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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

Flow diagram illustrating patient disposition in the test cohort and the validation cohort. Abbreviation: DDU=Drug Development Unit, Royal Marsden Hospital, UK.
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fig1: Flow diagram illustrating patient disposition in the test cohort and the validation cohort. Abbreviation: DDU=Drug Development Unit, Royal Marsden Hospital, UK.

Mentions: Between July 2004 and February 2014, 4172 patients were considered for phase 1 trial at the Drug Development Unit. Of these, 1308 patients were reviewed for the test cohort, with 300 patients treated in a phase 1 trial (Figure 1). Of these patients, 15% had breast cancer, 13% had colorectal cancer, 13% had ovarian cancer, 13% had non-small cell lung cancer, 14% had prostate cancer and 31% had other tumour types. The performance status was ECOG 0 in 35%, and ECOG 1–2 in 65%. The RMH score was 0–1 in 66% and 2–3 in 34% of patients. The median age was 60 years (interquartile range (IQR) 48–67), and 47% were male. The median absolute neutrophil count was 4.24 × 109 l−1 (IQR 3.06–5.68), and the median absolute lymphocyte count was 1.39 × 109 l−1 (IQR 1.02–1.82). The median NLR was 3.08 (IQR 2.06–4.49; Table 1). Stratification for these parameters for the five main tumour types in the test cohort is summarised in Table 1. The median OS was 8.6 months (95% CI 7.4–10.1), with an event rate of 66% and a median follow-up of 6.9 months.


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)

Flow diagram illustrating patient disposition in the test cohort and the validation cohort. Abbreviation: DDU=Drug Development Unit, Royal Marsden Hospital, UK.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Flow diagram illustrating patient disposition in the test cohort and the validation cohort. Abbreviation: DDU=Drug Development Unit, Royal Marsden Hospital, UK.
Mentions: Between July 2004 and February 2014, 4172 patients were considered for phase 1 trial at the Drug Development Unit. Of these, 1308 patients were reviewed for the test cohort, with 300 patients treated in a phase 1 trial (Figure 1). Of these patients, 15% had breast cancer, 13% had colorectal cancer, 13% had ovarian cancer, 13% had non-small cell lung cancer, 14% had prostate cancer and 31% had other tumour types. The performance status was ECOG 0 in 35%, and ECOG 1–2 in 65%. The RMH score was 0–1 in 66% and 2–3 in 34% of patients. The median age was 60 years (interquartile range (IQR) 48–67), and 47% were male. The median absolute neutrophil count was 4.24 × 109 l−1 (IQR 3.06–5.68), and the median absolute lymphocyte count was 1.39 × 109 l−1 (IQR 1.02–1.82). The median NLR was 3.08 (IQR 2.06–4.49; Table 1). Stratification for these parameters for the five main tumour types in the test cohort is summarised in Table 1. The median OS was 8.6 months (95% CI 7.4–10.1), with an event rate of 66% and a median follow-up of 6.9 months.

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