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The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials.

Kumar R, Geuna E, Michalarea V, Guardascione M, Naumann U, Lorente D, Kaye SB, de Bono JS - Br. J. Cancer (2015)

Bottom Line: Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS.In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use.This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.

ABSTRACT

Background: Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.

Methods: This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.

Results: The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

Conclusions: NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.

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Related in: MedlinePlus

Overall survival (OS) analysis for the NLR quartiles, using Kaplan–Meier product-limit estimates method. The differences in OS were tested using the log-rank test. OS was analysed for the (A) test cohort and (B) validation cohort with the data stratified into the first, second, third and fourth quartiles. Both analyses show lower quartiles having a better survival when compared with the higher quartiles, with a statistically significant for trend. The ‘RMH score+NLR50' model for OS (C) with the discrete scores of 0, 1, 2, 3 and 4 and (D) with the clustering of scores 0–1 and 2–4, all for the validation cohort. Abbreviations: NLR=neutrophil–lymphocyte ratio; OS=overall survival.
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fig2: Overall survival (OS) analysis for the NLR quartiles, using Kaplan–Meier product-limit estimates method. The differences in OS were tested using the log-rank test. OS was analysed for the (A) test cohort and (B) validation cohort with the data stratified into the first, second, third and fourth quartiles. Both analyses show lower quartiles having a better survival when compared with the higher quartiles, with a statistically significant for trend. The ‘RMH score+NLR50' model for OS (C) with the discrete scores of 0, 1, 2, 3 and 4 and (D) with the clustering of scores 0–1 and 2–4, all for the validation cohort. Abbreviations: NLR=neutrophil–lymphocyte ratio; OS=overall survival.

Mentions: To determine the prognostic value of the NLR, OS was assessed in each of the NLR quartiles, with quartile-1 being used as a reference group. The median OS was 10.5 months (95% CI 8.9–23.5) for quartile-1, 10.3 months (95% CI 7.0–14.7) for quartile-2 (HR=1.04, P=0.8), 7.9 months (95% CI 4.8–11.6) for quartile-3 (HR=1.56, P=0.03) and 6.5 months (95% CI 5.4–7.6) for quartile-4 (HR=2.08, P=0.001; P-value for trend P<0.0001; Figure 2A).


The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials.

Kumar R, Geuna E, Michalarea V, Guardascione M, Naumann U, Lorente D, Kaye SB, de Bono JS - Br. J. Cancer (2015)

Overall survival (OS) analysis for the NLR quartiles, using Kaplan–Meier product-limit estimates method. The differences in OS were tested using the log-rank test. OS was analysed for the (A) test cohort and (B) validation cohort with the data stratified into the first, second, third and fourth quartiles. Both analyses show lower quartiles having a better survival when compared with the higher quartiles, with a statistically significant for trend. The ‘RMH score+NLR50' model for OS (C) with the discrete scores of 0, 1, 2, 3 and 4 and (D) with the clustering of scores 0–1 and 2–4, all for the validation cohort. Abbreviations: NLR=neutrophil–lymphocyte ratio; OS=overall survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385959&req=5

fig2: Overall survival (OS) analysis for the NLR quartiles, using Kaplan–Meier product-limit estimates method. The differences in OS were tested using the log-rank test. OS was analysed for the (A) test cohort and (B) validation cohort with the data stratified into the first, second, third and fourth quartiles. Both analyses show lower quartiles having a better survival when compared with the higher quartiles, with a statistically significant for trend. The ‘RMH score+NLR50' model for OS (C) with the discrete scores of 0, 1, 2, 3 and 4 and (D) with the clustering of scores 0–1 and 2–4, all for the validation cohort. Abbreviations: NLR=neutrophil–lymphocyte ratio; OS=overall survival.
Mentions: To determine the prognostic value of the NLR, OS was assessed in each of the NLR quartiles, with quartile-1 being used as a reference group. The median OS was 10.5 months (95% CI 8.9–23.5) for quartile-1, 10.3 months (95% CI 7.0–14.7) for quartile-2 (HR=1.04, P=0.8), 7.9 months (95% CI 4.8–11.6) for quartile-3 (HR=1.56, P=0.03) and 6.5 months (95% CI 5.4–7.6) for quartile-4 (HR=2.08, P=0.001; P-value for trend P<0.0001; Figure 2A).

Bottom Line: Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS.In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use.This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.

ABSTRACT

Background: Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.

Methods: This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.

Results: The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

Conclusions: NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.

Show MeSH
Related in: MedlinePlus