Supportive Care in Cancer

, Volume 27, Issue 3, pp 921–925 | Cite as

External validation of three risk stratification rules in patients presenting with pulmonary embolism and cancer

  • Erin R. Weeda
  • Jonathan T. Caranfa
  • Gary H. Lyman
  • Nicole M. Kuderer
  • Elaine Nguyen
  • Craig I. Coleman
  • Christine G. KohnEmail author
Original Article


Numerous risk stratification rules exist to predict post-pulmonary embolism (PE) mortality; however, few were designed for use in cancer patients. In the EPIPHANY registry, adapted versions of common rules (the Hestia criteria, Pulmonary Embolism Severity Index [PESI], and simplified PESI [sPESI]) displayed high sensitivity for prognosticating mortality in PE patients with cancer. These adapted rules have yet to be externally validated. Therefore, we sought to evaluate the performance of an adapted Hestia criteria, PESI, and sPESI for predicting 30-day post-PE mortality in patients with cancer. We identified consecutive, adults presenting with objectively confirmed PE and cancer to our institution (November 2010 to January 2014). The proportion of patients categorized as low or high risk by these three risk stratification rules was calculated, and each rule’s accuracy for predicting 30-day all-cause mortality was determined. Of the 124 patients with PE and active cancer identified, 25 (20%) experienced mortality at 30 days. The adapted Hestia criteria categorized 23 (19%) patients as low risk, while exhibiting a sensitivity of 88% (95% confidence interval [CI] = 68–97%), a negative predictive value NPV of 87% (95% CI = 65–97%), and a specificity of 20% (95% CI = 13–30%). A total of 38 (31%) and 30 (24%) patients were low risk by the adapted PESI and sPESI, with both displaying sensitivities of 92% and NPVs > 93%. Specificities were 36% (95% CI = 27–47%) and 28% (95% CI = 20–38%) for PESI and sPESI. In our external validation, the adapted Hestia, PESI, and sPESI demonstrated high sensitivity but low specificity for 30-day PE mortality in patients with cancer. Larger, prospective trials are needed to optimize strategies for risk stratification in this population.


Mortality Pulmonary embolism Prognosis Risk assessment Severity of illness index 


Authors’ contributions

Study concept and design: ERW, CGK, CIC, and EN. Acquisition of data: ERW, CGK, JTC, CIC, and EN. Analysis and interpretation of data: ERW, CGK, JTC, CIC, and EN. Drafting the manuscript: ERW, CGK, JTC, GHL, NMK, CIC, and EN. Critical revision of the manuscript for important intellectual content: ERW, CGK, JTC, GHL, NMK, CIC, and EN. Administrative, technical, or material support: ERW, CGK, and CIC. Study supervision: CGK. CGK had full access to all the study data and take full responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICJME) and were fully responsible for all content and editorial decisions and were involved in all stages of the manuscript development.

Compliance with ethical standards

Conflicts of interest

CIC has received grant funding and consultancy fees from Janssen Scientific Affairs, LLC; Bayer Pharma AG; and Boehringer-Ingelheim Pharmaceuticals, Inc. ERW has received support for research from Pfizer Inc. NMK reports personal fees from Janssen, Myriad, Daiichi, Coherus, and Halozyme. No other authors have conflicts of interest germane to this manuscript.

Research involving human participants and/or animals/informed consent

This study was approved by the Institutional Review Board at our Institution. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent was not required.


  1. 1.
    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5:632–634CrossRefGoogle Scholar
  2. 2.
    Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149:315–352CrossRefGoogle Scholar
  3. 3.
    Konstantinides SV, Torbicki A, Agnelli G, Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) et al (2014) 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 35:3033–3069CrossRefGoogle Scholar
  4. 4.
    Kohn CG, Mearns ES, Parker MW, Hernandez AV, Coleman CI (2015) Prognostic accuracy of clinical prediction rules for early post-pulmonary embolism all-cause mortality: a bivariate meta-analysis. Chest 147:1043–1062CrossRefGoogle Scholar
  5. 5.
    Zondag W, den Exter PL, Crobach MJ, Dolsma A, Donker ML, Eijsvogel M, Faber LM, Hofstee HM, Kaasjager KA, Kruip MJ, Labots G, Melissant CF, Sikkens MS, Huisman MV, Hestia Study Investigators (2013) Hestia study investigators. Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism. Thromb Haemost 109:47–52CrossRefGoogle Scholar
  6. 6.
    Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ (2005) Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 172:1041–1046CrossRefGoogle Scholar
  7. 7.
    Jiménez D, Aujesky D, Moores L, Gómez V, Lobo JL, Uresandi F, Otero R, Monreal M, Muriel A, Yusen RD, RIETE Investigators (2010) Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 170:1383–1389CrossRefGoogle Scholar
  8. 8.
    Font C, Carmona-bayonas A, Fernández-martinez A et al (2014) Outpatient management of pulmonary embolism in cancer: data on a prospective cohort of 138 consecutive patients. J Natl Compr Cancer Netw 12:365–373CrossRefGoogle Scholar
  9. 9.
    Siragusa S, Arcara C, Malato A et al (2005) Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients. Ann Oncol 16(Suppl 4):iv136–iv139CrossRefGoogle Scholar
  10. 10.
    Carmona-bayonas A, Font C, Jiménez-fonseca P et al (2016) On the necessity of new decision-making methods for cancer-associated, symptomatic, pulmonary embolism. Thromb Res 143:76–85CrossRefGoogle Scholar
  11. 11.
    Kline JA, Roy PM, Than MP, Hernandez J, Courtney DM, Jones AE, Penaloza A, Pollack CV Jr (2012) Derivation and validation of a multivariate model to predict mortality from pulmonary embolism with cancer: the POMPE-C tool. Thromb Res 129:e194–e199CrossRefGoogle Scholar
  12. 12.
    Social Security Administration. Social Security Death Index, Master File. Social Security Administration. Available at: Accessed 2 Aug 2015
  13. 13.
    Ahn S, Lee YS, Kim WY, Lim KS, Lee JL (2016) Prognostic value of treatment setting in patients with cancer having pulmonary embolism: comparison with the pulmonary embolism severity index. Clin Appl Thromb Hemost 23:615–621. CrossRefGoogle Scholar
  14. 14.
    Den exter PL, Gómez V, Jiménez D et al (2013) A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer. Chest 143:138–145CrossRefGoogle Scholar
  15. 15.
    Weeda ER, Kohn CG, Peacock WF, Fermann GJ, Crivera C, Schein JR, Coleman CI (2017) External validation of the Hestia criteria for identifying acute pulmonary embolism patients at low risk of early mortality. Clin Appl Thromb Hemost 23:769–774CrossRefGoogle Scholar
  16. 16.
    Carmona-bayonas A, Jiménez-fonseca P, Font C et al (2017) Predicting serious complications in patients with cancer and pulmonary embolism using decision tree modelling: the EPIPHANY Index. Br J Cancer 116:994–1001CrossRefGoogle Scholar
  17. 17.
    Font C, Carmona-Bayonas A, Beato C, Reig Ò, Sáez A, Jiménez-Fonseca P, Plasencia JM, Calvo-Temprano D, Sanchez M, Benegas M, Biosca M, Varona D, Vicente MA, Faez L, Solís MP, de la Haba I, Antonio M, Madridano O, Castañon E, Martinez MJ, Marchena P, Ramchandani A, Dominguez A, Puerta A, Martinez de la Haza D, Pueyo J, Hernandez S, Fernandez-Plaza A, Martinez-Encarnacion L, Martin M, Marin G, Ayala F, Vicente V, Otero R (2017) Clinical features and short-term outcomes of cancer patients with suspected and unsuspected pulmonary embolism: the EPIPHANY study. Eur Respir J 49:1600282CrossRefGoogle Scholar
  18. 18.
    Posch F, Ay C (2017) Symptoms, signs, suspicion and setting: a PESI score for cancer-associated pulmonary embolism? Eur Respir J 49:1602225CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Erin R. Weeda
    • 1
  • Jonathan T. Caranfa
    • 2
  • Gary H. Lyman
    • 3
  • Nicole M. Kuderer
    • 4
  • Elaine Nguyen
    • 5
  • Craig I. Coleman
    • 6
  • Christine G. Kohn
    • 2
    • 6
    Email author
  1. 1.Medical University of South Carolina College of PharmacyCharlestonUSA
  2. 2.University of Connecticut School of MedicineFarmingtonUSA
  3. 3.Fred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.University of Washington School of MedicineSeattleUSA
  5. 5.Idaho State University College of PharmacyMeridianUSA
  6. 6.University of Connecticut/Hartford Hospital Evidence-Based Practice CenterHartfordUSA

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