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

• Verfasst von: Diefenhardt, Markus [VerfasserIn]
• Verfasst von: Hofheinz, Ralf-Dieter [VerfasserIn]
• Titel: Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial
• Verf.angabe: Markus Diefenhardt, Ralf-Dieter Hofheinz, Daniel Martin, Tim Beißbarth, Dirk Arnold, Arndt Hartmann, Jens von der Grün, Robert Grützmann, Torsten Liersch, Philipp Ströbel, Gerhard G. Grabenbauer, Michael Rieger, Rainer Fietkau, Ullrich Graeven, Jürgen Weitz, Gunar Folprecht, Michael Ghadimi, Franz Rödel, Claus Rödel, Emmanouil Fokas
• E-Jahr: 2019
• Jahr: 14 March 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 22.10.2019
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2019
• Band/Heft Quelle: 145(2019), 8, Seite 2282-2291
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.32274
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: clinical radiotherapeutic studies
• Sach-SW: clinical trials
• Sach-SW: colorectal cancer
• Sach-SW: molecular markers of metastasis and progression
• Sach-SW: radiochemotherapy
• K10plus-PPN: 1679313541

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.