Research Article
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Year 2023, Volume: 5 Issue: 3, 227 - 236, 28.07.2023
https://doi.org/10.38053/acmj.1290362

Abstract

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2016;66:7-30. doi: 10.3322/caac.21332
  • Rödel RM, Steiner W, Müller RM, Kron M, Matthias C. Endoscopic laser surgery of early glottic cancer: involvement of the anterior commissure. Head Neck. 2009;31:583-592. doi: 10.1002/hed.20993
  • Patel KB, Nichols AC, Fung K, Yoo J, MacNeil SD. Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy. J Otolaryngol Head Neck Surg. 2018;47:19. doi: 10.1186/s40463-018-0262-2.
  • Warner L, Chudasama J, Kelly CG, et al. Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev. 2014:CD002027. doi: 10.1002/14651858.CD002027.pub2
  • Aaltonen LM, Rautiainen N, Sellman J, et al. Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy. Int J Radiat Oncol Biol Phys. 2014;90:255-260. doi: 10.1016/j.ijrobp.2014.06.032
  • Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091-2098. doi: 10.1056/NEJMoa031317
  • Department of Veterans Affairs Laryngeal Cancer Study Group, Wolf GT, Fisher SG, Hong WK, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324:1685-1690. doi: 10.1056/NEJM19910613324240
  • Cooper JS, Pajak TF, Forastiere AA,et al. Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937-1944. doi: 10.1056/NEJMoa032646
  • Patel SG, Lydiatt WM, Glastonbury CM, et al. Larynx. In: Amin MB, ed, American Joint Committee on Cancer staging manual, 8th edn. NewYork: Springer. 2017;149–163.
  • Lewis CM, Chinn SB, Holsinger C, Weber RS. Cancer of the Larynx: Tis, T1, T2 Evaluation and Management. In: Bernier J, eds, Head and neck cancer multimodality management, 2nd edn. Switzerland: Springer. 2016;539–554.
  • Becker A, Stadler P, Lavey RS, et al. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2000;46:459-466. doi: 10.1016/s0360-3016(99)00384-3
  • Melo-Alvim C, Miguel-Semedo P, Paiva RS, et al. Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma. Rep Pract Oncol Radiother. 2020;25:768-774. doi: 10.1016/j.rpor.2020.07.002
  • Galdiero MR, Marone G, Mantovani A. Cancer inflammation and cytokines. Cold Spring Harb Perspect Biol. 2018;10:a028662. doi: 10.1101/cshperspect.a028662.
  • Colloca G, Venturino A, Guarneri D. Neutrophil-to-lymphocyte ratio predicts survival of patients with rectal cancer receiving neo-adjuvant chemoradiation followed by radical resection: a meta-analysis. Expert Rev Anticancer Ther. 2023;23:421-429. doi: 10.1080/14737140.2023.2194635
  • Gong Z, Xin R, Li L, Lv L, Wu X. Platelet-to-lymphocyte ratio associated with the clinicopathological features and prognostic value of breast cancer: a meta-analysis. Int J Biol Markers. 2022;37:339-348. doi: 10.1177/03936155221118098
  • Zeng Z, Xu S, Wang D, Qin G. Prognostic significance of systemic immune-inflammation index in patients with nasopharyngeal carcinoma: a meta-analysis. Syst Rev. 2022;11:247. doi: 10.1186/s13643-022-02123-y
  • Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL. Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev. 2015;34:735-751. doi: 10.1007/s10555-015-9594-9
  • Metelli A, Wu BX, Riesenberg B, et al. Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β. Sci Transl Med. 2020;12:eaay4860. doi: 10.1126/scitranslmed.aay4860
  • Shankaran V, Ikeda H, Bruce AT, et al. Pillars article: IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. J Immunol. 2018;201:827-831.
  • Yang L, Huang Y, Zhou L, Dai Y, Hu G. High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta-analysis. Head Neck. 2019;41:1525-1535. doi: 10.1002/hed.25583
  • Cho Y, Kim JW, Yoon HI, Lee CG, Keum KC, Lee IJ. The prognostic significance of neutrophil-to-lymphocyte ratio in head and neck cancer patients treated with radiotherapy. J Clin Med. 2018;7:512. doi: 10.3390/jcm7120512
  • Sung S, Son SH, Park EY, Kay CS. Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy. PLoS One. 2017;12:e0173955. doi: 10.1371/journal.pone.0173955
  • Fu Y, Liu W, OuYang D, Yang A, Zhang Q. Preoperative neutrophil-to-lymphocyte ratio predicts long-term survival in patients undergoing total laryngectomy with advanced laryngeal squamous cell carcinoma: a single-center retrospective study. Medicine (Baltimore). 2016;95:e2689. doi: 10.1097/MD.0000000000002689
  • Mao Y, Fu Y, Gao Y, Yang A, Zhang Q. Platelet-to-lymphocyte ratio predicts long-term survival in laryngeal cancer. Eur Arch Otorhinolaryngol. 2018;275:553-559. doi: 10.1007/s00405-017-4849-4
  • Li Z, Qu Y, Yang Y, et al. Prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with laryngeal squamous cell carcinoma. Clin Otolaryngol. 2021;46:395-405. doi: 10.1111/coa.13689
  • Bojaxhiu B, Templeton AJ, Elicin O, et al. Relation of baseline neutrophil-to-lymphocyte ratio to survival and toxicity in head and neck cancer patients treated with (chemo-) radiation. Radiat Oncol. 2018;13:216. doi: 10.1186/s13014-018-1159-y
  • Zeng YC, Chi F, Xing R, et al. Pre-treatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Jpn J Clin Oncol. 2016;46:126-131. doi: 10.1093/jjco/hyv175
  • Atasever Akkas E, Yucel B. Prognostic value of systemic ımmune ınflammation ındex in patients with laryngeal cancer. Eur Arch Otorhinolaryngol. 2021;278:1945-1955. doi: 10.1007/s00405-021-06798-2
  • Kotha NV, Voora RS, Qian AS, et al. Prognostic utility of pretreatment neutrophil-lymphocyte ratio in advanced larynx cancer. Biomark Insights. 2021;16:11772719211049848. doi: 10.1177/11772719211049848
  • Baumann R, Depping R, Delaperriere M, Dunst J. Targeting hypoxia to overcome radiation resistance in head & neck cancers: real challenge or clinical fairytale? Expert Rev Anticancer Ther. 2016;16:751-758. doi: 10.1080/14737140.2016.1192467.
  • Overgaard J, Hansen HS, Andersen AP, et al. Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys 1989;16:1065-1068. doi: 10.1016/0360-3016(89)90917-6
  • Warde P, O’Sullivan B, Bristow RG, et al. T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control. Int J Radiat Oncol Biol Phys 1998;41:347-353. doi: 10.1016/s0360-3016(98)00062-5
  • Grant DG, Hussain A, Hurman D. Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy. J Laryngol Otol 1999;113(9):829-833. doi: 10.1017/s0022215100145323
  • van Acht MJ, Hermans J, Boks DE, Leer JW. The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma. Radiother Oncol 1992;23:229-235. doi: 10.1016/s0167-8140(92)80126-4
  • Su NW, Liu CJ, Leu YS, Lee JC, Chen YJ, Chang YF. Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients. Onco Targets Ther. 2015;8:251-258. doi: 10.2147/OTT.S70204
  • Pogorzelski M, Hilser T, Ting SC, et al. Identification of a prognostic clinical score for patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with systemic therapy including cetuximab. Front Oncol. 2021;13:635096. doi: 10.3389/fonc.2021.635096
  • Gorphe P, Bouhir S, Garcia GCTE, et al. Anemia and neutrophil-to-lymphocyte ratio in laryngeal cancer treated with induction chemotherapy. Laryngoscope. 2020;130:144-150. doi: 10.1002/lary.28021
  • Xu H, Zheng X, Ai J, Yang L. Hemoglobin, albumin, lymphocyte, and platelet (HALP) score and cancer prognosis: a systematic review and meta-analysis of 13,110 patients. Int Immunopharmacol. 2023;114:109496. doi: 10.1016/j.intimp.2022.109496
  • Farag CM, Antar R, Akosman S, Ng M, Whalen MJ. What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? a comprehensive literature review of HALP’s prognostic ability in different cancer types. Oncotarget. 2023;14:153-172. doi: 10.18632/oncotarget.28367.

The association of anemia and high neutrophil-lymphocyte ratio with decreased survival in patients with laryngeal cancer treated with radiotherapy

Year 2023, Volume: 5 Issue: 3, 227 - 236, 28.07.2023
https://doi.org/10.38053/acmj.1290362

Abstract

Aims: We aimed to examine the prognostic value of inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and anemia on oncological outcomes in patients with laryngeal squamous cell carcinomas (LSCC) treated with radiotherapy.
Methods: 213 LSCC patients analyzed retrospectively. Inflammatory markers were established by examining blood samples taken within 7 days before treatment. Patients were categorized into two groups: low and high according to NLR, PLR, and SII threshold values. In addition, to evaluate the effect of hemoglobin (Hb) level, the threshold value of each inflammatory marker and Hb level were combined, and 3 groups were formed (3 groups for NLR, 3 groups for PLR, and 3 groups for SII). The relationship between inflammatory markers and overall survival (OS), disease-free survival (DFS), and local regional recurrence-free survival (LRRFS) was investigated.
Results: In univariate analysis, high NLR, PLR, SII, and low Hb (<13 g/dl) level were associated with worse survival (all p<0.022), except for PLR and Hb for LRRFS. OS and DFS were significantly better in patients in each group A with a low inflammatory index and high Hb (all p<0.013). In the multivariate analysis, high NLR and group CNLR (high NLR with low Hb) were statistically significant predictors of decreased OS (HR 1.85, 95% CI 1.05-3.28, p=0.033; HR 2.61, 95% CI 1.14-5.97, p=0.022) and DFS (HR 1.81, 95% CI 1.11-2.96, p=0.017; HR 3.32, 95% CI 1.20-9.16, p=0.028).
Conclusion: NLR may serve as a potential prognostic biomarker in LSCC, and its predictive ability is further enhanced when NLR is combined with Hb level.

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2016;66:7-30. doi: 10.3322/caac.21332
  • Rödel RM, Steiner W, Müller RM, Kron M, Matthias C. Endoscopic laser surgery of early glottic cancer: involvement of the anterior commissure. Head Neck. 2009;31:583-592. doi: 10.1002/hed.20993
  • Patel KB, Nichols AC, Fung K, Yoo J, MacNeil SD. Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy. J Otolaryngol Head Neck Surg. 2018;47:19. doi: 10.1186/s40463-018-0262-2.
  • Warner L, Chudasama J, Kelly CG, et al. Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev. 2014:CD002027. doi: 10.1002/14651858.CD002027.pub2
  • Aaltonen LM, Rautiainen N, Sellman J, et al. Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy. Int J Radiat Oncol Biol Phys. 2014;90:255-260. doi: 10.1016/j.ijrobp.2014.06.032
  • Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091-2098. doi: 10.1056/NEJMoa031317
  • Department of Veterans Affairs Laryngeal Cancer Study Group, Wolf GT, Fisher SG, Hong WK, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324:1685-1690. doi: 10.1056/NEJM19910613324240
  • Cooper JS, Pajak TF, Forastiere AA,et al. Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937-1944. doi: 10.1056/NEJMoa032646
  • Patel SG, Lydiatt WM, Glastonbury CM, et al. Larynx. In: Amin MB, ed, American Joint Committee on Cancer staging manual, 8th edn. NewYork: Springer. 2017;149–163.
  • Lewis CM, Chinn SB, Holsinger C, Weber RS. Cancer of the Larynx: Tis, T1, T2 Evaluation and Management. In: Bernier J, eds, Head and neck cancer multimodality management, 2nd edn. Switzerland: Springer. 2016;539–554.
  • Becker A, Stadler P, Lavey RS, et al. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2000;46:459-466. doi: 10.1016/s0360-3016(99)00384-3
  • Melo-Alvim C, Miguel-Semedo P, Paiva RS, et al. Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma. Rep Pract Oncol Radiother. 2020;25:768-774. doi: 10.1016/j.rpor.2020.07.002
  • Galdiero MR, Marone G, Mantovani A. Cancer inflammation and cytokines. Cold Spring Harb Perspect Biol. 2018;10:a028662. doi: 10.1101/cshperspect.a028662.
  • Colloca G, Venturino A, Guarneri D. Neutrophil-to-lymphocyte ratio predicts survival of patients with rectal cancer receiving neo-adjuvant chemoradiation followed by radical resection: a meta-analysis. Expert Rev Anticancer Ther. 2023;23:421-429. doi: 10.1080/14737140.2023.2194635
  • Gong Z, Xin R, Li L, Lv L, Wu X. Platelet-to-lymphocyte ratio associated with the clinicopathological features and prognostic value of breast cancer: a meta-analysis. Int J Biol Markers. 2022;37:339-348. doi: 10.1177/03936155221118098
  • Zeng Z, Xu S, Wang D, Qin G. Prognostic significance of systemic immune-inflammation index in patients with nasopharyngeal carcinoma: a meta-analysis. Syst Rev. 2022;11:247. doi: 10.1186/s13643-022-02123-y
  • Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL. Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev. 2015;34:735-751. doi: 10.1007/s10555-015-9594-9
  • Metelli A, Wu BX, Riesenberg B, et al. Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β. Sci Transl Med. 2020;12:eaay4860. doi: 10.1126/scitranslmed.aay4860
  • Shankaran V, Ikeda H, Bruce AT, et al. Pillars article: IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. J Immunol. 2018;201:827-831.
  • Yang L, Huang Y, Zhou L, Dai Y, Hu G. High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta-analysis. Head Neck. 2019;41:1525-1535. doi: 10.1002/hed.25583
  • Cho Y, Kim JW, Yoon HI, Lee CG, Keum KC, Lee IJ. The prognostic significance of neutrophil-to-lymphocyte ratio in head and neck cancer patients treated with radiotherapy. J Clin Med. 2018;7:512. doi: 10.3390/jcm7120512
  • Sung S, Son SH, Park EY, Kay CS. Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy. PLoS One. 2017;12:e0173955. doi: 10.1371/journal.pone.0173955
  • Fu Y, Liu W, OuYang D, Yang A, Zhang Q. Preoperative neutrophil-to-lymphocyte ratio predicts long-term survival in patients undergoing total laryngectomy with advanced laryngeal squamous cell carcinoma: a single-center retrospective study. Medicine (Baltimore). 2016;95:e2689. doi: 10.1097/MD.0000000000002689
  • Mao Y, Fu Y, Gao Y, Yang A, Zhang Q. Platelet-to-lymphocyte ratio predicts long-term survival in laryngeal cancer. Eur Arch Otorhinolaryngol. 2018;275:553-559. doi: 10.1007/s00405-017-4849-4
  • Li Z, Qu Y, Yang Y, et al. Prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with laryngeal squamous cell carcinoma. Clin Otolaryngol. 2021;46:395-405. doi: 10.1111/coa.13689
  • Bojaxhiu B, Templeton AJ, Elicin O, et al. Relation of baseline neutrophil-to-lymphocyte ratio to survival and toxicity in head and neck cancer patients treated with (chemo-) radiation. Radiat Oncol. 2018;13:216. doi: 10.1186/s13014-018-1159-y
  • Zeng YC, Chi F, Xing R, et al. Pre-treatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Jpn J Clin Oncol. 2016;46:126-131. doi: 10.1093/jjco/hyv175
  • Atasever Akkas E, Yucel B. Prognostic value of systemic ımmune ınflammation ındex in patients with laryngeal cancer. Eur Arch Otorhinolaryngol. 2021;278:1945-1955. doi: 10.1007/s00405-021-06798-2
  • Kotha NV, Voora RS, Qian AS, et al. Prognostic utility of pretreatment neutrophil-lymphocyte ratio in advanced larynx cancer. Biomark Insights. 2021;16:11772719211049848. doi: 10.1177/11772719211049848
  • Baumann R, Depping R, Delaperriere M, Dunst J. Targeting hypoxia to overcome radiation resistance in head & neck cancers: real challenge or clinical fairytale? Expert Rev Anticancer Ther. 2016;16:751-758. doi: 10.1080/14737140.2016.1192467.
  • Overgaard J, Hansen HS, Andersen AP, et al. Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys 1989;16:1065-1068. doi: 10.1016/0360-3016(89)90917-6
  • Warde P, O’Sullivan B, Bristow RG, et al. T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control. Int J Radiat Oncol Biol Phys 1998;41:347-353. doi: 10.1016/s0360-3016(98)00062-5
  • Grant DG, Hussain A, Hurman D. Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy. J Laryngol Otol 1999;113(9):829-833. doi: 10.1017/s0022215100145323
  • van Acht MJ, Hermans J, Boks DE, Leer JW. The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma. Radiother Oncol 1992;23:229-235. doi: 10.1016/s0167-8140(92)80126-4
  • Su NW, Liu CJ, Leu YS, Lee JC, Chen YJ, Chang YF. Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients. Onco Targets Ther. 2015;8:251-258. doi: 10.2147/OTT.S70204
  • Pogorzelski M, Hilser T, Ting SC, et al. Identification of a prognostic clinical score for patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with systemic therapy including cetuximab. Front Oncol. 2021;13:635096. doi: 10.3389/fonc.2021.635096
  • Gorphe P, Bouhir S, Garcia GCTE, et al. Anemia and neutrophil-to-lymphocyte ratio in laryngeal cancer treated with induction chemotherapy. Laryngoscope. 2020;130:144-150. doi: 10.1002/lary.28021
  • Xu H, Zheng X, Ai J, Yang L. Hemoglobin, albumin, lymphocyte, and platelet (HALP) score and cancer prognosis: a systematic review and meta-analysis of 13,110 patients. Int Immunopharmacol. 2023;114:109496. doi: 10.1016/j.intimp.2022.109496
  • Farag CM, Antar R, Akosman S, Ng M, Whalen MJ. What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? a comprehensive literature review of HALP’s prognostic ability in different cancer types. Oncotarget. 2023;14:153-172. doi: 10.18632/oncotarget.28367.
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Details

Primary Language English
Subjects Clinical Oncology, Health Care Administration
Journal Section Research Articles
Authors

Ela Delikgöz Soykut 0000-0003-1225-8458

Yasemin Kemal 0000-0002-1175-9085

Serkan Kaplan 0000-0003-1465-7145

Cengiz Karaçin 0000-0002-7310-9328

Eylem Odabaşı 0000-0002-1531-4622

Asude Unal 0000-0003-0282-8277

Zehra Er 0000-0002-3627-5079

Suheyla Aytaç Arslan 0000-0002-6479-0051

Yıldız Guney 0000-0002-0756-9246

Early Pub Date July 26, 2023
Publication Date July 28, 2023
Published in Issue Year 2023 Volume: 5 Issue: 3

Cite

AMA Delikgöz Soykut E, Kemal Y, Kaplan S, Karaçin C, Odabaşı E, Unal A, Er Z, Aytaç Arslan S, Guney Y. The association of anemia and high neutrophil-lymphocyte ratio with decreased survival in patients with laryngeal cancer treated with radiotherapy. Anatolian Curr Med J / ACMJ / acmj. July 2023;5(3):227-236. doi:10.38053/acmj.1290362

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