Is the derived neutrophil to lymphocyte ratio (dNLR) an independent prognostic marker in patients with metastatic colorectal cancer (mCRC)? Analysis of the CO.17 and CO.20 studies

3598 Background: High blood neutrophil-to-lymphocyte ratio (NLR) has been previously identified as a poor prognostic marker in patients with metastatic colorectal cancer (mCRC). However, the underlying pathophysiology associated with this marker is not well defined. We validated this biomarker and investigated the relationship between circulating cytokines and high NLR. Methods: NLRs were calculated retrospectively from the ratio of peripheral blood absolute neutrophil and lymphocyte counts, and segregated based on previously determined cutoff of ≤5 and >5. Four cohorts with a total of 805 CRC pts were evaluated to confirm the prognostic clinical significance of NLR. Plasma cytokine levels were evaluated in exploratory (n=39) and validation cohorts (n=166) of previously untreated mCRC patients using multiplex-bead assays, and correlated with NLR. Results: High NLR is present in 20% of CRC patients and is associated with poor prognosis, independent of known prognostic factors (Table). Expression of 6 cytokines (IL-6, IL-8, IL-2Ra, HGF, M-CSF and VEGF) correlated with NLR>5 in both the exploratory and validation cohort. In the validation cohort, an additional 14 cytokines correlated with NLR>5, including high EREG,AREG, and TGF-α, and low TRAIL. By hierarchial clustering, these 20 cytokines fall into 3 overlapping major clusters: angiogenic cytokines, inflammatory cytokines, and epidermal growth factor ligands. In the validation cohort, pts with a composite cytokine score below the median have longer survival than patients with high scores (40.0 mo vs 20.0 mo, HR = 2.24; 95% CI=1.47–3.41; P<0.001). Conclusions: High peripheral blood neutrophil/lymphocyte ratio (NLR) is associated with poor outcomes independent of other known prognostic features. NLR correlates with discrete sets of cytokines which may reflect important biological features in poor prognosis mCRC. [Table: see text]

Download Full-text

Capecitabine monotherapy and the clinical significance of neutrophil-lymphocyte ratio versus platelet-lymphocyte ratio in patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.660 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 660-660 ◽

Cited By ~ 5

Author(s):

Suee Lee ◽

Hyuk-Chan Kwon ◽

Sung-Hyun Kim ◽

Sung Yong Oh ◽

Ji Hyun Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Disease Control ◽

Metastatic Colorectal Cancer ◽

Prognostic Marker ◽

Univariate Analysis ◽

Hazard Ratio ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Platelet Lymphocyte Ratio ◽

Third Line

660 Background: Oxaliplatin- and irinotecan-based combination chemotherapy with infusional 5-FU and leucovorin are currently the standard therapies for metastatic colorectal cancer. The objectives of this study were to evaluate the efficacy of capecitabine monotherapy as third line therapy for metastatic colorectal cancer after failure of chemotherapy containing oxaliplatin and irinotecan, and to determine whether the neutrophil-lymphocyte ratio (NLR), or the platelet-lymphocyte ratio (PLR) are significant prognostic marker in metastatic colorectal cancer. Methods: We analyzed 60 patients with metastatic colorectal cancer who received capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. Capecitabine was administered at 1250mg/m2 twice daily for 2 weeks, every 3 weeks. The NLR and PLR were calculated from complete blood counts in baseline laboratory test before the first cycle chemotherapy. Results: The overall response rate was 6.7% and stable disease was 41.7%. The disease control rate was 48.3%. The median progression-free survival (PFS) was 2.8 months (95% CI, 1.5-4.1 months) and the median overall survival (OS) was 9.7 months (95% CI, 7.6-11.7 months). The most frequent adverse event was hand-foot syndrome (all-grade 26.6%; grade3 5%). The response of capecitabine, NLR, and PLR were observed as good prognostic markers of OS in univariate analysis (p<0.001, 0.004, and 0.002, respectively). The response of capecitabine and PLR were independent prognostic marker in multivariate analysis (Hazard ratio 2.757, 95% CI 1.357-5.599, p=0.005 and hazard ratio 2.091, 95% CI 1.231-3.552, p=0.006, respectively). Conclusions: The capecitabine monotherapy showed a moderate disease control and a tolerable toxicity profile as third line treatment for metastatic colorectal cancer. The response of capecitabine and PLR may be simple and useful prognostic index for metastatic colorectal cancer.

Download Full-text