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Independent and incremental value of ventilation/perfusion PET/CT and CT pulmonary angiography for pulmonary embolism diagnosis: results of the PECAN pilot study

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Abstract

Purpose

This pilot study assessed the independent and incremental value of 68Ga-V/Q PET/CT as compared with CT pulmonary angiography (CTPA) for the management of cancer patients with suspected acute pulmonary embolism (PE).

Methods

All 24 cancer patients with suspected acute PE prospectively recruited underwent both 68Ga-V/Q PET/CT and CTPA within 24 h. PET/CT was acquired after inhalation of Galligas prepared using a Technegas generator and administration of 68Ga-macroaggregated albumin. Initially, PET/CT and CTPA scans were read independently with the reader blinded to the results of the other imaging study. CTPA and PET/CT were then coregistered and reviewed by consensus between a radiologist and nuclear medicine physician. The therapeutic management was established by the managing physician based on all available data.

Results

The diagnostic conclusion was concordantly negative in 18 patients (75%). Of the six discordant diagnoses on independent reading, combined interpretation of V/Q PET/CTPA enabled a consensus conclusion in two patients, excluding PE in one and confirming PE in the other, similar to the initial diagnostic conclusion of the V/Q PET/CT. Of the remaining four patients, three had a single subsegmental thrombus on CTPA but a negative V/Q PET/CT scan, and two of these did not receive long-term anticoagulation and did not have a venous thromboembolic event during a 3-year follow-up period. The third patient, along with a patient with a positive V/Q PET/CT scan but a negative CTPA scan, presented with acute complications preventing any conclusions with regard to the appropriateness of the V/Q PET/CT results in the management of PE. Overall, V/Q PET had an impact on management in four patients (17%).

Conclusion

In this pilot study, we demonstrated the feasibility and potential utility of V/Q PET/CT for the management of patients with suspected PE. V/Q PET/CT may be of particular relevance in patients with equivocal findings or isolated subsegmental findings on CTPA, adding further discriminatory information to allow important decision-making regarding the use or withholding of anticoagulation. Given the other advantages of V/Q PET/CT (reduced acquisition time, low radiation dose), and with the increasing availability of 68Ga generators, PET/CT is a potential replacement for V/Q SPECT/CT imaging.

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References

  1. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960;1(7138):1309–12.

    Article  CAS  PubMed  Google Scholar 

  2. Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010;152(9):578–89. https://doi.org/10.7326/0003-4819-152-9-201005040-00008.

    Article  PubMed  Google Scholar 

  3. Kuderer NM, Ortel TL, Francis CW. Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. J Clin Oncol. 2009;27(29):4902–11. https://doi.org/10.1200/JCO.2009.22.4584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166(4):458–64. https://doi.org/10.1001/archinte.166.4.458.

    Article  PubMed  Google Scholar 

  5. Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–8. https://doi.org/10.1182/blood-2002-01-0108.

    Article  CAS  PubMed  Google Scholar 

  6. Douketis JD, Crowther MA, Foster GA, Ginsberg JS. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis? Am J Med. 2001;110(7):515–9.

    Article  CAS  PubMed  Google Scholar 

  7. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743–53. https://doi.org/10.1001/jama.298.23.2743.

    Article  CAS  PubMed  Google Scholar 

  8. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831–7. https://doi.org/10.1001/archinternmed.2011.178.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ. 2013;347:f3368. https://doi.org/10.1136/bmj.f3368.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sheh SH, Bellin E, Freeman KD, Haramati LB. Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT? AJR Am J Roentgenol. 2012;198(6):1340–5. https://doi.org/10.2214/AJR.11.6426.

    Article  PubMed  Google Scholar 

  11. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315–52. https://doi.org/10.1016/j.chest.2015.11.026.

    Article  PubMed  Google Scholar 

  12. Salaun PY, Couturaud F, Le Duc-Pennec A, Lacut K, Le Roux PY, Guillo P, et al. Noninvasive diagnosis of pulmonary embolism. Chest. 2011;139(6):1294–8. https://doi.org/10.1378/chest.10-1209.

    Article  PubMed  Google Scholar 

  13. Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb Haemost. 2007;5(Suppl 1):41–50. https://doi.org/10.1111/j.1538-7836.2007.02493.x.

    Article  CAS  PubMed  Google Scholar 

  14. Le Roux PY, Robin P, Delluc A, Abgral R, Le Duc-Pennec A, Nowak E, et al. V/Q SPECT interpretation for pulmonary embolism diagnosis: which criteria to use? J Nucl Med. 2013;54(7):1077–81. https://doi.org/10.2967/jnumed.112.113639.

    Article  CAS  PubMed  Google Scholar 

  15. Le Duc-Pennec A, Le Roux PY, Cornily JC, Jaffrelot M, Delluc A, de Saint-Martin L, et al. Diagnostic accuracy of single-photon emission tomography ventilation/perfusion lung scan in the diagnosis of pulmonary embolism. Chest. 2012;141(2):381–7. https://doi.org/10.1378/chest.11-0090.

    Article  PubMed  Google Scholar 

  16. Le Roux PY, Palard X, Robin P, Delluc A, Abgral R, Querellou S, et al. Safety of ventilation/perfusion single photon emission computed tomography for pulmonary embolism diagnosis. Eur J Nucl Med Mol Imaging. 2014;41(10):1957–64. https://doi.org/10.1007/s00259-014-2763-1.

    Article  PubMed  Google Scholar 

  17. Le Roux PY, Robin P, Delluc A, Abgral R, Palard X, Tissot V, et al. Additional value of combining low-dose computed tomography to V/Q SPECT on a hybrid SPECT-CT camera for pulmonary embolism diagnosis. Nucl Med Commun. 2015;36(9):922–30. https://doi.org/10.1097/MNM.0000000000000351.

    Article  PubMed  Google Scholar 

  18. Gutte H, Mortensen J, Jensen CV, Johnbeck CB, von der Recke P, Petersen CL, et al. Detection of pulmonary embolism with combined ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector CT angiography. J Nucl Med. 2009;50(12):1987–92. https://doi.org/10.2967/jnumed.108.061606.

    Article  PubMed  Google Scholar 

  19. Hicks RJ, Hofman MS. Is there still a role for SPECT-CT in oncology in the PET-CT era? Nat Rev Clin Oncol. 2012;9(12):712–20. https://doi.org/10.1038/nrclinonc.2012.188.

    Article  CAS  PubMed  Google Scholar 

  20. Oehme L, Zophel K, Golgor E, Andreeff M, Wunderlich G, Brogsitter C, et al. Quantitative analysis of regional lung ventilation and perfusion PET with (68)Ga-labelled tracers. Nucl Med Commun. 2014;35(5):501–10. https://doi.org/10.1097/MNM.0000000000000084.

    Article  CAS  PubMed  Google Scholar 

  21. Le Roux PY, Robin P, Salaun PY. New developments and future challenges of nuclear medicine and molecular imaging for pulmonary embolism. Thromb Res. 2018;163:236–41. https://doi.org/10.1016/j.thromres.2017.06.031.

    Article  CAS  PubMed  Google Scholar 

  22. Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015;35(2):500–16. https://doi.org/10.1148/rg.352140164.

    Article  PubMed  Google Scholar 

  23. Hofman MS, Beauregard JM, Barber TW, Neels OC, Eu P, Hicks RJ. 68Ga PET/CT ventilation-perfusion imaging for pulmonary embolism: a pilot study with comparison to conventional scintigraphy. J Nucl Med. 2011;52(10):1513–9. https://doi.org/10.2967/jnumed.111.093344.

    Article  CAS  PubMed  Google Scholar 

  24. Le Roux PY, Hicks RJ, Siva S, Hofman MS. PET/CT lung ventilation and perfusion scanning using Galligas and gallium-68-MAA. Semin Nucl Med. 2019;49(1):71–81. https://doi.org/10.1053/j.semnuclmed.2018.10.013.

    Article  PubMed  Google Scholar 

  25. Le Roux PY, Siva S, Steinfort DP, Callahan J, Eu P, Irving LB, et al. Correlation of 68Ga ventilation-perfusion PET/CT with pulmonary function test indices for assessing lung function. J Nucl Med. 2015;56(11):1718–23. https://doi.org/10.2967/jnumed.115.162586.

    Article  CAS  PubMed  Google Scholar 

  26. Le Roux PY, Siva S, Callahan J, Claudic Y, Bourhis D, Steinfort DP, et al. Automatic delineation of functional lung volumes with (68)Ga-ventilation/perfusion PET/CT. EJNMMI Res. 2017;7(1):82. https://doi.org/10.1186/s13550-017-0332-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hardcastle N, Hofman MS, Hicks RJ, Callahan J, Kron T, MacManus MP, et al. Accuracy and utility of deformable image registration in (68)Ga 4D PET/CT assessment of pulmonary perfusion changes during and after lung radiation therapy. Int J Radiat Oncol Biol Phys. 2015;93(1):196–204. https://doi.org/10.1016/j.ijrobp.2015.05.011.

    Article  PubMed  Google Scholar 

  28. Siva S, Thomas R, Callahan J, Hardcastle N, Pham D, Kron T, et al. High-resolution pulmonary ventilation and perfusion PET/CT allows for functionally adapted intensity modulated radiotherapy in lung cancer. Radiother Oncol. 2015;115(2):157–62. https://doi.org/10.1016/j.radonc.2015.04.013.

    Article  PubMed  Google Scholar 

  29. Siva S, Hardcastle N, Kron T, Bressel M, Callahan J, MacManus MP, et al. Ventilation/perfusion positron emission tomography-based assessment of radiation injury to lung. Int J Radiat Oncol Biol Phys. 2015;93(2):408–17. https://doi.org/10.1016/j.ijrobp.2015.06.005.

    Article  PubMed  Google Scholar 

  30. Leong P, Le Roux PY, Callahan J, Siva S, Hofman MS, Steinfort DP. Reduced ventilation-perfusion (V/Q) mismatch following endobronchial valve insertion demonstrated by gallium-68 V/Q photon emission tomography/computed tomography. Respirol Case Rep. 2017;5(5):e00253. https://doi.org/10.1002/rcr2.253.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Le Roux PY, Leong TL, Barnett SA, Hicks RJ, Callahan J, Eu P, et al. Gallium-68 perfusion positron emission tomography/computed tomography to assess pulmonary function in lung cancer patients undergoing surgery. Cancer Imaging. 2016;16(1):24. https://doi.org/10.1186/s40644-016-0081-5.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Callahan J, Hofman MS, Siva S, Kron T, Schneider ME, Binns D, et al. High-resolution imaging of pulmonary ventilation and perfusion with 68Ga-VQ respiratory gated (4-D) PET/CT. Eur J Nucl Med Mol Imaging. 2014;41(2):343–9. https://doi.org/10.1007/s00259-013-2607-4.

    Article  CAS  PubMed  Google Scholar 

  33. Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B. EANM guidelines for ventilation/perfusion scintigraphy: part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging. 2009;36(8):1356–70. https://doi.org/10.1007/s00259-009-1170-5.

    Article  CAS  PubMed  Google Scholar 

  34. Le Roux PY, Pelletier-Galarneau M, De Laroche R, Hofman MS, Zuckier LS, Roach P, et al. Pulmonary scintigraphy for the diagnosis of acute pulmonary embolism: a survey of current practices in Australia, Canada, and France. J Nucl Med. 2015;56(8):1212–7. https://doi.org/10.2967/jnumed.115.157743.

    Article  PubMed  Google Scholar 

  35. Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165–71.

    Article  PubMed  Google Scholar 

  36. Burge AJ, Freeman KD, Klapper PJ, Haramati LB. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008;63(4):381–6. https://doi.org/10.1016/j.crad.2007.10.004.

    Article  CAS  PubMed  Google Scholar 

  37. Ghanima W, Nielssen BE, Holmen LO, Witwit A, Al-Ashtari A, Sandset PM. Multidetector computed tomography (MDCT) in the diagnosis of pulmonary embolism: interobserver agreement among radiologists with varied levels of experience. Acta Radiol. 2007;48(2):165–70. https://doi.org/10.1080/02841850601100859.

    Article  CAS  PubMed  Google Scholar 

  38. Di Nisio M, Lee AY, Carrier M, Liebman HA, Khorana AA, Subcommittee on Haemostasis and Malignancy. Diagnosis and treatment of incidental venous thromboembolism in cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2015;13(5):880–3. https://doi.org/10.1111/jth.12883.

    Article  PubMed  Google Scholar 

  39. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033–80. https://doi.org/10.1093/eurheartj/ehu283.

    Article  CAS  PubMed  Google Scholar 

  40. Perrier A, Desmarais S, Miron MJ, de Moerloose P, Lepage R, Slosman D, et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet. 1999;353(9148):190–5. https://doi.org/10.1016/S0140-6736(98)05248-9.

    Article  CAS  PubMed  Google Scholar 

  41. Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med. 1998;129(12):997–1005.

    Article  CAS  PubMed  Google Scholar 

  42. Leblanc M, Leveillee F, Turcotte E. Prospective evaluation of the negative predictive value of V/Q SPECT using 99mTc-Technegas. Nucl Med Commun. 2007;28(8):667–72. https://doi.org/10.1097/MNM.0b013e32827a8e99.

    Article  PubMed  Google Scholar 

  43. Truffault B, Robin P, Tromeur C, Le Duc Pennec A, Abgral R, Bourhis D, et al. Time trend analysis of pulmonary embolism diagnosis with single-photon emission computed tomography ventilation/perfusion imaging. Nucl Med Commun. 2019. https://doi.org/10.1097/MNM.0000000000000990.

  44. Hofman MS, Hicks RJ, Maurer T, Eiber M. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics. 2018;38(1):200–17. https://doi.org/10.1148/rg.2018170108.

    Article  PubMed  Google Scholar 

  45. Sorensen HT, Mellemkjaer L, Steffensen FH, Olsen JH, Nielsen GL. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med. 1998;338(17):1169–73. https://doi.org/10.1056/NEJM199804233381701.

    Article  CAS  PubMed  Google Scholar 

  46. Le Gal G, Le Roux PY. How to assess quality of primary research studies in the medical literature? Semin Nucl Med. 2019;49(2):115–20. https://doi.org/10.1053/j.semnuclmed.2018.11.007.

    Article  PubMed  Google Scholar 

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Acknowledgments

We acknowledge the doctors, radiopharmacists, technologists, nurses and medical physicists at the Peter MacCallum Cancer Team who enabled this research to occur.

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Authors and Affiliations

  1. Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia

    Pierre-Yves Le Roux, Amir Iravani, Jason Callahan, Peter Eu, Eddie Lau, Beverly Woon, Rodney J. Hicks & Michael S. Hofman

  2. Nuclear Medicine, Brest University Hospital, EA3878 (GETBO) IFR 148, Brest, France

    Pierre-Yves Le Roux & Pierre-Yves Salaun

  3. Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

    Kate Burbury

  4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

    Kate Burbury, Rodney J. Hicks & Michael S. Hofman

  5. Respiratory Medicine, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia

    Daniel P. Steinfort

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  1. Pierre-Yves Le Roux
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Correspondence to Pierre-Yves Le Roux or Michael S. Hofman.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol was approved by the Ethics Committee of our institution (14/117). The study was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12614001170617).

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Le Roux, PY., Iravani, A., Callahan, J. et al. Independent and incremental value of ventilation/perfusion PET/CT and CT pulmonary angiography for pulmonary embolism diagnosis: results of the PECAN pilot study. Eur J Nucl Med Mol Imaging 46, 1596–1604 (2019). https://doi.org/10.1007/s00259-019-04338-z

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