How to treat incidental pulmonary embolism in cancer patients? Recent advances

Aurélien Delluc; Tzu-Fei Wang

doi:10.33963/KP.a2021.0164

Polish Heart Journal (Kardiologia Polska)
Vol 79, No 12 (2021) #87173 How to treat incidental pulmonary embolism in cancer patients? Recent advances

Vol 79, No 12 (2021)

Review paper

Published online: 2021-11-29

View PDF Download PDF file

Page views 7023

Article views/downloads 2053

Get Citation

Connect on Social Media

_04_HTML___KP_12_2021__Delluc

Review

How to treat incidental pulmonary embolism in cancer patients? Recent advances

Aurélien Delluc, Tzu-Fei Wang

Department of Medicine, Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

Correspondence to:

Aurélien Delluc, MD, PhD,

Department of Medicine,

Ottawa Hospital and Ottawa Hospital Research Institute,

University of Ottawa,

501 Smyth Road, Ottawa, ON K1H 8L6 Canada,

phone: +1 613 737 88 99,

e-mail: adelluc@toh.ca

Kardiol Pol. 2021; 79 (12): 1305–1310; DOI: 10.33963/KP.a2021.0164

Received: November 17, 2021

Revision accepted: November 29, 2021

Published online: November 29, 2021

Abstract

Patients with cancer have an increased risk of venous thromboembolism (VTE). In addition, due to the growing use of computed tomography scans in these patients and the improved scanners and imaging qualities, many cases of VTE are diagnosed incidentally on images obtained for reasons other than suspicion of VTE. Studies have shown that as many as half of all cancer-related pulmonary embolism (PE) cases could be incidental. Despite the common occurrence, the optimal management of incidental PE in patients with cancer remains unclear. This review will summarize pertinent literature related to incidental PE in the cancer population and discuss their outcomes and recommended treatments.

Key words: pulmonary embolism, venous thromboembolism, malignancy, cancer

Kardiol Pol 2021; 79, 12: 1305–1310

Introduction

Incidental pulmonary embolism (PE) refers to PE diagnosed in an asymptomatic or symptomatic patient undergoing imaging for reasons other than suspicion of PE. The incidence of incidental PE has been estimated to be in the range of 0.5% to 5.7% of chest computed tomography (CT) scans, depending on the population screened. Malignancy is the most frequent risk factor associated with incidental PE (39% of patients with unsuspected vs. 23% of patients with suspected PE had malignancy) [1]. Still, the clinical significance of incidental PE does not seem to differ according to the underlying risk factors [2]. Most recent data suggest approximately 50% of all cancer-related PE are detected on diagnostic imaging obtained for reasons other than suspicion of venous thromboembolism (VTE) [3, 4].

The increased use of CT scans in cancer patients and the introduction of multiple-detector CT scanners with their imaging quality that evolved over recent years have increased the incidence of incidental cancer-associated PE. In a recent systematic review and meta-analysis including 28 626 patients, the prevalence of incidental PE in cancer patients was 3.4% (95% confidence interval [CI], 3.2%–3.6%), with the lowest frequency observed in tumors of male reproductive organs (0.8%, 95% CI, 0.2%–1.4%) and the highest observed in patients with prostate cancer (8.6%, 95% CI 3.7%–13.4%) [5]. Several studies have evaluated the prognosis and the clinical course of incidental VTE in the cancer population, but the optimal management of these patients is still debated. Recent large randomized controlled trials (RCTs) evaluating direct oral anticoagulants (DOACs) as treatments for cancer-associated VTE included patients with incidental VTE and provided more insights into the outcomes of this population. Herein we will review pertinent literature related to incidental PE in the cancer population, summarize patient outcomes by different characteristics, discuss the screening process and recommended management.

Outcomes of incidental PE

Incidental vs. suspected

Historical trials in cancer-associated thrombosis, such as the CLOT trial, only included patients with symptomatic VTE [6]. More recent RCTs comparing DOAC to low-molecular-weight heparin (LMWH) in the treatment of cancer-associated thrombosis started to include patients with incidental VTE and provided important information regarding their outcomes. The Hokusai VTE Cancer trial (edoxaban vs. dalteparin, total 1046 patients) included 32.8% of patients with incidental VTE. In contrast, the SELECT-D trial had 27.8% (rivaroxaban vs. dalteparin, total 406 patients), and the Caravaggio trial had 19.9% (apixaban vs. dalteparin, total 1155 patients) of patients with incidental VTE [7–9].

In the Hokusai VTE Cancer trial, 331 patients (32.8%) had incidental VTE, and 679 (67.2%) had symptomatic VTE [10]. During the study period of 12 months, recurrent VTE was found in 7.9% in the incidental VTE group compared with 10.9% in the symptomatic VTE group (adjusted hazard ratio [HR], 0.68; 95% CI, 0.42–1.11). Major bleeding events were seen in 6.6% of those with incidental VTE and 4.9% with symptomatic VTE (HR, 1.22; 95% CI, 0.66–2.20). Similarly, in the Caravaggio trial, 230 (19.9%) patients had incidental VTE, and 925 (80.1%) had symptomatic VTE [11]. During the follow-up of 6 months, 4.3% and 7.4% of patients developed recurrent VTE in incidental and symptomatic VTE groups, retrospectively (HR, 0.57; 95% CI, 0.29–1.10). Major bleeding events occurred in 5.2% vs. 3.6% (incidental vs. symptomatic) (HR, 1.43, 95% CI, 0.74–2.77). Both trials showed that cases of incidental VTE were more likely to be PE (as compared to deep vein thrombosis [DVT]). They had less extensive extent and were more likely to be in patients with gastrointestinal cancer (less likely hematological cancer) and better Eastern Cooperative Oncology Group (ECOG) performance status (≤1). All these findings could have contributed to the differences in outcomes. Important differences in inclusion/exclusion criteria between both trials must also be highlighted when interpreting their results and before making clinical decisions. Unlike the Hokusai VTE Cancer and SELECT-D trials, the Caravaggio trial excluded patients with a primary brain tumor, known intracerebral metastases, or acute leukemia [7–9]. The decision to start anticoagulation for the treatment of acute VTE in patients with such conditions is extremely difficult, and strong evidence from trials is lacking. Although the Hokusai VTE Cancer and SELECT-D trials did not exclude these patients, the numbers enrolled were small, and it is likely those enrolled were deemed at lower bleeding risk.

To summarize the currently available literature, our group recently conducted a systematic review and meta-analysis to evaluate outcomes in cancer patients with incidentally detected VTE compared to those with suspected events [4]. Our eligibility criteria included studies that enrolled adult patients with cancer-associated VTE and reported the efficacy and safety of anticoagulation in patients with incidental and symptomatic index events. For the systematic review, we included 3 recent RCTs comparing DOAC to LMWH (SELECT-D, Hokusai VTE Cancer, and Caravaggio) and 20 observational studies. The meta-analysis of the 3 RCTs showed a significantly lower rate of recurrent VTE at 6 months in patients with incidental VTE than in those with symptomatic VTE (relative risk [RR], 0.62; 95% CI, 0.44–0.87). The 6-month risk of major bleeding events was numerically higher in those with incidental VTE compared to symptomatic VTE (RR, 1.47; 95% CI, 0.99–2.20). There was no difference in overall mortality. The reasons for differences in outcomes are unclear, but factors including different baseline characteristics (for example, patients with incidental VTE are more likely to have gastrointestinal malignancies and less likely to hematological ones) and acuity or type of PE (incidental PE could be tumor thrombus and/or subacute or chronic at the time of diagnosis). Among the 20 observational studies, there was one case-control study, four prospective, and 15 retrospective cohort studies. The proportion of patients with incidental cancer-associated VTE varied from 3.8% to 80.8%. In 16 of the 20 observational studies, the overall mortality was lower in patients with incidental events [4].

Symptomatic vs. asymptomatic

Numerous studies have suggested that many incidental PEs were, in fact, symptomatic. Thus the International Society on Thrombosis and Haemostasis (ISTH) strongly recommended using the term “incidental” instead of “asymptomatic” [12]. The entire pulmonary vasculature can be involved in incidentally diagnosed PE, ranging from isolated sub-segmental PE (SSPE) to lobar or main pulmonary branches, which explains why not all affected patients are symptomatic. Nevertheless, patients diagnosed with incidental PE are often symptomatic, although symptoms could be missed or misattributed. A recent prospective cohort study of 695 patients with cancer-associated incidental PE revealed that typical signs and symptoms consistent with PE had been present within 14 days before incidental PE diagnosis in 44% of the cases [13]. Many PE symptoms (chest pain, shortness of breath) are non-specific and can often be attributed to malignancy itself and/or cancer therapies and may be missed or not perceived as related to VTE by patients and/or clinicians.

Furthermore, the presence of symptoms in cancer patients with incidental PE should not be overlooked as they could be associated with important outcomes such as mortality. The EPIPHANY study evaluated outcomes stratified by the presence of symptoms in patients with incidental cancer-associated PE [14]. In total, 497 patients were prospectively assessed for symptoms. One hundred and fifty-four had truly asymptomatic incidental PE, 129 had symptomatic incidental PE, and 214 had suspected PE. Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups. However, the overall 30-day mortality rate was significantly lower in patients with truly asymptomatic incidental PE events (3%) than in those with symptomatic incidental PE (20%) or suspected PE (21%) (P <0.0001). Another study by O’Connell et al. [15, 16] revealed that in patients with cancer and unsuspected VTE, survival was significantly reduced in those with symptomatic events compared to those who were truly asymptomatic (P = 0.002). In the above-mentioned prospective cohort study of 695 ambulatory cancer patients with unsuspected PE, respiratory symptoms within 14 days prior to the diagnosis of PE and ECOG performance status were the two most important predictors for overall survival in this population [17]. These data suggest the importance of carefully assessing symptoms in cancer patients, including those that might not typically be thought of as related to PE (such as fatigue).

Treated vs. untreated VTE

Current guidelines recommend therapeutic anticoagulation for incidental VTE as one would have done for symptomatic VTE (Table 1), so most incidental PEs are treated with anticoagulation.

Table 1. Summary of major guideline recommendations on treatment of incidental PE and SSPE

	Incidental PE	SSPE
ACCP 2012, 2016, and 2021	Same initial and long-term anticoagulation as for comparable patients with symptomatic PE (grade 2B)	The presence of cancer may favor choosing anticoagulation or more aggressive surveillance (such as serial venous ultrasound)
ASCO 2020	Should be treated in the same manner as symptomatic VTE	Treatment determined individually
ASH 2021	Conditional recommendation of short-term treatment (3–6 months)	Conditional recommendation of short-term treatment (3–6 months)

Abbreviations: ACCP, American College of Chest Physicians; ASCO, American Society of Clinical Oncology; ASH, American Society of Hematology; PE, pulmonary embolism; SSPE, subsegmental pulmonary embolism

The literature reports that more than 90% of patients with incidental VTE receive therapeutic anticoagulation. Hence, data on outcomes in patients not treated with anticoagulation remained very limited and often biased towards those with poorer prognoses [4]. An individual patient data meta-analysis from 11 registries shed some light on the outcomes of cancer-associated incidental PE when patients were left untreated [18]. Of the 926 patients in the study, 53 (5.7%) never received anticoagulation. Their 6-month VTE recurrence risk was 12%, twice as high as for patients treated with anticoagulants. Although it is possible that these patients were left untreated for specific reasons, the patient characteristics did not differ from those of treated patients. In patients who did not receive any treatment, the weighted pooled 6-month mortality was 47% (95% CI, 28%–66%), as compared with 37% (95% CI, 29%–44%) in patients treated with LMWH and 28% (95% CI, 18%–40%) in those treated with vitamin K antagonists.

Subsegmental pulmonary embolism

The thinner slices of CT scans allow a better description of smaller arteries. In a prospective longitudinal cohort study of oncological patients who had a chest CT for reasons other than suspicion of PE, the prevalence of incidental PE was noted to be 4.4% [19]. A 64-multi detector CT scan with a 5 mm slice was compared to a 1–1.5 mm slice reconstruction for pulmonary arteries assessment, and it turned out that almost 40% of all PE were only detected using the 1 mm thickness [19]. Interestingly, such as symptomatic PEs, this increased number of PE diagnosis seen in different studies seemed to principally involve peripheral, segmental, and subsegmental pulmonary arteries [19–22]. However, the true prevalence and thrombosis load are uncertain in the context of potentially suboptimal pulmonary arteries opacification of a CT scan not dedicated to PE detection [3, 18, 23, 24].

The clinical significance of SSPE in the absence of DVT is a matter of debate, and management strategies differ among physicians. Studies assessing the safety of withholding anticoagulation in non-cancer patients are ongoing (NCT01455818, NCT04263038). “A preliminary” report of one of these studies suggested elderly patients (age ≥65 years) and those with multiple SSPE had a higher risk of VTE recurrence during the 3-month follow-up when anticoagulation was withheld [25]. It is worth noting that patients with cancer were excluded from this study.

Subgroup analyses of other studies involving cancer patients with unsuspected PE suggested that patients with SSPE had a similar prognosis compared to the ones with more proximal PEs, with 12-month VTE recurrence rates of 6.4% and 6.0%, respectively (P = 0.93) and 12-month mortality rates of 49.9% and 58.2% (P = 0.34), respectively [13]. In another single-center retrospective study of 206 patients with SSPE and active cancer, the majority (67%) of SSPE cases were incidental, and most (88.3%) were treated with anticoagulation [26]. During the 12-month follow-up, 8.7% had recurrent PE, 5.3% had major bleeding by ISTH criteria, and 7.3% had non-major bleeding events. All bleeding events occurred in patients on anticoagulants. Patients treated with anticoagulation had a numerically lower PE recurrence rate than those who were not (8% vs. 13%; P = 0.58). Multivariable analysis showed that only poor ECOG performance status and stage IV disease (not anticoagulation use) were associated with worsened survival in this population. Therefore, the optimal treatment in incidental SSPE in the cancer population remains unclear. Currently, in clinical practice, many providers are likely to provide anticoagulation in the absence of bleeding concerns.

Screening for asymptomatic VTE

As the presence of VTE may impact cancer prognosis, one can hypothesize that early detection of VTE may be beneficial for patients. However, the practice of routine screening to detect asymptomatic VTE remains controversial and is not standard of care. In a study of 62 unselected ambulatory lung cancer and lymphoma patients, none were found to have DVT on screening ultrasound before starting chemotherapy [27]. Another study of 32 patients deemed at high risk of VTE (Khorana score ≥3) found 3 cases (9.3%) of asymptomatic DVT at baseline [28]. A more recent retrospective analysis of PHACS (Prophylaxis of High-Risk Ambulatory Cancer Patients Study) similarly showed a 9% prevalence of incidental VTE in 117 asymptomatic patients with Khorana score ≥3 [29]. In a prospective cohort study, incidental VTE was systematically screened with chest-abdomen-pelvic CT scans and whole-leg compression ultrasonography in 97 cancer patients before starting chemotherapy and again after 3 months [30]. VTE was detected in 29 patients (31%), of whom 14 (14%) had isolated distal DVT and 2 (2%) had PE. More recently, the CASSINI trial performed screening lower limb ultrasound prior to randomization [31]. The CASSINI trial is an RCT comparing low-dose rivaroxaban or placebo for primary prevention of VTE in ambulatory patients starting a systemic cancer therapy and at intermediate-to-high risk of VTE (Khorana score ≥2) [31]. Of the 1080 patients initially enrolled in the trial, 49 (4.5%) were found to have a proximal DVT of the lower limbs on a screening compression ultrasonography and were not randomized. Despite these reports of screen-detected DVT, the clinical significance of these incidental DVTs detected on screening ultrasonography has never been assessed. Furthermore, the cost-effectiveness of these screening approaches requires further evaluation. Therefore, there is no evidence to suggest CT screening as routine in clinical practice at this time.

Management of incidental PE

Management of incidental PE follows a 3-step approach: confirm, assess for bleeding risk, and determine treatment strategies. The first step in managing incidental PE is to confirm the diagnosis. This is especially important in the case of SSPE due to the potential high disagreement among radiologists on the true presence of a thrombus [32]. In addition, incidental PE is typically diagnosed on a routine CT scan used for cancer staging and not a dedicated CT pulmonary angiogram. When in doubt, repeating imaging with a dedicated CT pulmonary angiogram and/or requesting a second opinion to review the imaging are recommended. Evaluation of signs and symptoms of a concurrent lower limb DVT may also assist in achieving diagnostic and treatment clarity. Once the presence of PE is confirmed, assessment for bleeding risks is important before initiation of anticoagulation. This is especially crucial for patients with cancer, as they have a heightened risk of bleeding due to anti-cancer therapies, potential thrombocytopenia, and/or vessel invasion by the malignancy.

Regarding treatment, several international guidelines have emphasized the absence of good quality evidence for the management of incidental PE. Still, currently, all major guidelines suggest the same initial and long-term anticoagulation management strategies as for comparable patients with symptomatic PE (Table 1). The American College of Chest Physicians (ACCP) guidelines graded this recommendation 2B in 2012 (i.e. weak recommendation, moderate-quality evidence), did not mention incidental PE in the first update in 2016 and did not modify the recommendation in the second update in 2021 [33–35]. Based on expert consensus, the American Society of Clinical Oncology (ASCO) guidelines recommended that incidental PE and DVT be treated similarly to symptomatic VTE [36]. Treatment for incidental SSPE should be determined individually, weighing risks and benefits of anticoagulation, as there is insufficient evidence. The American Society of Hematology (ASH) provided a conditional recommendation for short-term treatment (3–6 months) under observation for patients with incidental PE as well as SSPE, acknowledging very low certainty from available evidence [37]. Practically, we manage patients with incidental cancer-associated PE in the same manner as suspected ones. We prefer using DOACs for patients at low risk of bleeding and with no potential drug-drug interactions with current systemic therapy [38]. In patients at high risk of bleeding (e.g. patients with luminal gastrointestinal cancerwith an intact primary tumor, patients with uterus, renal, or bladder cancers), we usually initiate anticoagulation with LMWH. We follow the approved regimens for each drug (Table 2) and decide on treatment duration and dose reduction on a case-by-case basis. The currently ongoing API-CAT study (NCT03692065) is an RCT aiming to assess the use of low-dose apixaban for extended anticoagulation after an initial 6 months of treatment in patients with cancer-associated VTE [39]. Patients with an incidental index event are eligible for this trial, which soon will provide more insight on the optimal management of these patients in the long term.

Table 2. Approved anticoagulation regimens in patients with a creatinine clearance greater than 30 ml/min

Direct oral anticoagulants
Apixaban	10 mg twice daily for 7 days, then 5 mg twice daily
Edoxaban	5-day lead-in with parenteral anticoagulant followed by 60 mg once dailya
Rivaroxaban	15 mg twice daily for 21 days, then 20 mg once daily
Low-molecular-weight heparins
Dalteparin	200 IU/kg of body weight once daily for 28 days, then 150 IU/kg once daily
Enoxaparin	1 mg/kg of body weight twice daily or 1.5 mg/kg once daily
Tinzaparin	175 IU/kg of body weight once daily

aDose reduction to 30 mg once daily in patients with a creatinine clearance of 30 to 50 ml/min, or body weight of 60 kg or less, or in those receiving concomitant treatment with potent P-glycoprotein inhibitors

Conclusions

To conclude, incidental PE is frequently encountered in patients with cancer. Given the risk of recurrent VTE in this population, guidelines recommend the same anticoagulation management as for symptomatic VTE, which is routinely done in clinical practice. However, recent RCTs indicate a lower risk of recurrent VTE and a higher risk of bleeding events in cancer patients with incidental VTE compared to symptomatic ones. This discrepancy is likely to be due to different patient populations involved and other differences in baseline characteristics. It is important to keep these in mind in the design of future clinical trials as they may be an important stratifying factor that can affect outcomes.

Article information

Conflict of interest: AD reports grants from Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. T-FW reports research funding from Leo Pharma and advisory honoraria from Servier. AD and T-FW are both recipients of a University of Ottawa Department of Medicine research award.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.

How to cite: Delluc A, Wang T-F. How to treat incidental pulmonary embolism in cancer patients? Recent advances. Kardiol Pol. 2021; 79(12): 1305–1310, doi: 10.33963/KP.a2021.0164.

REFERENCES

1. Shteinberg M, Segal-Trabelsy M, Adir Y, et al. Clinical characteristics and outcomes of patients with clinically unsuspected pulmonary embolism versus patients with clinically suspected pulmonary embolism. Respiration. 2012; 84(6): 492–500, doi: 10.1159/000342324, indexed in Pubmed: 22986339.
2. Spirk D, Sebastian T, Barco S, et al. Clinical outcomes of incidental venous thromboembolism in cancer and noncancernoncancer patients: The SWiss Venous ThromboEmbolism Registry (SWIVTER). Thromb Haemost. 2021; 121(5): 641–649, doi: 10.1055/s-0040-1720977, indexed in Pubmed: 33202448.
3. van Es N, Bleker SM, Di Nisio M. Cancer-associated unsuspected pulmonary embolism. Thromb Res. 2014; 133 Suppl 2: S172–S178, doi: 10.1016/S0049-3848(14)50028-X, indexed in Pubmed: 24862140.
4. Caiano L, Carrier M, Marshall A, et al. Outcomes among patients with cancer and incidental or symptomatic venous thromboembolism: A systematic review and meta-analysis. J Thromb Haemost. 2021; 19(10): 2468–2479, doi: 10.1111/jth.15435, indexed in Pubmed: 34161655.
5. Meyer HJ, Wienke A, Surov A. Incidental pulmonary embolism in oncologic patients-a systematic review and meta-analysis. Support Care Cancer. 2021; 29(3): 1293–1302, doi: 10.1007/s00520-020-05601-y, indexed in Pubmed: 32621266.
6. Lee AYY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003; 349(2): 146–153, doi: 10.1056/NEJMoa025313, indexed in Pubmed: 12853587.
7. Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020; 382(17): 1599–1607, doi: 10.1056/NEJMoa1915103, indexed in Pubmed: 32223112.
8. Kraaijpoel N, Di Nisio M, Mulder FI, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018; 378(7): 615–624, doi: 10.1056/NEJMoa1711948, indexed in Pubmed: 29231094.
9. Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral factor xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018; 36(20): 2017–2023, doi: 10.1200/JCO.2018.78.8034, indexed in Pubmed: 29746227.
10. Mulder FI, Di Nisio M, Ay C, et al. Clinical implications of incidental venous thromboembolism in cancer patients. Eur Respir J. 2020; 55(2), doi: 10.1183/13993003.01697-2019, indexed in Pubmed: 31727694.
11. Giustozzi M, Connors JM, Ruperez Blanco AB, et al. Clinical characteristics and outcomes of incidental venous thromboembolism in cancer patients: Insights from the Caravaggio study. J Thromb Haemost. 2021; 19(11): 2751–2759, doi: 10.1111/jth.15461, indexed in Pubmed: 34260816.
12. Khorana AA, O’Connell C, Agnelli G, et al. Incidental venous thromboembolism in oncology patients. J Thromb Haemost. 2012; 10(12): 2602–2604, doi: 10.1111/jth.12023, indexed in Pubmed: 23362525.
13. Kraaijpoel N, Bleker SM, Meyer G, et al. Treatment and long-term clinical outcomes of incidental pulmonary embolism in patients with cancer: an international prospective cohort study. J Clin Oncol. 2019; 37(20): 1713–1720, doi: 10.1200/JCO.18.01977, indexed in Pubmed: 31116676.
14. Font C, Carmona-Bayonas A, Beato C, et al. Clinical features and short-term outcomes of cancer patients with suspected and unsuspected pulmonary embolism: the EPIPHANY study. Eur Respir J. 2017; 49(1), doi: 10.1183/13993003.00282-2016, indexed in Pubmed: 28052954.
15. O’Connell CL, Boswell WD, Duddalwar V, et al. Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. J Clin Oncol. 2006; 24(30): 4928–4932, doi: 10.1200/JCO.2006.06.5870, indexed in Pubmed: 17050877.
16. O’Connell CL, Razavi PA, Liebman HA. Symptoms adversely impact survival among patients with cancer and unsuspected pulmonary embolism. J Clin Oncol. 2011; 29(31): 4208–9; author reply 4209, doi: 10.1200/JCO.2011.37.2730, indexed in Pubmed: 21969510.
17. Maraveyas A, Kraaijpoel N, Bozas G, et al. The prognostic value of respiratory symptoms and performance status in ambulatory cancer patients and unsuspected pulmonary embolism; analysis of an international, prospective, observational cohort study. J Thromb Haemost. 2021; 19(11): 2791–2800, doi: 10.1111/jth.15489, indexed in Pubmed: 34532927.
18. van der Hulle T, den Exter PL, Planquette B, et al. Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients. J Thromb Haemost. 2016; 14(1): 105–113, doi: 10.1111/jth.13172, indexed in Pubmed: 26469193.
19. Browne AM, Cronin CG, English C, et al. Unsuspected pulmonary emboli in oncology patients undergoing routine computed tomography imaging. J Thorac Oncol. 2010; 5(6): 798–803, doi: 10.1097/JTO.0b013e3181d6153a, indexed in Pubmed: 20421822.
20. Auer RC, Schulman AR, Tuorto S, et al. Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. J Am Coll Surg. 2009; 208(5): 871–878, doi: 10.1016/j.jamcollsurg.2008.12.030, indexed in Pubmed: 19476851.
21. Jia CF, Li YX, Yang ZQ, et al. Prospective evaluation of unsuspected pulmonary embolism on coronary computed tomographic angiography. J Comput Assist Tomogr. 2012; 36(2): 187–190, doi: 10.1097/RCT.0b013e3182483be1, indexed in Pubmed: 22446357.
22. Ritchie G, McGurk S, McCreath C, et al. Prospective evaluation of unsuspected pulmonary embolism on contrast enhanced multidetector CT (MDCT) scanning. Thorax. 2007; 62(6): 536–540, doi: 10.1136/thx.2006.062299, indexed in Pubmed: 17158631.
23. Di Nisio M, Carrier M. Incidental venous thromboembolism: is anticoagulation indicated? Hematology Am Soc Hematol Educ Program. 2017; 2017(1): 121–127, doi: 10.1182/asheducation-2017.1.121, indexed in Pubmed: 29222246.
24. Klok FA, Huisman MV, van der Hulle T, et al. Physicians’ management approach to an incidental pulmonary embolism: an international survey. J Thromb Haemost. 2013; 11(1): 208–213, doi: 10.1111/jth.12040, indexed in Pubmed: 23088591.
25. Le Ga, Kovacs M, Couturaud F, et al. The Management of SubSegmental Pulmonary Embolism without Anticoagulation [abstract]. Res Pract Thromb Haemost. 2021; 5(Suppl 2).
26. Yan M, Kieser R, Wu CC, et al. Clinical factors and outcomes of subsegmental pulmonary embolism in cancer patients. Blood Adv. 2021; 5(4): 1050–1058, doi: 10.1182/bloodadvances.2020003136, indexed in Pubmed: 33599740.
27. Bernstein R, Haim N, Brenner B, et al. Venous sonography for the diagnosis of asymptomatic deep vein thrombosis in patients with cancer undergoing chemotherapy. J Ultrasound Med. 2004; 23(5): 655–658, doi: 10.7863/jum.2004.23.5.655, indexed in Pubmed: 15154532.
28. Khorana AA, Rubens D, Francis CW. Screening high-risk cancer patients for VTE: a prospective observational study. Thromb Res. 2014; 134(6): 1205–1207, doi: 10.1016/j.thromres.2014.09.016, indexed in Pubmed: 25288468.
29. Loftus JR, Hu Z, Morin BR, et al. Vascular imaging in the asymptomatic high-risk cancer population: a role for thrombosis screening and therapy management. J Ultrasound Med. 2021 [Epub ahead of print], doi: 10.1002/jum.15701, indexed in Pubmed: 33772825.
30. Kitayama H, Kondo T, Sugiyama J, et al. Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study. BMC Cancer. 2017; 17(1): 351, doi: 10.1186/s12885-017-3326-1, indexed in Pubmed: 28525975.
31. Khorana AA, McNamara MG, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019; 380(8): 720–728, doi: 10.1056/NEJMoa1814630, indexed in Pubmed: 30786186.
32. Pena E, Kimpton M, Dennie C, et al. Difference in interpretation of computed tomography pulmonary angiography diagnosis of subsegmental thrombosis in patients with suspected pulmonary embolism. J Thromb Haemost. 2012; 10(3): 496–498, doi: 10.1111/j.1538-7836.2011.04612.x, indexed in Pubmed: 22212300.
33. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl): e419S–e496S, doi: 10.1378/chest.11-2301, indexed in Pubmed: 22315268.
34. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016; 149(2): 315–352, doi: 10.1016/j.chest.2015.11.026, indexed in Pubmed: 26867832.
35. Stevens SM, Woller SC, Baumann Kreuziger L, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021 [Epub ahead of print], doi: 10.1016/j.chest.2021.07.055, indexed in Pubmed: 34352278.
36. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020; 38(5): 496–520, doi: 10.1200/JCO.19.01461, indexed in Pubmed: 31381464.
37. Lyman GH, Carrier M, Ay C, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021; 5(4): 927–974, doi: 10.1182/bloodadvances.2020003442, indexed in Pubmed: 33570602.
38. Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost. 2018; 16(9): 1891–1894, doi: 10.1111/jth.14219, indexed in Pubmed: 30027649.
39. Mahé I, Agnelli G, Ay C, et al. Extended anticoagulant treatment with full- or reduced-dose apixaban in patients with cancer-associated venous thromboembolism: rationale and design of the API-CAT study. Thromb Haemost. 2021 [Epub ahead of print], doi: 10.1055/a-1647-9896, indexed in Pubmed: 34535037.

Polish Heart Journal (Kardiologia Polska)

About Via Medica Advertising

Bookstore (Ikamed) TVMed

News