, De Tursi M, et al. Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost. 2010;104(5):1049-1054.4. Abdel-Razeq HN, Mansour AH, Ismael YM. Incidental pulmonary embolism in cancer patients: clinical characteristics and outcome--a comprehensive cancer center experience. Vasc Health Risk Manag. 2011;7:153-158.5. Tresoldi S, Flor N, Luciani A, Lombardi MA, Colombo B, Cornalba G. Contrast enhanced chest-MDCT in oncologic patients. Prospective evaluation of the prevalence of incidental pulmonary embolism and added value of thin reconstructions. Eur Radiol. 2015;25(11):3200-3206.

ConclusionsPulmonary embolisms that are found incidentally in cancer patients during routine staging or follow up imaging studies share similar clinical characteristics with symptomatic ones, and once they occur, they poorly affect the patients’ outcomes. Concurrent incidental venous thromboembolisms are common and when they occur, they lead to poorer outcomes. Proper identification and management of these event is crucial.

MethodsTo identify clinical characteristics and examine the outcome of patients with IPE, we conducted a 1:2 ratio case-control study at The University of Texas MD Anderson Cancer Center. All patients with confirmed IPE who visited the emergency department between 01/01/2006 and 01/01/2016, were matched with two controls of cancer patients without IPE on age, gender, race, cancer type, cancer stage, CT scan date, Charlson comorbidity index, renal function, and type of insurance. Student’s t-test, Wilcoxon Mann–Whitney U test or Chi-squared test was used to compare characteristics variables, where appropriate. A Kaplan–Meier survival analysis followed by log-rank test was used to estimate the difference in overall survival between patients with or without IPE.

Univariate and multivariable analysis was performed to determine the association between clinical variables and IPE; odds ratio (ORs) were calculated with 95% confidence intervals (CIs).

ResultsThe final analysis included 904 cases that were matched with 1808 controls (Table 1). The majority of cancer types were gastrointestinal, lung, lymphoma or breast cancer. Most patients (79.2%) had advanced cancer stage. Only one third of the patients had peripheral (segmental and subsegmental PE). Other incidental VTE was found in 189 (20.9%) patients as a concurrent finding. The 14 days mortality was significantly higher in patient with IPE compared to patients without (39 [4.3%] Vs 20 [1.1%], P <0.001). Also, patients with IPE had shorter overall survival (Figure 1).

In the multivariate analysis (Figure 2), patients on active treatment with chemotherapy or radiotherapy had higher risk of developing IPE (OR=2.23 [95%CI: 1.86-2.69], P<0.001) and (OR=4.12 [95%CI: 2.43-7.26], P<0.001) respectively. Similarly, higher risk was observed in patients with active cancer status (OR=4.46 [95%CI: 3.60-5.56], P<0.001) and in patients with cancer diagnosis confirmed within 6 months prior to presentation (OR=2.01 [95%CI: 1.66-2.42], P<0.001).

Characteristic No. of patients (%)

IPE No IPE Total 904 1808 Age, median (IQR) , years 63 (54-70) 63 (54-71) Sex

Female 412 (45.6) 841 (46.5) Male 492 (54.4) 967 (53.5)

Race/ethnicity Non-White 204 (22.6) 413 (22.8) White 700 (77.4) 1395 (77.2)

CCI , median (IQR) 6 (5-7) 6 (4-7) Cancer type

Gastrointestinal 266 (29.4) 498 (27.5) Lung 139 (15.4) 294 (16.3) Lymphoma 70 (7.7) 1 43 (7.9) Breast 69 (7.6) 143 (7.9) Urinary 68 (7.5) 144 (8.0) Others 292 (32.3) 586 (32.4)

Cancer stage Advanced 730 (80.8) 1419 (78.5) Local or hematologic 174 (19.2 ) 389 (21.5)

Active chemotherapy No 455 (50.3) 1295 (71.6) Yes 449 (49.7) 513 (28.4)

In the univariate analysis, active cancer status, active treatment with chemotherapy or radiotherapy and cancer diagnosis within 6 months of the presentation were all associated with IPE (Table 2).

Variable Univariate

OR (95% CI) P Time from cancer diagnosis

More than six months Six months or less 2.85 (2.40-3.39) <0.001

Cancer status Stable Active 6.17 (5.03-7.62) <0.001

Active chemotherapy No Yes 2.87 (2.42-3.40) <0.001

Active radiotherapy No Yes 5.41 (3.30-9.20) <0.001

Figure 2. Multivariable analysis of the association of cancer related risk factors and incidental pulmonary embolism

Sources of FundingThe study was funded by Bristol-Myer Squibb/Pfizer American Thrombosis Investigator Initiated Research Program (ARISTA-USA). The funder had no role in study design, data collection and analysis, or preparation of the manuscript.

P

0.5 1 2 5

Figure 1. Kaplan–Meier analysis for overall survival in patients with or without IPE

Table 1. Baseline characteristics of the cases and controls

Table 2. Univariate analysis of cancer-related riskfactors for incidental pulmonary embolism