ORIGINAL RESEARCH Does Neutrophil-to-Lymphocyte Ratio (NLR) Predict Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma? Santhosh Anand 1 & Gajendra Bhati 1 & Ramprakash Gurram 1 & Senthil Gnanasekaran 1 & Vikram Kate 2 & Biju Pottakkat 1 & Raja Kalayarasan 1 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Background Neoadjuvant chemoradiotherapy (nCRT), followed by surgery, is the current standard of care for patients with locally advanced esophageal squamous cell carcinoma. However, up to 30% of the patients do not respond to nCRT. Hence, a simple, cost-effective marker to predict response before initiation of nCRT is needed. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic marker in various cancers. However, its role as a predictive marker in patients with esophageal SCC planned for nCRT has not been prospectively analyzed. Materials and Methods All consecutive patients with locally advanced (T1N1 and T2–T4a with or without nodal involvement) SCC planned for nCRT (CROSS protocol) followed by esophagectomy with total two field lymphadenectomy between December 2013 and December 2019 were included in this prospective analytical cohort study. NLR was calculated 1 week before starting the nCRT and was correlated with the histopathological response [Mandard tumor regression grade (TRG)]. Results Of the 216 patients with esophageal cancer evaluated during the study period, 57 patients with SCC who fulfilled the inclusion criteria were included. A good pathologic response (TRG 1 and 2) to nCRT was seen in 28 (49.1%) patients. Using a ROC curve, the optimal cutoff value of pretherapy NLR for predicting good pathologic response was 2.33. With an NLR cutoff value of 2.33, 53.3% of patients had a good pathologic response to nCRT compared with 47.6% patients with NLR ≥ 2.33 (P = 0.77). Conclusion In patients with locally advanced esophageal SCC, NLR is not a useful marker to predict pathologic response to nCRT. Keywords Neutrophil-to-lymphocyte ratio . Esophageal cancer . Neoadjuvant therapy . Squamous cell carcinoma Introduction Multimodality treatment involving neoadjuvant therapy followed by surgery is the preferred approach for locally ad- vanced esophageal cancer to reduce locoregional recurrence and distant metastasis [1]. However, nearly one-third of eligi- ble patients do not respond to neoadjuvant therapy. These subsets of patients have a poor long-term outcome [1, 2]. Predicting response before initiation of neoadjuvant therapy can spare nonresponders from treatment-related toxicity and unnecessary delay in surgery. While multiple predictive bio- markers are evaluated, the majority require complex assay and not suitable for routine clinical practice [3, 4]. Hence, a sim- ple, cost-effective marker to predict response before initiation of neoadjuvant therapy is needed. Interaction between cancer and inflammatory cells is in- creasingly reported and neutrophil-to-lymphocyte ratio (NLR) is the widely evaluated inflammatory marker that has prognostic value in various cancer [5–8]. As neutrophil is a primary source of vascular endothelial growth factor (VEGF), neutrophilic infiltration of the tumor and an elevated NLR has been postulated to promote tumor growth and distant metas- tasis [9]. Recent meta-analyses have reported that high NLR was associated with poor overall survival in patients with esophageal carcinoma [10, 11]. However, its role in predicting * Raja Kalayarasan kalayarasanraja@yahoo.com 1 Department of Surgical Gastroenterology, JIPMER, Room no 5442, Fourth floor, Superspeciality block, Puducherry 605006, India 2 General surgery, JIPMER, Puducherry, India Journal of Gastrointestinal Cancer https://doi.org/10.1007/s12029-020-00445-5