Dataset Information

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

ABSTRACT:

Background

The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer.

Methods

A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR = ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of ? 2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan-Meier method. Comparison between groups was performed using Cox regression.

Results

A total of 1630 patients were assigned to the continuous (N = 815) or intermittent (N = 815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR = 1.70; 95% CI = 1.52-1.90; P < 0.001). The estimate of the hazard ratio did not alter substantially (HR = 1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count.

Conclusions

Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy.

SUBMITTER: Grenader T

PROVIDER: S-EPMC4800295 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

Grenader Tal T Nash Stephen S Adams Richard R Kaplan Richard R Fisher David D Maughan Tim T Bridgewater John J

British journal of cancer 20160218 6

<h4>Background</h4>The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer.<h4>Methods</h4>A post hoc exploratory analysis of COIN arms A and C was perfo ...[more]

PMID: 26889974

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Project description:ObjectiveNeutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR) have been proposed as prognostic biomarkers in multiple cancers. However, the implications of NLR and PLR in the responsiveness to neoadjuvant chemoradiotherapy (nCRT) remain to be clarified in locally advanced rectal cancer (LARC) patients. This retrospective study investigated the prognostic value of NLR and PLR in nCRT responsiveness of LARC patients.MethodsA total number of 86 patients diagnosed with LARC and treated with nCRT and total mesorectal excision were retrospectively followed from 2013 to 2016. Receiver operating characteristic (ROC) curve was used to determine the cutoff values of NLR and PLR, and the patients were divided into NLR elevation and NLR decrease groups, or PLR elevation and PLR decrease groups. The correlation between NLR and PLR changes, and clinicopathological factors were analyzed. The relationship between NLR and PLR changes and the curative responsiveness towards nCRT were further evaluated.ResultsNLR and PLR changes after nCRT were significantly correlated with the distance of tumors to the anus and BMI (body mass index) (P < 0.05). The clinical remission rate of patients with NLR reduction was 72.09% (31/43), which was significantly higher than that in patients with NLR increment (22/43, 51.16%). There was no significant difference in the clinic remission rate between the patients with PLR reduction and those with PLR increment (P > 0.05). However, the pathological responsiveness rate was significantly higher in patients with PLR reduction (21/43, 48.84%) when compared to the ones with PLR increment (9/43, 20.9%) (P = 0.036).ConclusionOur data indicate that in LARC patients with nCRT, the reduction of NLR and the reduction of PLR could serves as predictors for the clinic remission rate and pathological responsiveness rate, respectively. The combination of NLR and PLR changes may be employed as a simple and effective prognostic parameter to predict the treatment outcome of nCRT in LARC.

Project description:BackgroundWhen cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim.MethodsCOIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1.162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448.Findings1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15.8 months (IQR 9.4-26.1) in arm A and 14.4 months (8.0-24.7) in arm C (hazard ratio [HR] 1.084, 80% CI 1.008-1.165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19.6 months (13.0-28.1) in arm A and 18.0 months (12.1-29.3) in arm C (HR 1.087, 0.986-1.198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400,000 per μL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0.96 (95% CI 0.80-1.15, p=0.66), versus 1.54 (1.17-2.03, p=0.0018) in patients with a raised platelet count (p=0.0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand-foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment.InterpretationAlthough this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break.FundingCancer Research UK.

Dataset Information

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

Background

Methods

Results

Conclusions

Publications

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

Similar Datasets

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