Sınırlı evre küçük hücreli akciğer kanseri tanılı hastalarda eşzamanlı kemoradyoterapi öncesi sistemik immün inflamasyon indeksi’nin sağ kalıma etkisi

Year 2021, Volume: 14 Issue: 2, 186 - 198, 25.08.2021

Ahmet Küçük , Şükran Eskici Öztep , Eda Bengi Yılmaz , Erkan Topkan

https://doi.org/10.26559/mersinsbd.842266

Abstract

Amaç: Birçok çalışmada, nötrofil (N), trombosit (T) ve lenfosit (L) bazlı sistemik immün inflamasyon indeksinin (Sİİ) çeşitli solid tümör tiplerin de sağ kalım sonuçlarını öngörebildiği gösterilmiştir. Daha önce sadece SE-KHAK hastalarından oluşan gruplarda eşzamanlı kemoradyoterapi (E-KRT) öncesi Sİİ’nin prognostik önemini araştıran çalışma olmaması nedeniyle Sİİ’nin bu hasta grubundaki prognostik önemini araştırmayı amaçladık. Yöntem: Ocak 2007-Aralık 2018 tarihleri arasında iki radyasyon onkolojisi merkezinde E-KRT ile tedavi edilen SE-KHAK hastalarını içeren retrospektif veriler analiz edilmiştir. Sİİ değerleri E-KRT'nin başlamasından önceki 7 gün içerisinde elde edilen toplam 139 hastanın periferik kan örneklerinde Sİİ = N×T/L formülü kullanılarak hesaplandı. Çalışma popülasyonunu farklı genel sağ kalım (GS) sonuçlarına sahip iki gruba ayırabilecek tedavi öncesi Sİİ’nin optimal eşik değeri receiver operating characteristic (ROC) analizi ile değerlendirildi. Genel sağ kalım (GS) Kaplan-Meier eğrileri kullanılarak bulunmuştur. Birincil sonlanım noktası Sİİ değeri ve GS sonuçları arasındaki ilişkiydi. Bulgular: Tedavi öncesi Sİİ’nin optimal eşik değeri 524 olarak bulunan hastalar iki gruba ayrılmıştır [Eğri altındaki alan (AAA): %68.1; duyarlılık: %68.6; özgüllük: %66.4]: Grup 1: Sİİ<524 (N=65) ve Grup 2: Sİİ≥524 (N=74). İki Sİİ grubu arasındaki Kaplan-Meier karşılaştırmaları Sİİ <524 grubunda Sİİ ≥524’ten anlamlı düzeyde daha uzun GS olduğunu (sırasıyla 34.6’ya karşı 12.5 ay; p<0.001) gösterdi. Benzer şekilde, 5- (%32'ye karşılık %8.9) ve 8 yıllık (%15'e karşılık %6) GS oranları da Sİİ<524 grubunda daha iyiydi. Çok değişkenli analizler sonucunda Sİİ’nin GS (p <0.001) için bağımsız bir prognostik faktör olduğu görülmüştür. Sonuç: Bu retrospektif analiz sonuçları tedavi öncesi Sİİ’nin, E-KRT ile tedavi edilen SE-KHAK hastaları için güçlü ve bağımsız bir prognostik biyobelirteç olduğunu göstermiştir.

Keywords

Küçük hücreli akciğer kanseri, Sistemik İmmün İnflamasyon İndeksi, Prognoz, Genel sağ kalım

Supporting Institution

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Project Number

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Thanks

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The effect of systemic immune inflammation index on survival before concurrent chemoradiotherapy in patients diagnosed with limited stage small cell lung cancer

Abstract

Aim: In many retrospective studies, it has been shown that neutrophil (N), platelet (P) and lymphocyte (L) based systemic immune inflammation index (Sİİ) can predict survival outcomes of various solid tumor types. For this purpose, we wanted to evaluate the prognostic importance of SII in LS-SCLC patients treated with concurrent chemoradiotherapy (C-CRT). Method: Retrospective data including LS-SCLC patients treated with C-CRT in two radiation oncology centers between January 2007 and December 2018 were analyzed. SII was calculated using the formula Sİİ = N × P / L in peripheral blood samples of a total of 139 patients in the last ≤ 7 days before the initiation of C-CRT. The optimal cut-off value of SII before treatment which can stratify the study population into two groups with different overall survival (OS) results, was evaluated by receiver operating characteristic (ROC) curve analysis. OS was estimated using Kaplan-Meier curves and Cox regression models. The primary endpoint was the relationship between the SII value and the OS results. Results: The optimal cut-off value of pre-treatment SII was found to be 594. [Area under the curve (AUC): 68.1%; sensitivity: 68.6%; specificity: 66.4%,]: Group 1: SII<524 (N=65) and Group 2: SII≥524 (N=74). Kaplan-Meier comparisons between the two SII groups showed that the SII<524 cohort had significantly longer OS than SII≥524 (34.6 vs. 12.5 months, respectively; p<0.001). Similarly, OS rates of 5 (32% vs. 8.9%) and 8-year (15% vs. 6%) were better in the SII<524 cohort. Results of multivariate analysis revealed the pretreatment SII as an independent prognostic factor for OS (p <0.001). Conclusion: These retrospective analysis results showed that pre-treatment SII is a strong prognostic biomarker for LS-SCLC patients treated with C-CRT.

Keywords

Small cell lung cancer, systemic immune inflammation index, prognosis, overall survival

Project Number

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References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69(1):7-34. doi:10.3322/caac.21551.
• 2. Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat. Rev. Cancer 2017;17(12):725–737. doi:10.1038/nrc.2017.87.
• 3. Rudin CM, Poirier JT. Small-cell lung cancer in 2016: Shining light on novel targets and therapies. Nat Rev Clin Oncol 2017;14(2):75–76. doi:10.1038/nrclinonc.2016.203.
• 4. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24(28):4539-44. doi: 10.1200/jco.2005.04.4859.
• 5. Van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 2011; 378(9804): 1741-55. doi:10.1016/S0140-6736(11)60165-7.
• 6. Turrisi AT, Kim K, Blum R et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999; 340: 265-71. doi:10.1002/1097-0142
• 7. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 1999; 341:476-84.
• 8. Johnson BE, Bridges JD, Sobczeck M et al. Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol. 1996; 14: 806-13.
• 9. De Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer2006;6(1):24-37. doi:10.1038/nrc1782
• 10. Mantovani A, Allavena P. Sica A, et al. Cancer-related inflammation. Nature 2008;454(7203):436-44. doi:10.1038/nature07205
• 11. Placke T, Salih HR, Kopp HG. GITR ligand provided by thrombopoietic cells inhibits NK cell antitumor activity. J. Immunol.2012;189(1):154–160. doi.10.4049/jimmunol.1103194
• 12. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial–mesenchymal-like transition and promotes metastasis. Cancer Cell 2011;20(5):576–590. doi:10.1016/j.ccr.2011.09.009
• 13. Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 2013;24(1):130–137. doi:10.1016/j.ccr.2013.05.008
• 14. Gil-Bernabe AM, Ferjancic S, Tlalka M et al. Recruitment of monocytes/ macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood 2012;119(13):3164–3175. doi:10.1182/blood-2011-08-376426
• 15. Zhou T, Zhan J, Hong S, et al. Ratio of C-reactive protein/albumin is an inflammatory prognostic score for predicting overall survival of patients with small-cell lung cancer. Sci Rep. 2015;5:10481. doi:10.1038/srep10481
• 16. He X, Zhou T, Yang Y, et al. Advanced lung cancer inflammation index, a new prognostic score, predicts outcome in patients with small-cell lung cancer. Clin Lung Cancer.2015;16(6): 165-171. doi:10.1016/j.cllc.2015.03.005
• 17. Kim EY, Kim N, Kim YS, et al. Prognostic significance of modified advanced lung cancer inflammation index (ALI) in patients with small cell lung cancer_ comparison with original ALI. PLoS One. 2016;11(10):0164056. doi:10.1371/journal.pone.0164056
• 18. 18. Suzuki R, Wei X, Allen PK, et al. Prognostic significance of total lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in limited-stage small-cell lung cancer. Clin Lung Cancer. 2019;20(2):117-23. doi:10.1016/j.cllc.2018.11.013
• 19. Wang X. Jiang R. Li K. Prognostic significance of pretreatment laboratory parameters in combined small-cell lung cancer. Cell BiochemBiophys. 2014; 69: 633-40. doi.10.1007/s12013-014-9845-3.
• 20. Deng M. Ma X. Liang X. Zhu C. Wang M. Are pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio useful in predicting the outcomes of patients with small-cell lung cancer? Oncotarget. 2017; 8: 37200-7. doi:10.18632/oncotarget.16553
• 21. Jin S, Cao S, Xu S, Wang C, Meng Q, Yu Y. Clinical impact of pretreatment prognostic nutritional index (PNI) in small cell lung cancer patients treated with platinum-based chemotherapy. Clin. RespirJ.2018;12(9):2433-40. doi:10.1111/crj.12925
• 22. Bernhardt D, Aufderstrasse S, Konig L, et al. Impact of inflammatory markers on survival in patients with limited disease small-cell lung cancer undergoing chemoradiotherapy. Cancer Manage Res. 2018;10:6563–69. doi:10.2147/CMAR.S180990
• 23. Wang C, Jin S, Xu S, et al. High systemic immune-inflammation index (Sİİ) represents an unfavorable prognostic factor for small cell lung cancer treated with etoposide and platinum-based chemotherapy. Lung 2020; 198: 405-14. doi:10.1007/s00408-020-00333-6
• 24. Sonehara K, Tateishi K, Komatsu M, et al. Modified Glasgow prognostic score as a prognostic factor in patients with extensive disease-small-cell lung cancer: a retrospective study in a single institute. Chemotherapy.2019;64(3):129-37. doi:10.1159/000502681
• 25. Qi Q, Zhuang L, Shen Y, et al. A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer. 2016; 122(14): 2158-67. doi:10.1002/cncr.30057
• 26. Geng Y, Zhu D, Wu C, et al. A novel systemic inflammation response index (SIRI) for predicting postoperative survival of patients with esophageal squamous cell carcinoma. Int Immunopharmacol. 2018; 65: 503-10. doi:10.1016/j.intimp.2018.10.002
• 27. Chen Y, Jiang W, Xi D, et al. Development and validation of nomogram based on SIRI for predicting the clinical outcome in patients with nasopharyngeal carcinomas. J Investig Med. 2019; 67(3): 691-8.doi:10.1136/jim-2018-000801
• 28. Xu L, Yu S, Zhuang L, et al. Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients. Oncotarget. 2017; 8(21):34954-60. doi:10.18632/oncotarget.16865
• 29. Hu B, Yang XR, Xu Y et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin. Cancer Res. 2014: 20(23), 6212–6222. doi.10.1158/1078-0432.CCR-14-0442
• 30. Fankhauser CD, Sander S, Roth L et al. Systemic inflammatory markers have independent prognostic value in patients with metastatic testicular germ cell tumours undergoing first-line chemotherapy. Br. J. Cancer 2018;118(6):825–830. doi.10.1038/bjc.2017.467
• 31. Chen JH, Zhai ET, Yuan YJ et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J. Gastroenterol. 2017; 23(34): 6261–6272. doi:10.3748/wjg.v23.i34.6261
• 32. Wang K, Diao F, Ye Z et al. Prognostic value of systemic immune-inflammation index in patients with gastric cancer. Chin. J. Cancer 2017; 36(1):75. doi:10.1186/s40880-017-0243-2
• 33. Geng Y, Shao Y, Zhu D et al. Systemic immune-inflammation index predicts prognosis of patients with esophageal squamous cell carcinoma: a propensity score-matched analysis. Sci. Rep. 2016; 6: 39482. doi:10.1038/srep39482
• 34. Fan L, Wang R, Chi C et al. Systemic immune-inflammation index predicts the combined clinical outcome after sequential therapy with abiraterone and docetaxel for metastatic castration-resistant prostate cancer patients. Prostate2018;78(4):250–256. doi:10.1002/pros.23465
• 35. Wang L, Wang C, Wang J, Huang X, Cheng Y. A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma. J. Cancer Res. Clin. Oncol. 2017;143(10):2077–2086. doi:10.1007/s00432-017-2451-1
• 36. Jiang W, Chen Y, Huang J et al. Systemic immune-inflammation index predicts the clinical outcome in patients with nasopharyngeal carcinoma: a propensity score-matched analysis. Oncotarget 2017;8(39):66075–66086. doi:10.18632/oncotarget.19796
• 37. Xie QK, Chen P, Hu WM et al. The systemic immune-inflammation index is an independent predictor of survival for metastatic colorectal cancer and its association with the lymphocytic response to the tumor. J. Translational Med.2018;16(1):273. doi:10.1186/s12967-018-1638-9
• 38. Fu H, Zheng J, Cai J, et al. Systemic Immune- Inflammation Index (Sİİ) is Useful to Predict Survival Outcomes in Patients After Liver Transplantation for Hepatocellular Carcinoma within Hangzhou Criteria. Cell Physiol Biochem 2018;47:293-301. doi:10.1159/000489807
• 39. Osterlind K, Hansen HH, Hansen M et al. Long-term disease-free survival in small cell carcinoma of the lung: a study of clinical determinants. J Clin Oncol 1986; 4:1307-13.
• 40. Cohen MH, Makuch R, Johnston-Early A, et al. Laboratory parameters as an alternative to performance status in prognostic stratification of patients with small cell lung cancer. Cancer Treat Rep 1981; 65:187-195.
• 41. Osterlind K, Anderson PK: Prognostic factors in small cell lung cancer: Multivariate model based on 778 patients with chemotherapy with or without irradiation. Cancer Res 1986; 46:4189-94.
• 42. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol2017;18:1116-25. doi:10.1016/S1470-2045(17)30318-2
• 43. Hu K, Lou L, Ye J, Zhang S. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open. 2015;5(4): e006404. doi:10.1136/bmjopen-2014-006404
• 44. Laguna MP. Re: change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. J. Urol. 2016;196(6):1634–1635. doi.10.1016/j.juro.2016.09.042
• 45. Hong X, Cui B, Wang M, Yang Z, Wang L, Xu Q. Systemic immune-inflammation index, based on platelet counts and neutrophil–lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer. Tohoku J. Exp. Med. 2015;236(4), 297-304. doi:10.1620/tjem.236.297
• 46. Wang D, Guo D, Shi F, et al. The predictive effect of the systemic immune-inflammation index for patients with small-cell lung cancer. Future Oncol 2019;15(29):3367–3379. doi:10.2217/fon-2019-0288
• 47. Dolan RD, McSorley ST, Horgan PG, et al. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis. Crit Rev Oncol Hematol 2017; 116:134-46. doi:10.1016/j.critrevonc.2017.06.002
• 48. Dvorak HF. Tumor Stroma, Tumor Blood Vessels, and Antiangiogenesis Therapy. Cancer J 2015; 21:237-43. doi: 10.1097/PPO.0000000000000124
• 49. Tecchio C, Scapini P, Pizzolo G, Cassatella MA. On the cytokines produced by human neutrophils in tumors. Semin. Cancer Biol. 2013;23(3):159–170. doi:10.1016/j.semcancer.2013.02.004
• 50. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause of human cancer. J. Intern. Med. 2000;248(3):171–183. doi:10.1046/j.1365-2796.2001.00742.x
• 51. Sica A, Allavena P, Mantovani A. Cancer related inflammation: the macrophage connection. Cancer Lett. 2008;267(2):204–215. doi:10.1016/j.canlet.2008.03.028
• 52. Muller I, Munder M, Kropf P, Hansch GM. Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol. 2009;30(11):522–530. doi:10.1016/j.it.2009.07.007
• 53. Li N. Platelets in cancer metastasis: To help the "villain" to do evil. Int J Cancer 2016;138:2078-87. doi:10.1002/ijc.29847
• 54. Cristina F, Glenn D. Dual roles for immunity in gastrointestinal cancers. J. Clin. Oncol. 2010; 28(26):4045–4051. doi:10.1200/jco.2010.27.9992
• 55. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144(5):646–674. doi.10.1016/j.cell.2011.02.013
• 56. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6): dju124.doi:10.1093/jnci/dju124
• 57. Aziz MH, Sideras K, Aziz NA et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann. Surg. 2019.270(1):139-146. doi:10.1097/sla.0000000000002660