Added diagnostic value of routinely measured hematology variables in diagnosing immune checkpoint inhibitor mediated toxicity in the emergency department
Niemantsverdriet, Michael S A; Vrijsen, Bram E L; Visser 't Hooft, Therese; Suijkerbuijk, Karijn P M; van Solinge, Wouter W; Ten Berg, Maarten J; Haitjema, Saskia
(2023) Cancer Medicine, volume 12, issue 11, pp. 12462 - 12469
(Article)
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICI) show remarkable results in cancer treatment, but at the cost of immune-related adverse events (irAE). irAE can be difficult to differentiate from infections or tumor progression, thereby challenging treatment, especially in the emergency department (ED) where time and clinical information are limited. As infections are
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traceable in blood, we were interested in the added diagnostic value of routinely measured hematological blood cell characteristics in addition to standard diagnostic practice in the ED to aid irAE assessment. METHODS: Hematological variables routinely measured with our hematological analyzer (Abbott CELL-DYN Sapphire) were retrieved from Utrecht Patient Oriented Database (UPOD) for all patients treated with ICI who visited the ED between 2013 and 2020. To assess the added diagnostic value, we developed and compared two models; a base logistic regression model trained on the preliminary diagnosis at the ED, sex, and gender, and an extended model trained with lasso that also assessed the hematology variables. RESULTS: A total of 413 ED visits were used in this analysis. The extended model showed an improvement in performance (area under the receiver operator characteristic curve) over the base model, 0.79 (95% CI 0.75-0.84), and 0.67 (95% CI 0.60-0.73), respectively. Two standard blood count variables (eosinophil granulocyte count and red blood cell count) and two advanced variables (coefficient of variance of neutrophil depolarization and red blood cell distribution width) were associated with irAE. CONCLUSION: Hematological variables are a valuable and inexpensive aid for irAE diagnosis in the ED. Further exploration of the predictive hematological variables could yield new insights into the pathophysiology underlying irAE and in distinguishing irAE from other inflammatory conditions.
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Keywords: biomarkers, emergency department, immune checkpoint inhibitor, immune-related adverse events, machine learning, Oncology, Radiology Nuclear Medicine and imaging, Cancer Research, Journal Article
ISSN: 2045-7634
Publisher: John Wiley and Sons Ltd
Note: Funding Information: MN is employed by SkylineDx, Rotterdam and receives a PhD fellowship from SkylineDx, Rotterdam. KS: Consulting/advisory relationship: Bristol Myers Squibb, Merck Sharp and Dome, Abbvie, Pierre Fabre, Novartis. Honoraria received: Novartis, Roche, Merck Sharp and Dome. Research funding, TigaTx, Bristol Myers Squibb, Philips, unrelated to this project. All paid to institution and outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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