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Peer-reviewedCC BY 4.0Cancers

Development of the OncoScore: A Diagnostic Prediction Score for Previously Unrecognized Malignancy in Patients with Acute Pulmonary Embolism

  • Aleksandra Kozic1
  • Sonja Salinger2,3
  • Boris Dzudovic1,4
  • Jovan Matijasevic5,6
  • Marija Benic5
  • Vladimir Miloradovic7,8
  • Ema Jevtic7
  • Tamara Kovacevic Preradovic9,10
  • Ljiljana Kos9,10
  • Bjanka Bozovic11
  • Irena Mitevska12,13
  • Marijan Bosevski12,13
5 more authors
  • Ana Kovacevic-Kuzmanovic14
  • Aleksandar Neskovic15,16
  • Bojan Mitrovic15,16
  • Srdjan Kafedzic15
  • Slobodan Obradovic1,17
17 affiliations
  1. 1Medical Faculty of the Military Medical Academy, University of Defence, 17 Crnotravska, 11000 Belgrade, Serbia
  2. 2Clinic of Cardiology, University Clinical Center Nis, 18000 Nis, Serbia
  3. 3Faculty of Medicine, University of Nis, 18000 Nis, Serbia
  4. 4Clinic for Emergency Internal Medicine, Military Medical Academy, 11000 Belgrade, Serbia
  5. 5Clinic for Intensive Care Medicine and Pulmonary Vascular Diseases, Institute for Pulmonary Diseases Vojvodina, 21204 Sremska Kamenica, Serbia
  6. 6Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
  7. 7Clinic of Cardiology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia
  8. 8Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
  9. 9Clinic of Cardiology, University Clinical Center of the Republic of Srpska, 78000 Banja Luka, Republic of Srpska, Bosnia and Herzegovina
  10. 10Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Republic of Srpska, Bosnia and Herzegovina
  11. 11Clinic of Cardiology, Clinical Center of Montenegro, 81000 Podgorica, Montenegro
  12. 12University Clinic for Cardiology and Cardiovascular Surgery, National Center for Cardiovascular Diseases, 1000 Skopje, North Macedonia
  13. 13Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, North Macedonia
  14. 14Department for Internal Medicine, General Hospital Pancevo, 26000 Pancevo, Serbia
  15. 15Department of Cardiology, Clinical Hospital Center Zemun, 11080 Belgrade, Serbia
  16. 16Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
  17. 17Clinic for Cardiology, Military Medical Academy, 11000 Belgrade, Serbia
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Abstract

Background/Objectives: Pulmonary embolism (PE) may represent the first clinical manifestation of a previously unrecognized malignancy. We aimed to develop the OncoScore, a diagnostic prediction score for estimating the probability of previously unrecognized malignancy being diagnosed during the index hospitalization for acute PE. Methods: We conducted a retrospective diagnostic prediction model derivation study using prospectively collected data from the multicenter Regional Pulmonary Embolism Registry (REPER). Candidate predictors were assessed using logistic regression and Chi-square Automatic Interaction Detection (CHAID) analysis, and independent predictors were incorporated into the OncoScore. Discrimination was assessed by receiver operating characteristic (ROC) analysis, calibration by calibration slope and a calibration plot, and internal validation by bootstrap resampling. Diagnostic performance measures were calculated using the cut-off value determined by the Youden index. Results: Among 2615 patients with acute PE, 91 had newly diagnosed malignancy, 265 had previously known malignancy, and 2259 had no malignancy. The final OncoScore included hemoglobin, C-reactive protein, platelet count, and leukocyte count, with a total score ranging from 0 to 7 points. The OncoScore yielded an area under the curve (AUC) of 0.702 (95% confidence interval [CI] 0.653–0.751; p < 0.001). Bootstrap internal validation of the fixed score yielded an optimism-corrected AUC of 0.7013 and an optimism-corrected calibration slope of 1.015. When predictor selection and CHAID cut-point determination were repeated within the bootstrap procedure, the optimism-corrected AUC was 0.6560. Patients were stratified as low (≤2), intermediate (3–4), and high risk (≥5), with observed malignancy prevalences of 1.1%, 5.5%, and 10.8%, respectively. At a cut-off of ≥3 points, sensitivity was 87.5%, specificity 46.5%, positive predictive value 6.4%, and negative predictive value 98.9%. Conclusions: The OncoScore is a simple laboratory-based prediction tool that showed moderate discrimination and identified clinically distinct risk strata for malignancy diagnosed during the index hospitalization for acute PE. The score should be considered a preliminary derivation-stage model, and independent external validation is required before clinical implementation.

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Cite

BibTeXRIS
BibTeX
@article{kozic2026development,
  title = {{Development of the OncoScore: A Diagnostic Prediction Score for Previously Unrecognized Malignancy in Patients with Acute Pulmonary Embolism}},
  author = {Aleksandra Kozic and Sonja Salinger and Boris Dzudovic and Jovan Matijasevic and Marija Benic and Vladimir Miloradovic and Ema Jevtic and Tamara Kovacevic Preradovic and Ljiljana Kos and Bjanka Bozovic and Irena Mitevska and Marijan Bosevski and Ana Kovacevic-Kuzmanovic and Aleksandar Neskovic and Bojan Mitrovic and Srdjan Kafedzic and Slobodan Obradovic},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18213440},
  url = {https://www.mdpi.com/2072-6694/18/21/3440},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Development of the OncoScore: A Diagnostic Prediction Score for Previously Unrecognized Malignancy in Patients with Acute Pulmonary Embolism
AU  - Aleksandra Kozic
AU  - Sonja Salinger
AU  - Boris Dzudovic
AU  - Jovan Matijasevic
AU  - Marija Benic
AU  - Vladimir Miloradovic
AU  - Ema Jevtic
AU  - Tamara Kovacevic Preradovic
AU  - Ljiljana Kos
AU  - Bjanka Bozovic
AU  - Irena Mitevska
AU  - Marijan Bosevski
AU  - Ana Kovacevic-Kuzmanovic
AU  - Aleksandar Neskovic
AU  - Bojan Mitrovic
AU  - Srdjan Kafedzic
AU  - Slobodan Obradovic
PY  - 2026
DA  - 2026/10/24
JO  - Cancers
DO  - 10.3390/cancers18213440
UR  - https://www.mdpi.com/2072-6694/18/21/3440
AB  - Background/Objectives: Pulmonary embolism (PE) may represent the first clinical manifestation of a previously unrecognized malignancy. We aimed to develop the OncoScore, a diagnostic prediction score for estimating the probability of previously unrecognized malignancy being diagnosed during the index hospitalization for acute PE. Methods: We conducted a retrospective diagnostic prediction model derivation study using prospectively collected data from the multicenter Regional Pulmonary Embolism Registry (REPER). Candidate predictors were assessed using logistic regression and Chi-square Automatic Interaction Detection (CHAID) analysis, and independent predictors were incorporated into the OncoScore. Discrimination was assessed by receiver operating characteristic (ROC) analysis, calibration by calibration slope and a calibration plot, and internal validation by bootstrap resampling. Diagnostic performance measures were calculated using the cut-off value determined by the Youden index. Results: Among 2615 patients with acute PE, 91 had newly diagnosed malignancy, 265 had previously known malignancy, and 2259 had no malignancy. The final OncoScore included hemoglobin, C-reactive protein, platelet count, and leukocyte count, with a total score ranging from 0 to 7 points. The OncoScore yielded an area under the curve (AUC) of 0.702 (95% confidence interval [CI] 0.653–0.751; p < 0.001). Bootstrap internal validation of the fixed score yielded an optimism-corrected AUC of 0.7013 and an optimism-corrected calibration slope of 1.015. When predictor selection and CHAID cut-point determination were repeated within the bootstrap procedure, the optimism-corrected AUC was 0.6560. Patients were stratified as low (≤2), intermediate (3–4), and high risk (≥5), with observed malignancy prevalences of 1.1%, 5.5%, and 10.8%, respectively. At a cut-off of ≥3 points, sensitivity was 87.5%, specificity 46.5%, positive predictive value 6.4%, and negative predictive value 98.9%. Conclusions: The OncoScore is a simple laboratory-based prediction tool that showed moderate discrimination and identified clinically distinct risk strata for malignancy diagnosed during the index hospitalization for acute PE. The score should be considered a preliminary derivation-stage model, and independent external validation is required before clinical implementation.
SN  - 2072-6694
ER  -