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