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)].
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).
In patients with locally advanced esophageal SCC, NLR is not a useful marker to predict pathologic response to nCRT.
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Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen M, Wijnhoven BPL, van Laarhoven H, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, ten Kate F, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen M, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij C, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, CROSS study group; CROSS study group (2015). Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098.
Sjoquist KM, Burmeister BH, Smithers BM, et al; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.
Chiam K, Mayne GC, Watson DI, Woodman RJ, Bright TF, Michael MZ, et al. Identification of microRNA biomarkers of response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma using next generation sequencing. Ann Surg Oncol. 2018;25:2731–8.
Wong C, Law S. Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer. J Thorac Dis. 2017;9:S773–80.
Carruthers R, Tho LM, Brown J, Kakumanu S, McCartney E, McDonald AC. Systemic inflammatory response is a predictor of outcome in patients undergoing preoperative chemoradiation for locally advanced rectal cancer. Color Dis. 2012;14:e701–7.
Kim YJ, Lee I, Chung YS, Nam EJ, Kim S, Kim SW, et al. Pretreatment neutrophil-to-lymphocyte ratio and its dynamic change during neoadjuvant chemotherapy as poor prognostic factors in advanced ovarian cancer. Obstet Gynecol Sci. 2018;61:227–34.
Liu D, Huang Y, Li L, Song J, Zhang L, Li W. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer. 2017;17:882.
Clarke KV, Amir E, Berman HK, Maganti M, Sridhar SS. Association between pretreatment neutrophil to lymphocyte ratio (NLR) and complete pathological response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy (NACT). J Clin Oncol. 2015;33:e11588.
Kusumanto YH, Dam WA, Hospers GA, et al. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6:283–7.
Pirozzolo G, Gisbertz SS, Castoro C, van Berge Henegouwen MI, Scarpa M. Neutrophil-to-lymphocyte ratio as prognostic marker in esophageal cancer: a systematic review and meta-analysis. J Thorac Dis. 2019;11:3136–45.
Zhang X, Jiang Y, Wang Y, Wang Z, Zhao L, Xue X, et al. Prognostic role of neutrophil-lymphocyte ratio in esophageal cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97:e13585.
Miyata H, Yamasaki M, Kurokawa Y, et al. Prognostic value of an inflammation-based score in patients undergoing pre-operative chemotherapy followed by surgery for esophageal cancer. Exp Ther Med. 2011;2:879–85.
Sato H, Yasuhiro T, Kawano T. Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg. 2012;36:617–22.
Powell AGMT, Chin C, Coxon AH, Chalishazar A, Christian A, Roberts SA, et al. Neutrophil to lymphocyte ratio as a predictor of response to neoadjuvant chemotherapy and survival in oesophageal adenocarcinoma. BJS Open. [Epub ahead of print]. 2020;4:416–23.
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen M, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.
Sagiv JY, Michaeli J, Assi S, Mishalian I, Kisos H, Levy L, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015;10:562–73.
Giese MA, Hind LE, Huttenlocher A. Neutrophil plasticity in the tumor microenvironment. Blood. 2019;133:2159–67.
Peters JH, Meester TR, Stein HJ. Surgical therapy for cancer of the esophagus and cardia (1995). In: Castell DO; Ed. The Esophagus, 2nd ed. New York: Little, Brown. p.293–335.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
Sasikumar K, Kalayarasan R, Gnanasekaran S, et al (2020). Minimally invasive oesophagectomy with a total two-field lymphadenectomy after neoadjuvant chemoradiotherapy for locally advanced squamous cell carcinoma of the oesophagus: a prospective study. J minim access Surg Jan 9 [Epub ahead of print].
Anand S, Kalayarasan R, Chandrasekar S, Gnanasekaran S, Pottakkat B. Minimally invasive esophagectomy with thoracic duct resection post neoadjuvant chemoradiotherapy for carcinoma esophagus-impact on lymph node yield and hemodynamic parameters. J Gastrointest Cancer. 2019;50:230–5.
Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic Correlations Cancer. 1994;73:2680–6.
Amin MB, Edge S, Greene F, et al. (Eds.). AJCC cancer staging manual (8th edition). Springer International Publishing: American Joint Commission on Cancer; 2017.
Miyata H, Sugimura K, Yamasaki M, Makino T, Tanaka K, Morii E, et al. Clinical impact of the location of lymph node metastases after neoadjuvant chemotherapy for middle and lower thoracic esophageal cancer. Ann Surg Oncol. 2019;26:200–8.
Martin A, Seignez C, Racoeur C, Isambert N, Mabrouk N, Scagliarini A, et al. Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid a treatment. Oncotarget. 2018;9:28364–78.
Finisguerra V, Di Conza G, Di Matteo M, et al. MET is required for the recruitment of anti-tumoural neutrophils. Nature. 2015;522:349–53.
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Anand, S., Bhati, G., Gurram, R. et al. Does Neutrophil-to-Lymphocyte Ratio (NLR) Predict Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma?. J Gastrointest Canc (2020). https://doi.org/10.1007/s12029-020-00445-5
- Neutrophil-to-lymphocyte ratio
- Esophageal cancer
- Neoadjuvant therapy
- Squamous cell carcinoma