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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

Receiver operator characteristic curve analysis for the test and validation cohorts. The receiver operator characteristic curve analysis for the (A) test and (B) validation cohorts shows the ability of the different models to discriminate for overall survival. The models tested in addition to the RMH score alone and the NLR alone were RMH score+NLR50 and RMH score+Log10NLR, as they were found to be significantly associated with overall survival in multivariate analysis. Abbreviations: NLR=Neutrophil–lymphocyte ratio; RMH=Royal Marsden Hospital Score.
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fig3: Receiver operator characteristic curve analysis for the test and validation cohorts. The receiver operator characteristic curve analysis for the (A) test and (B) validation cohorts shows the ability of the different models to discriminate for overall survival. The models tested in addition to the RMH score alone and the NLR alone were RMH score+NLR50 and RMH score+Log10NLR, as they were found to be significantly associated with overall survival in multivariate analysis. Abbreviations: NLR=Neutrophil–lymphocyte ratio; RMH=Royal Marsden Hospital Score.

Mentions: ROC curve analysis assessed the ability of the NLR to discriminate for OS compared with the RMH score and to evaluate any improvement of its discriminative ability by adding an NLR-measure. The RMH score+Log10NLR and RMH score+NLR50 were evaluated here (Figure 3A and Table 3A). The C-index for the RMH score alone was 0.63 (95% CI 0.56–0.70; P=0.0002) and for the Log10NLR alone was 0.58 (95% CI 0.52–0.65; P=0.02), with no difference in the discriminating ability between them (P=0.9). Both models tested were significant in discriminating for OS. Comparing these to the RMH score alone showed that RMH score+Log10NLR (P=0.005) significantly improved the discriminative ability of the model; however, the RMH score+NLR50 did not (P=0.006; Table 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)

Receiver operator characteristic curve analysis for the test and validation cohorts. The receiver operator characteristic curve analysis for the (A) test and (B) validation cohorts shows the ability of the different models to discriminate for overall survival. The models tested in addition to the RMH score alone and the NLR alone were RMH score+NLR50 and RMH score+Log10NLR, as they were found to be significantly associated with overall survival in multivariate analysis. Abbreviations: NLR=Neutrophil–lymphocyte ratio; RMH=Royal Marsden Hospital Score.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Receiver operator characteristic curve analysis for the test and validation cohorts. The receiver operator characteristic curve analysis for the (A) test and (B) validation cohorts shows the ability of the different models to discriminate for overall survival. The models tested in addition to the RMH score alone and the NLR alone were RMH score+NLR50 and RMH score+Log10NLR, as they were found to be significantly associated with overall survival in multivariate analysis. Abbreviations: NLR=Neutrophil–lymphocyte ratio; RMH=Royal Marsden Hospital Score.
Mentions: ROC curve analysis assessed the ability of the NLR to discriminate for OS compared with the RMH score and to evaluate any improvement of its discriminative ability by adding an NLR-measure. The RMH score+Log10NLR and RMH score+NLR50 were evaluated here (Figure 3A and Table 3A). The C-index for the RMH score alone was 0.63 (95% CI 0.56–0.70; P=0.0002) and for the Log10NLR alone was 0.58 (95% CI 0.52–0.65; P=0.02), with no difference in the discriminating ability between them (P=0.9). Both models tested were significant in discriminating for OS. Comparing these to the RMH score alone showed that RMH score+Log10NLR (P=0.005) significantly improved the discriminative ability of the model; however, the RMH score+NLR50 did not (P=0.006; Table 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