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19-02-2024 | Mesothelioma | Peritoneal Surface Malignancy

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk

Authors: Varun V. Bansal, MBBS, Owen Mitchell, BS, Celyn Bregio, BA, Hunter D. D. Witmer, MD, MBA, Ankit Dhiman, MBBS, MS, Frederick A. Godley IV, MD, MS, MBA, Cecilia Ong, MD, Yaniv Berger, MD, Biren Reddy, BA, Jane E. Churpek, MD, MS, Michael W. Drazer, MD, PhD, Oliver S. Eng, MD, Hedy L. Kindler, MD, Kiran K. Turaga, MD, MPH, FACS

Published in: Annals of Surgical Oncology | Issue 5/2024

Abstract

Introduction

Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed.

Methods

Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively.

Results

Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02–0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9–67.0] vs. 55.0 months [CI 27.5–82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98).

Conclusions

A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

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Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–4. https://doi.org/10.1111/j.1538-7836.2007.02374.x.CrossRefPubMed

Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood. 2013;122(10):1712–23. https://doi.org/10.1182/blood-2013-04-460121.CrossRefPubMed

Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood. 2013;122(12):2011–8. https://doi.org/10.1182/blood-2013-04-460147.CrossRefPubMed

Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood. 2021;137(14):1959–69. https://doi.org/10.1182/blood.2020007338.CrossRefPubMed

Moik F, Ay C, Pabinger I. Risk prediction for cancer-associated thrombosis in ambulatory patients with cancer: past, present and future. Thromb Res. 2020;191(Suppl 1):S3–11. https://doi.org/10.1016/S0049-3848(20)30389-3.CrossRefPubMed

Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer–a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49(6):1404–13. https://doi.org/10.1016/j.ejca.2012.10.021.CrossRefPubMed

Kim J, Bhagwandin S, Labow DM. Malignant peritoneal mesothelioma: a review. Ann Transl Med. 2017;5(11):236. https://doi.org/10.21037/atm.2017.03.96.CrossRefPubMedPubMedCentral

Patel A, Anraku M, Darling GE, et al. Venous thromboembolism in patients receiving multimodality therapy for thoracic malignancies. J Thorac Cardiovasc Surg. 2009;138(4):843–8. https://doi.org/10.1016/j.jtcvs.2009.02.028.CrossRefPubMed

Koksal D, Safak O, Ozcan A, Agackiran Y, Erturk H, Findik G. Thromboembolic events in malignant pleural mesothelioma. Clin Appl Thromb Hemost. 2016;22(4):390–4. https://doi.org/10.1177/1076029614564861.CrossRefPubMed

10.

Nguyen D, Lee SJ, Libby E, Verschraegen C. Rate of thromboembolic events in mesothelioma. Ann Thorac Surg. 2008;85(3):1032–8. https://doi.org/10.1016/j.athoracsur.2007.11.064.CrossRefPubMed

11.

De León LE, Bravo-Iñiguez CE, Fox S, et al. Routine surveillance for diagnosis of venous thromboembolism after pleurectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2020;160(4):1064–73. https://doi.org/10.1016/j.jtcvs.2019.12.115.CrossRefPubMedPubMedCentral

12.

Cameron RB. Commentary: mesothelioma: the guinness world record holder in thromboembolism. J Thorac Cardiovasc Surg. 2020;160(4):1074–5. https://doi.org/10.1016/j.jtcvs.2019.12.082.CrossRefPubMed

13.

Antman KH, Pomfret EA, Aisner J, MacIntyre J, Osteen RT, Greenberger JS. Peritoneal mesothelioma: natural history and response to chemotherapy. J Clin Oncol. 1983;1(6):386–91. https://doi.org/10.1200/JCO.1983.1.6.386.CrossRefPubMed

14.

Ozkan M, Eser B, Er O, et al. Antiphospholipid syndrome associated with malignant mesothelioma presenting with superior vena cava thrombosis: a case report. Clin Appl Thromb Hemost. 2004;10(4):393–6. https://doi.org/10.1177/107602960401000413.CrossRefPubMed

15.

Ustündağ Y, Can U, Benli S, Büyükasik Y, Ozbek N. Internal carotid artery occlusion in a patient with malignant peritoneal mesothelioma: is it a sign of malignancy-related thrombosis? Am J Med Sci. 2000;319(4):265–7. https://doi.org/10.1097/00000441-200004000-00013.CrossRefPubMed

16.

Khan S, Kelly KJ, Veerapong J, Lowy AM, Baumgartner JM. Incidence, risk factors, and prevention strategies for venous thromboembolism after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2019;26(7):2276–84. https://doi.org/10.1245/s10434-019-07414-8.CrossRefPubMed

17.

Baumgartner JM, McKenzie S, Block S, Costantini TW, Lowy AM. Prophylactic enoxaparin doses may be inadequate in patients undergoing abdominal cancer surgery. J Surg Res. 2018;221:183–9. https://doi.org/10.1016/j.jss.2017.08.053.CrossRefPubMed

18.

Tuovila M, Erkinaro T, Takala H, et al. Hyperthermic intraperitoneal chemotherapy enhances blood coagulation perioperatively evaluated by thromboelastography: a pilot study. Int J Hyperth. 2020;37(1):293–300. https://doi.org/10.1080/02656736.2020.1742389.CrossRef

19.

Raghav K, Liu S, Overman MJ, et al. Efficacy, safety, and biomarker analysis of combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) blockade in advanced malignant peritoneal mesothelioma. Cancer Discov. 2021;11(11):2738–47. https://doi.org/10.1158/2159-8290.CD-21-0331.CrossRefPubMedPubMedCentral

20.

Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008;300(19):2277–85. https://doi.org/10.1001/jama.2008.656.CrossRefPubMed

21.

Paredes AZ, Abdel-Misih S, Schmidt C, Dillhoff ME, Pawlik TM, Cloyd JM. Predictors of readmission after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Surg Res. 2019;234:103–9. https://doi.org/10.1016/j.jss.2018.09.022.CrossRefPubMed

22.

Ghaferi AA, Schwartz TA, Pawlik TM. STROBE reporting guidelines for observational studies. JAMA Surgery. 2021;156(6):577–8. https://doi.org/10.1001/jamasurg.2021.0528.CrossRefPubMed

23.

Analytics, Insights, & Discovery | Epic. Available at: https://www.epic.com/software/analytics-insights-discovery. Accessed 5 Mar 2023.

24.

Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42. https://doi.org/10.1200/JCO.2009.23.9640.CrossRefPubMed

25.

Schuitevoerder D, Izquierdo FJ, Plana A, et al. The Chicago consensus on peritoneal surface malignancies: management of peritoneal mesothelioma. Ann Surg Oncol. 2020;27(6):1774–9. https://doi.org/10.1245/s10434-020-08324-w.CrossRef

26.

Hübner M, Kusamura S, Villeneuve L, et al. Guidelines for perioperative care in cytoreductive surgery (CRS) with or without hyperthermic IntraPEritoneal chemotherapy (HIPEC): enhanced recovery after surgery (ERAS^®) society recommendations–part I: preoperative and intraoperative management. Eur J Surg Oncol. 2020;46(12):2292–310. https://doi.org/10.1016/j.ejso.2020.07.041.CrossRefPubMed

27.

Dhiman A, Fenton E, Whitridge J, et al. Guide to enhanced recovery for cancer patients undergoing surgery: ERAS for patients undergoing cytoreductive surgery with or without HIPEC. Ann Surg Oncol. 2021;28(12):6955–64. https://doi.org/10.1245/s10434-021-09973-1.CrossRefPubMed

28.

Lundbech M, Krag AE, Iversen LH, Hvas AM. Postoperative bleeding and venous thromboembolism in colorectal cancer patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. Int J Colorectal Dis. 2022;37(1):17–33. https://doi.org/10.1007/s00384-021-04021-6.CrossRefPubMed

29.

Dranichnikov P, Mahteme H, Cashin PH, Graf W. Coagulopathy and venous thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2021;28(12):7772–82. https://doi.org/10.1245/s10434-021-09941-9.CrossRefPubMedPubMedCentral

30.

Lanuke K, Mack LA, Temple WJ. A prospective evaluation of venous thromboembolism in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Can J Surg. 2009;52(1):18–22.PubMedPubMedCentral

31.

Seng S, Liu Z, Chiu SK, et al. Risk of venous thromboembolism in patients with cancer treated with Cisplatin: a systematic review and meta-analysis. J Clin Oncol. 2012;30(35):4416–26. https://doi.org/10.1200/JCO.2012.42.4358.CrossRefPubMed

32.

Nakano T, Chahinian AP, Shinjo M, et al. Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma. Br J Cancer. 1998;77(6):907–12.CrossRefPubMedPubMedCentral

33.

Rottenstreich A, Kalish Y, Kleinstern G, Yaacov AB, Dux J, Nissan A. Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2017;116(7):914–20. https://doi.org/10.1002/jso.24746.CrossRefPubMed

34.

Ataseven B, du Bois A, Reinthaller A, et al. Pre-operative serum albumin is associated with post-operative complication rate and overall survival in patients with epithelial ovarian cancer undergoing cytoreductive surgery. Gynecol Oncol. 2015;138(3):560–5. https://doi.org/10.1016/j.ygyno.2015.07.005.CrossRefPubMed

35.

Folsom AR, Lutsey PL, Heckbert SR, Cushman M. Serum albumin and risk of venous thromboembolism. Thromb Haemost. 2010;104(1):100–4. https://doi.org/10.1160/TH09-12-0856.CrossRefPubMedPubMedCentral

36.

Königsbrügge O, Posch F, Riedl J, et al. Association between decreased serum albumin with risk of venous thromboembolism and mortality in cancer patients. Oncologist. 2016;21(2):252–7. https://doi.org/10.1634/theoncologist.2015-0284.CrossRefPubMedPubMedCentral

37.

Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost. 2005;94(2):362–5. https://doi.org/10.1160/TH05-04-0266.CrossRefPubMed

38.

Boussios S, Moschetta M, Karathanasi A, et al. Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives. Ann Gastroenterol. 2018;31(6):659–69. https://doi.org/10.20524/aog.2018.0305.CrossRefPubMedPubMedCentral

39.

Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499–506. https://doi.org/10.1182/blood-2017-03-743211.CrossRefPubMedPubMedCentral

40.

Connolly GC, Phipps RP, Francis CW. Platelets and cancer-associated thrombosis. Semin Oncol. 2014;41(3):302–10. https://doi.org/10.1053/j.seminoncol.2014.04.009.CrossRefPubMed

41.

Mason DP, Quader MA, Blackstone EH, et al. Thromboembolism after pneumonectomy for malignancy: an independent marker of poor outcome. J Thorac Cardiovasc Surg. 2006;131(3):711–8. https://doi.org/10.1016/j.jtcvs.2005.10.027.CrossRefPubMed

42.

Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343(25):1846–50. https://doi.org/10.1056/NEJM200012213432504.CrossRefPubMed

43.

Amer MH. Cancer-associated thrombosis: clinical presentation and survival. Cancer Manag Res. 2013;5:165–78. https://doi.org/10.2147/CMAR.S47094.CrossRefPubMedPubMedCentral

44.

Black D, Iasonos A, Ahmed H, Chi DS, Barakat RR, Abu-Rustum NR. Effect of perioperative venous thromboembolism on survival in ovarian, primary peritoneal, and fallopian tube cancer. Gynecol Oncol. 2007;107(1):66–70. https://doi.org/10.1016/j.ygyno.2007.05.040.CrossRefPubMed

45.

Akhtar-Danesh GG, Ben-Avi R, Agzarian J, Shargall Y. Is asymptomatic postoperative venous thromboembolism associated with long-term survival in patients undergoing lung resection for malignancy? JTCVS Open. 2021;6:241–5. https://doi.org/10.1016/j.xjon.2021.02.011.CrossRefPubMedPubMedCentral

46.

Anderson DR, Morgano GP, Bennett C, et al. American society of hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019;3(23):3898–944. https://doi.org/10.1182/bloodadvances.2019000975.CrossRefPubMedPubMedCentral

Title: Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk
Authors: Varun V. Bansal, MBBS
Owen Mitchell, BS
Celyn Bregio, BA
Hunter D. D. Witmer, MD, MBA
Ankit Dhiman, MBBS, MS
Frederick A. Godley IV, MD, MS, MBA
Cecilia Ong, MD
Yaniv Berger, MD
Biren Reddy, BA
Jane E. Churpek, MD, MS
Michael W. Drazer, MD, PhD
Oliver S. Eng, MD
Hedy L. Kindler, MD
Kiran K. Turaga, MD, MPH, FACS
Publication date: 19-02-2024
Publisher: Springer International Publishing
Keywords: Mesothelioma
Pleural Mesothelioma
Pleural Mesothelioma
Systemic Therapy
Phlebothrombosis
Published in: Annals of Surgical Oncology / Issue 5/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-024-15030-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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