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Neutrophil Lymphocyte Ratio (NLR) as a predictive factor radiological response of Neoadjuvant Chemotherapy (NAC) in Locally Advanced Rectal Cancer (LARC)

  • Adhitya Angga Wardhana ,
  • Tomy Lesmana ,


Background: Resistance of Neoadjuvant Chemotherapy (NAC) in Locally Advanced Rectal Cancer (LARC) makes patients lose their therapeutic window for tumor resection oncologically. As one of the inflammatory biomarkers, Neutrophil Lymphocyte Ratio (NLR) has a significant role in tumor progression. This study aims to evaluate the NLR values as a predictive factor radiological response of NAC in LARC.

Methods: This study used a cross-sectional study to assess the relationship of pre-chemotherapy NLR with NAC response. All subjects were LARC patients who underwent the NAC FOLFOX regiment at the Dr. Soetomo General Hospital from January 2016 to December 2020. Variables assessed in this study included tumor size (T), staging, pathology, metastasis status, Complete Blood Count (CBC) and abdominopelvic CT-scan examination before and after (3rd cycle) NAC FOLFOX regiment, after 3rd cycle NAC FOLFOX regiment, gender, and albumin level. Data were analyzed using SPSS version 23 for Windows.

Result: A total of 102 LARC patients underwent NAC. There were 62 patients (60.8%) with low pre-chemotherapy NLR (<2.15) and 40 patients (39.2%) with high pre-chemotherapy NLR (> 2.15). There were 57 patients with a positive response to NAC (Complete Response (CR)/Partial Response (PR)), with 48 patients have low NLR (84.2%) and 9 patients (15.8%) with high NLR. There was a significant relationship between pre-chemotherapy NLR and type of histopathology (OR 11.810; 95% CI: 4.561-30.579; p<0.001) to the radiological response of NAC in the Chi-Square test. However, a logistic regression test found that the OR value of pre-chemotherapy NLR increased to 13.649 (95% CI: 4.266-43.671; p<0.001) to the radiological response of NAC.

Conclusion: Pre-chemotherapy NLR can be used as one of the predictive factors of radiological response after the NAC FOLFOX regiment in LARC patients.


  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691.
  2. Salem ME, Hartley M, Unger K, Marshall JL. Neoadjuvant Combined-Modality Therapy for Locally Advanced Rectal Cancer and Its Future Direction. Oncology (Williston Park). 2016;30(6):546-562.
  3. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-23.
  4. Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016;62:132-7.
  5. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-444.
  6. Shrotriya S, Walsh D, Bennani-Baiti N, Thomas S, Lorton C. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review. PLoS One. 2015;10(12):e0143080.
  7. Tecchio C, Cassatella MA. Neutrophil-derived cytokines involved in physiological and pathological angiogenesis. Chem Immunol Allergy. 2014;99:123-137.
  8. Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, et al. Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 2012;72(16):3919-3927.
  9. Prabawa IPY, Bhargah A, Liwang F, Tandio DA, Tandio AL, Lestari AAW, et al. Pretreatment Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) as a Predictive Value of Hematological Markers in Cervical Cancer. Asian Pac J Cancer Prev. 2019;20(3):863-868.
  10. Wiranata S, Anjani IAW, Saputra IPGS, Sadvika IGAS, Prabawa IPY, Supadmanaba IG, et al. Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as a Stage Determination in Breast Cancer. Open Access Maced J Med Sci. 2020;8(B):1058-1063.
  11. Nemoto T, Endo S, Isohata N, Takayanagi D, Nemoto D, Aizawa M, et al Change in the neutrophil-to-lymphocyte ratio during chemotherapy may predict prognosis in patients with advanced or metastatic colorectal cancer. Mol Clin Oncol. 2021;14(5):107.
  12. Stojkovic Lalosevic M, Pavlovic Markovic A, Stankovic S, Stojkovic M, Dimitrijevic I, Radoman Vujacic I, et al. Combined Diagnostic Efficacy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of Systemic Inflammation in the Diagnosis of Colorectal Cancer. Dis Markers. 2019;2019:6036979.
  13. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860-867.
  14. Tan TP, Arekapudi A, Metha J, Prasad A, Venkatraghavan L. Neutrophil-lymphocyte ratio as predictor of mortality and morbidity in cardiovascular surgery: a systematic review. ANZ J Surg. 2015;85(6):414-419.
  15. Li H, Song J, Cao M, Wang G, Li L, Zhang B, et al. Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer. Int Immunopharmacol. 2016;40:327-331.
  16. Powell D, Tauzin S, Hind LE, Deng Q, Beebe DJ, Huttenlocher A. Chemokine Signaling and the Regulation of Bidirectional Leukocyte Migration in Interstitial Tissues. Cell Rep. 2017;19(8):1572-1585.
  17. Uribe-Querol E, Rosales C. Neutrophils in Cancer: Two Sides of the Same Coin. J Immunol Res. 2015;2015:983698.
  18. Shibutani M, Maeda K, Nagahara H, Noda E, Ohtani H, Nishiguchi Y, et al. A high preoperative neutrophil-to-lymphocyte ratio is associated with poor survival in patients with colorectal cancer. Anticancer Res. 2013;33(8):3291-4.
  19. Jia W, Wu J, Jia H, Yang Y, Zhang X, Chen K, et al. The Peripheral Blood Neutrophil-To-Lymphocyte Ratio Is Superior to the Lymphocyte-To-Monocyte Ratio for Predicting the Long-Term Survival of Triple-Negative Breast Cancer Patients. PLoS One. 2015;10(11):e0143061.
  20. Chen Y, Chen K, Xiao X, Nie Y, Qu S, Gong C, et al. Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. BMC Cancer. 2016;16:320.
  21. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2014 May 15;134(10):2403-13.
  22. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14.
  23. Myojin M, Horimoto Y, Ito M, Kitano S, Ishizuka Y, Sasaki R, et al. Neutrophil-to-lymphocyte ratio and histological type might predict clinical responses to eriburin-based treatment in patients with metastatic breast cancer. Breast Cancer. 2020;27(4):732-738.
  24. Ashwath KG, Aggarwal A, Praneeth K, Singla N, Gupta K. Neutrophil-to-Lymphocyte Ratio: Can It Be Used as an Adjunct Tool to Predict Histopathological Grade of Brain Tumor?. J Neurosci Rural Pract. 2019;10(4):648-652.
  25. Lee JH, Park B, Joo J, Kook MC, Kim YI, Lee JY, et al. Body mass index and mortality in patients with gastric cancer: a large cohort study. Gastric Cancer. 2018;21(6):913-924.

How to Cite

Wardhana, A. A., & Lesmana, T. (2021). Neutrophil Lymphocyte Ratio (NLR) as a predictive factor radiological response of Neoadjuvant Chemotherapy (NAC) in Locally Advanced Rectal Cancer (LARC). Bali Medical Journal, 10(2), 717–723.




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Adhitya Angga Wardhana
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Tomy Lesmana
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BMJ Journal