Association between serum cytokine levels and the development of acute radiotoxicity in prostate cancer patients

Katarina Kopčalić

doi:10.5937/mp75-45225

Katarina Kopčalić Univerzitet u Beogradu, Medicinski fakultet, Beograd, Srbija

DOI: https://doi.org/10.5937/mp75-45225

Ključne reči: karcinom prostate, radioterapija, radijaciona toksičnost, citokini

Sažetak

U multidisciplinarnom pristupu u lečenju raka prostate, radioterapija igra važnu ulogu.

Međutim, neki pacijenti sa ovom dijagnozom koji su lečeni radioterapiju mogu razviti ozbiljne neželjene efekte koji utiču na njihov kvalitet života.

Akutna i kasna toksičnost se može manifestovati u donjem gastrointestinalnom (GI) traktu razvijajući toksičnost creva i rektuma i genitourinarnom (GU) traktu izazivajući simptome kao posledicu oštećenja uretre, mokraćne bešike i prostate.

Eskalacija doze zračenja takođe povećava rizik od komplikacija na okolnom zdravom tkivu. Međutim, postoje pacijenti sa zadovoljavajućim dozimetrijskim parametrima koji razvijaju toksičnost zračenja i obrnuto.

Predikcioni modeli koji uzimaju u obzir dodatne parametre za identifikaciju pacijenata koji će verovatno razviti toksičnost mogu biti ključni korak ka personalizovanom pristupu u radioterapiji sa modifikacijom doze zračenja, broja frakcija kao i tehnika zračenja. Primarni cilj je smanjenje morbiditeta i poboljšanje kvaliteta života.

Pokazalo se da su izmene u nivou inflamatornih biomarkera u serumu, kao što su citokini, u pozitivnoj korelaciji sa akutnom gastrointestinalnom i genitourinarnom toksičnošću. Podaci iz literature ukazuju na povezanost brojnih citokina sa pojavom GI i GU toksičnosti. Postoje dokazi da TGF- β 1 služi kao ključni medijator fibroze tako što aktivira fibroblaste za proizvodnju ekstracelularnog matriksa. Prema literaturi, IL-6 se smatra jednim od najvažnijih imunoloških markera za predviđanje RT-indukovane toksičnosti normalnih tkiva. Povećane koncentracije IL-6 u serumu tokom radioterapije su značajno povezane sa višim stepenom akutne genitourinarne toksičnosti.

Može se zaključiti da postoji povezanost između radioterapije, razvoja inflamatornog odgovora i pojave toksičnosti zračenja. Međutim, neophodna su dalja istraživanja u cilju adekvatne stratifikacije pacijenata za razvoj individualizovanog pristupa radioterapiji.

Reference

1. Scott E. Prostate cancer. ScientificWorldJournal. 2011 Apr 5; 11:749-50.

2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209–49.

3. Serbian Cancer Registry. Malignant tumors in Republic of Serbia: 2019. Belgrade: Institute of Public Health of Serbia “Dr Milan Jovanović - Batut”; 2021.

4. Foroudi F, Tyldesley S, Barbera L, Huang J, Mackillop WJ. Evidence-based estimate of appropriate radiotherapy utilization rate for prostate cancer. Int J Radiat Oncol Biol Phys. 2003;55(1):51–63.

5. Koper PC, Stroom JC, van Putten WL, Korevaar GA, Heijmen BJ, Wijnmaalen A et al. Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study. Int J Radiat Oncol Biol Phys. 1999 Mar 1; 43(4):727-34.

6. Fischer-Valuck BW, Rao YJ, Michalski JM. Intensity-modulated radiotherapy for prostate cancer. Transl Androl Urol. 2018 Jun; 7(3):297-307.

7. Higuchi D, Ono T, Kakino R, Aizawa R, Nakayasu N, Ito H et al. Evaluation of internal margins for prostate for step and shoot intensity-modulated radiation therapy and volumetric modulated arc therapy using different margin formulas. J Appl Clin Med Phys. 2022 Sep;23(9):e13707

8. Doležel M, Odrážka K, Vaňásek J, Štuk J, Hlávka A, Vítková M et al. Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Klin Onkol. 2020 Winter; 33(1):49-54.

9. Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Sperling D, Pei X et al. Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012 Sep 1; 84(1):125-9.

10. Abdel-Messeih PL, Nosseir NM, Bakhe OH. Evaluation of inflammatory cytokines and oxidative stress markers in prostate cancer patients undergoing curative radiotherapy. Cent Eur J Immunol. 2017;42(1):68-72. doi: 10.5114/ceji.2017.67319. Epub 2017 May 8.

11. Stenmark MH, Cai XW, Shedden K, Hayman JA, Yuan S, Ritter T et al. Combining physical and biologic parameters to predict radiation-induced lung toxicity in patients with non-small-cell lung cancer treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys. 2012 Oct 1; 84(2):e217-22.

12. Wang K, Tepper JE. Radiation therapy-associated toxicity: Etiology, management, and prevention. CA Cancer J Clin. 2021;71(5):437–54

13. West CM, Barnett GC. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome Med. 2011;3(8):52

14. Berkey FJ. Managing the adverse effects of radiation therapy. Am Fam Physician. 2010 Aug 15; 82(4):381-8, 394.

15. Rattay T, Talbot CJ. Finding the genetic determinants of adverse reactions to radiotherapy. Clin Oncol (R Coll Radiol). 2014 May; 26(5):301-8.

16. Stankovic V, Nikitovic M, Pekmezovic T, Pekmezovic D, Kisic Tepavcevic D, Stefanovic Djuric A et al. Toxicity of the lower gastrointestinal tract and its predictive factors after 72Gy conventionally fractionated 3D conformal radiotherapy of localized prostate cancer. J BUON. 2016 Sept-Oct; 21(5):1224-1232.

17. Michalski JM, Winter K, Purdy JA, Parliament M, Wong H, Perez CA et al. Toxicity after three-dimensional radiotherapy for prostate cancer on RTOG 9406 dose Level V. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):706-13.

18. Cozzarini C, Fiorino C, Da Pozzo LF, Alongi F, Berardi G, Bolognesi A et al. Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients. Int J Radiat Oncol Biol Phys. 2012 Jan 1; 82(1):191-9.

19. Rancati T, Palorini F, Cozzarini C, Fiorino C, Valdagni R. Understanding urinary toxicity after radiotherapy for prostate cancer: first steps forward. Tumori. 2017 Sep 18; 103(5):395-404.

20. Cox JD, Stetz JA, Pajak TF. Toxicity criteria of Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31:1341- 1346.

21. Klusa D, Lohaus F, Furesi G, Rauner M, Benešová M, Krause M et al. Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response. Front Oncol. 2021 Mar 4; 10:627379.

22. Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1; 53(5):1097-105.

23. Jereczek-Fossa BA, Orecchia R. Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for non-metastatic prostate cancer. Radiother Oncol. 2007 Aug; 84(2):197-215.

24. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010 Mar 1; 76(3 Suppl):S10-9.

25. Massi MC, Gasperoni F, Ieva F, Paganoni AM, Zunino P, Manzoni Aet al. A Deep Learning Approach Validates Genetic Risk Factors for Late Toxicity After Prostate Cancer Radiotherapy in a REQUITE Multi-National Cohort. Front Oncol. 2020; 10:541281.

26. Peach MS, Showalter TN, Ohri N. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer. Prostate Cancer. 2015; 2015:624736.

27. Penson DF. Quality of life after therapy for localized prostate cancer. Cancer J. 2007;13:318–26

28. Christensen E, Pintilie M, Evans KR, Lenarduzzi M, Ménard C, Catton CN et al. Longitudinal cytokine expression during IMRT for prostate cancer and acute treatment toxicity. Clin Cancer Res. 2009 Sep 1; 15(17):5576-83.

29. Bower JE, Ganz PA, Tao ML, Hu W, Belin TR, Sepah S et al. Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res. 2009 Sep 1; 15(17):5534-40.

30. Kopcalic K, Petrovic N, Stanojkovic TP, Stankovic V, Bukumiric Z, Roganovic J et al. Association between miR-21/146a/155 level changes and acute genitourinary radiotoxicity in prostate cancer patients: A pilot study. Pathol Res Prac.2019 Apr; 215(4): 626-631.

31. Mališić E, Petrović N, Brengues M, Azria D, Matić IZ, Srbljak Ćuk I, Kopčalić K, Stanojković T, Nikitović M. Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer. Sci Rep. 2022 Dec 9; 12(1):21306.

32. Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 1995 Aug 30; 33(1):99-109.

33. Stanojković TP, Matić IZ, Petrović N, Stanković V, Kopčalić K, Besu I et al. Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients. Sci Rep. 2020 Nov 4; 10(1):19002.

34. Tanji N, Kikugawa T, Ochi T, Taguchi S, Sato H, Sato T et al. Circulating Cytokine Levels in Patients with Prostate Cancer: Effects of Neoadjuvant Hormonal Therapy and External-beam Radiotherapy. Anticancer Res. 2015 Jun; 35(6):3379-83.

35. Feng LR, Wolff BS, Lukkahatai N, Espina A, Saligan LN. Exploratory Investigation of Early Biomarkers for Chronic Fatigue in Prostate Cancer Patients Following Radiation Therapy. Cancer Nurs. 2017 May/Jun; 40(3):184-193.

36. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000 May 4; 342(18):1350-8.

37. Peters CA, Stock RG, Cesaretti JA, Atencio DP, Peters S, Burri RJ et al. TGFB1 single nucleotide polymorphisms are associated with adverse quality of life in prostate cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Mar 1; 70(3):752-9.

38. Kopalic K, Matic IZ, Besu I, Stankovic V, Bukumiric Z, Stanojkovic TP et al. Circulating levels of IL-6 and TGF-β1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms. BMC Cancer. 2022 Nov 11; 22 (1):1167.

39. Stankovic V, Džamic Z, Pekmezovic T, Tepavcevic DK, Dozic M, Saric M, Vuckovic S, Nikitovic M. Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters. Clin Oncol (R Coll Radiol). 2016 Sep; 28(9):577-86.

40. Kalff JC, Türler A, Schwarz NT, Schraut WH, Lee KK, Tweardy DJ et al. Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy. Ann Surg. 2003 Mar; 237(3):301-15.

41. Ong ZY, Gibson RJ, Bowen JM, Stringer AM, Darby JM, Logan RM et al. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis. Radiat Oncol. 2010 Mar 16; 5:22.

42. Johnke RM, Edwards JM, Evans MJ, Nangami GN, Bakken NT, Kilburn JM et al. Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression. In Vivo. 2009 Sep-Oct; 23(5):827-33.

43. Okunieff P, Chen Y, Maguire DJ, Huser AK. Molecular markers of radiation-related normal tissue toxicity. Cancer Metastasis Rev. 2008 Sep; 27(3):363-74.

44. Sprung CN, Forrester HB, Siva S, Martin OA. Immunological markers that predict radiation toxicity. Cancer Lett. 2015 Nov 28; 368(2):191-7.

45. Di Maggio FM, Minafra L, Forte GI, Cammarata FP, Lio D, Messa C et al. Portrait of inflammatory response to ionizing radiation treatment. J Inflamm (Lond). 2015 Feb 18; 12:14.

46. Culig Z. Proinflammatory cytokine interleukin-6 in prostate carcinogenesis. Am J Clin Exp Urol. 2014 Oct 2; 2(3):231-8.

47. Tazaki E, Shimizu N, Tanaka R, Yoshizumi M, Kamma H, Imoto S et al. Serum cytokine profiles in patients with prostate carcinoma. Exp Ther Med. 2011 Sep;2(5):887-891

48. Wu CT, Chen MF, Chen WC, Hsieh CC. The role of IL-6 in the radiation response of prostate cancer. Radiat Oncol. 2013 Jun 27; 8:159.

Veza između nivoa citokina u serumu i razvoja akutne radijacione toksičnosti kod pacijenata sa karcinomom prostate

Sažetak

Reference