Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial

Diefenhardt M, Hofheinz RD, Martin D, Beißbarth T, Arnold D, Hartmann A, von der Grün J, Grützmann R, Liersch T, Ströbel P, Grabenbauer GG, Rieger M, Fietkau R, Graeven U, Weitz J, Folprecht G, Ghadimi M, Rödel F, Rödel C, Fokas E (2019)

Publication Type: Journal article

Publication year: 2019

Journal

International Journal of Cancer Wiley-Blackwell

DOI: 10.1002/ijc.32274

Abstract

Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5-FU-based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO-04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow-up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease-free survival (DFS; HR 1.457; 95% CI 1.163–1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266–2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264–2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment-induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5-FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high-level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies.

Authors with CRIS profile

Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie Rainer Fietkau Lehrstuhl für Strahlentherapie

Involved external institutions

Frankfurt Cancer Institute DE Germany (DE) Universität Mannheim DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) Asklepios Klinik Altona DE Germany (DE) Klinikum Coburg DE Germany (DE) Kliniken Maria Hilf GmbH DE Germany (DE) Southern Medical University / 南方医科大学 CN China (CN)

How to cite

APA:

Diefenhardt, M., Hofheinz, R.D., Martin, D., Beißbarth, T., Arnold, D., Hartmann, A.,... Fokas, E. (2019). Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial. International Journal of Cancer. https://doi.org/10.1002/ijc.32274

MLA:

Diefenhardt, Markus, et al. "Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial." International Journal of Cancer (2019).

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