Clinical identification of malignant pleural effusions

Jianlong Jia; Antonia Marazioti; Apostolos Voulgaridis; Ioannis Psallidas; Anne-Sophie Lamort; Marianthi Iliopoulou; Anthi C Krontira; Ioannis Lilis; Rachelle Asciak; Nikolaos I Kanellakis; Najib M Rahman; Kyriakos Karkoulias; Konstantinos Spiropoulos; Ruonan Liu; Jan-Christian Kaiser; Georgios T Stathopoulos

doi:10.1016/j.tranon.2023.101800

Clinical identification of malignant pleural effusions

Transl Oncol. 2024 Jan:39:101800. doi: 10.1016/j.tranon.2023.101800. Epub 2023 Oct 13.

Authors

Jianlong Jia¹, Antonia Marazioti², Apostolos Voulgaridis³, Ioannis Psallidas⁴, Anne-Sophie Lamort¹, Marianthi Iliopoulou², Anthi C Krontira², Ioannis Lilis², Rachelle Asciak⁵, Nikolaos I Kanellakis⁶, Najib M Rahman⁵, Kyriakos Karkoulias³, Konstantinos Spiropoulos³, Ruonan Liu⁷, Jan-Christian Kaiser⁸, Georgios T Stathopoulos⁹

Affiliations

¹ Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Germany and Ludwig-Maximilian-University (LMU), Munich, Bavaria 81377, Germany; German Center for Lung Research (DZL), Gießen, Hesse 35392, Germany.
² Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece.
³ Department of Pulmonary Medicine, Rio University Hospital, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece.
⁴ Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece; Lungs for Living Research Centre, UCL Respiratory, University College London, London WC1E 6BT, United Kingdom; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, United Kingdom.
⁵ Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, United Kingdom.
⁶ Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, United Kingdom.
⁷ Institute of Infection and Immunity, College of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an China.
⁸ Institute of Radiation Medicine, Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Neuherberg, Bavaria 85764, Germany.
⁹ Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Germany and Ludwig-Maximilian-University (LMU), Munich, Bavaria 81377, Germany; German Center for Lung Research (DZL), Gießen, Hesse 35392, Germany; Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia 26504, Greece. Electronic address: gttstathopoulos@yahoo.gr.

Abstract

Introduction: Pleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.

Methods: A consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n = 238).

Results: Five variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count 〈 2,500/mm³, effusion protein 〉 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (P < 10^-15) in the derivation cohort. The integrated discrimination improvement of MAPED scores showed an increase compared to cytology (p <0.001). Decision curve analysis indicated that the MAPED score generated net clinical benefit. In the validation dataset, the AUC of MAPED scores was 0.723 ( P = 3 × 10^-9) for the MAPED score. Interestingly, MAPED correctly identified 33/42(79%) of cytology-negative patients that indeed had cancer.

Conclusions: The MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures.

Condensed abstract: Diagnostic markers for malignant pleural effusions remain uncertain. The MAPED score identifies malignant pleural effusions and complements cytology and confers no additional risk to the patient or cost to the healthcare system.

Keywords: Aging and cancer; Lactate dehydrogenase; Malignant pleural effusion size; Neutrophil; Protein.