Elsevier

Digestive and Liver Disease

Volume 46, Issue 9, September 2014, Pages 846-853
Digestive and Liver Disease

Oncology
Prognostic value of neutrophil-to-lymphocyte ratio in patients treated with concurrent chemoradiotherapy for locally advanced oesophageal cancer

https://doi.org/10.1016/j.dld.2014.05.009Get rights and content

Abstract

Background

We performed a retrospective analysis of Asian patients with locally advanced oesophageal cancer to test the hypothesis that an elevated neutrophil-to-lymphocyte ratio is associated with a poor survival rate after definitive concurrent chemoradiotherapy.

Methods

In total, 138 patients diagnosed with locally advanced oesophageal cancer (TNM classification of malignant tumours stage II or III) who were treated with definitive concurrent chemoradiotherapy between January 2005 and December 2010 were retrospectively analysed. Definitive concurrent chemoradiotherapy was performed using two different chemotherapy regimens.

Results

The median follow-up duration was 39.5 months (range 1.1–93.4). The median progression-free survival was 14.0 months, and the median overall survival was 19.9 months. Compared with the low (<2.0) neutrophil-to-lymphocyte ratio group (n = 43, 31.2%), the high (≥2.0) neutrophil-to-lymphocyte ratio group (n = 95, 68.8%) exhibited significant decreases in the durations of both progression-free survival and overall survival. Using multivariate analysis, an elevated neutrophil-to-lymphocyte ratio was also significantly associated with decreased progression-free survival (HR 1.799; 95% CI, 1.050–3.083; P = 0.032) and overall survival duration (HR 2.115; 95% CI, 1.193–3.749; P = 0.010).

Conclusions

The pretreatment neutrophil-to-lymphocyte ratio is a useful prognostic marker in patients with locally advanced oesophageal cancer treated with definitive concurrent chemoradiotherapy.

Introduction

Surgical resection is considered a curative aim for early stage oesophageal cancer (EC). However, over 60% of cases exhibit unresectable disease at presentation [1]. For these patients, definitive concurrent chemoradiotherapy (CCRT) has been suggested as an option for both prolonging survival and relieving symptoms. In randomised trials, the addition of cisplatin-based chemotherapy to radiotherapy (RT) significantly improves survival over RT alone [2], [3], [4]. Despite the relatively prolonged median and overall survival times conferred by CCRT, marked heterogeneity still exists between the survival duration of patients with locally advanced EC [5], [6], [7]. Thus, prognostic factors have been sought that will enable more precise patient stratification and improve decision-making by clinicians. Demographic factors such as weight loss or performance status have been suggested to be related to treatment response and survival in previous studies of inoperable oesophago-gastric cancer [8], [9]. However, the use of these demographic factors as prognostic touchstones remains problematic, since they are often not accurately defined and are subject to bias. Both tumour- and treatment-related factors such as tumour length, T-stage, N-stage, histopathological grade, radiotherapy dose, and CCRT have been reported to be associated with disease progression and survival [10]. However, data are still lacking regarding prognostic factors associated with overall survival duration or treatment response for Asian EC patients treated with definitive CCRT.

Recently, various studies have proposed measurements and/or scoring systems to simplify and standardise the measurement of systemic inflammatory response in clinical practice [11], [12]. These parameters include the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the modified Glasgow Prognostic Score (mGPS) in gastrointestinal tract cancer. For example, the NLR represents a non-specific measurement of systemic inflammation; furthermore, an elevated NLR has been shown to be associated with poor prognosis in patients with cardiovascular disease, colorectal cancer, renal cell carcinoma, ovarian cancer, and EC [13], [14]. It has been reported as part of the systemic inflammatory response, associated with compromised immune function and host anti-tumour immune responses regardless of ethnicity [15]. However, with regard to EC, the NLR has only been investigated in pre-operative or neoadjuvant settings, and its predictive abilities have not been assessed in locally advanced cases, indicated for definitive CCRT [16], [17], [18], [19].

We therefore performed a retrospective analysis of data from Asian patients with locally advanced EC. Our primary hypothesis was that elevated pre-CCRT NLRs are associated with poor survival results or treatment responses after definitive CCRT. We also assessed the appropriate cut-off value for defining an elevated NLR, and examined the value of other factors for predicting survival outcomes associated with definitive CCRT.

Section snippets

Patient eligibility

Eligible cases consisted of 903 patients diagnosed with EC at Severance Hospital, Yonsei University College of Medicine (Seoul, Korea) between January 2005 and December 2010. Among them, patients meeting one or more of the following exclusion criteria were omitted from further study: (1) any malignancy except EC during the study period; (2) previous surgery, with either a curative or a palliative aim; (3) previous radiotherapy or chemotherapy only; (4) previous palliative or supportive care

Radiotherapy

Radiotherapy was performed once daily, 5 times a week, except for weekends and public holidays. Daily doses of 1.8 Gy were administered. Linac accelerators, with 10–15 MeV photons and a multiple field technique, were used for treatment. Portal images were obtained at least once a week. The total dose administered to planning target volume (PTV)-2 and PTV-1 patients was 50.4 and 63 Gy. Dose heterogeneities within the target volume were less than 5%.

Target volume definition

PTV-1 included the primary tumour volume and the

Patient baseline characteristics based on pre-CCRT NLR

A total of 138 locally advanced EC patients underwent definitive CCRT during the study period. The median duration of follow-up was 39.5 months (range 1.1–93.4). The baseline characteristics of patients at enrolment are summarised in Table 1 and Supplementary Table 1. Most patients were male (91.7%), and the mean age was 67.6 ± 7.7 years. Performance statuses of most patients were classified as ECOG grade 0–1 (97.8%), and the mean Charlson's comorbidity index was 5.9. Most patients exhibited

Discussion

In the present study, we analysed data from a cohort of patients with locally advanced EC to evaluate whether the NLR is a predictor of disease progression, overall mortality, or clinical response after CCRT. We found that an elevated pre-CCRT NLR was associated with a nearly 2-fold increased risk of progression and death, independent of patient, tumour, and therapeutic characteristics associated with poor outcomes. To the best of our knowledge, this is the first study to assess the value of

Conflict of interest

None declared.

Acknowledgements

The authors are grateful to Dong-Su Jang (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the figures.

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