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Impact of Prolonged Fraction Delivery Time Modelling Stereotactic Body Radiation Therapy with High Dose Hypofractionation on the Killing of Cultured ACHN Renal Cell Carcinoma Cell Line

Document Type : Original Research

Authors

1 Department of Medical Physics, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran

2 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Medical Physics and Medical Engineering, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Radiation Oncology, Milad Hospital, Isfahan, Iran

Abstract

Introduction: Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose per fraction through complex treatment techniques. The increased complexity leads to longer dose delivery times for each fraction. The purpose of this study is to investigate the impact of prolonged fraction delivery time with high-dose hypofractionation on the killing of cultured ACHN cells.Methods and Materials: The radiobiological characteristics and repair half-time of human ACHN renal cell carcinoma cell line were studied with clonogenic assays. A total dose of 20 Gy was administered in 1, 2 or 3 fractions over 15, 30 or 45 min to investigate the biological effectiveness of radiation delivery time and hypofractionation. Cell cycle and apoptosis analysis was performed after 3-fraction irradiation over 30 and 45 min.Results: The α/β and repair half-time were 5.2 Gy and 19 min, respectively. The surviving fractions increased with increase in the fraction delivery time and decreased more pronouncedly with increase in the fraction number over a treatment period of 30 to 45 min. With increase in the total radiation time to 30 and 45 min, it was found that with the same total dose, 2- and 3-fraction irradiation led to more cell killing than 1-fraction irradiation. 3-fraction radiation induced G2/M arrest, and the percentage of apoptotic cells decreased when the fraction delivery time increased from 30 min to 45 min.Conclusion: Our findings revealed that sublethal damage repair and redistribution of the cell cycle were predominant factors affecting cell response in the prolonged and hypofractionated irradiation regimes, respectively.

Keywords

References
  1. Protzel C, Maruschke M, Hakenberg OW. Epidemiology, aetiology, and pathogenesis of renal cell carcinoma. European Urology Supplements. 2012;11:52-9. doi.org/10.1016/j.eursup.2012.05.002.
  2. Robb VA, Karbowniczek M, Klein-Szanto AJ, Henske EP. Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol. 2007;177:346-52. doi.org/10.1016/j.juro.2006.08.076. PubMed PMID: 17162089.
  3. Yu H, Lin X, Wang F, Zhang B, Wang W, Shi H, et al. Proliferation inhibition and the underlying molecular mechanisms of microRNA-30d in renal carcinoma cells. Oncol Lett. 2014;7:799-804. PubMed PMID: 24520297. PubMed PMCID: 3919943.
  4. Mena AC, Pulido EG, Guillen-Ponce C. Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor: sunitinib. Anticancer Drugs. 2010;21:S3-11. doi.org/10.1097/01.cad.0000361534.44052.c5. PubMed PMID: 20110785.
  5. Kochevar J. Blockage of autonomous growth of ACHN cells by anti-renal cell carcinoma monoclonal antibody 5F4. Cancer Res. 1990;50:2968-72. PubMed PMID: 2334900.
  6. Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, et al. Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol. 2011;6:34. doi.org/10.1186/1748-717X-6-34. PubMed PMID: 21477295. PubMed PMCID: 3094365.
  7. Lo SS, Fakiris AJ, Chang EL, Mayr NA, Wang JZ, Papiez L, et al. Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol. 2010;7:44-54. doi.org/10.1038/nrclinonc.2009.188. PubMed PMID: 19997074.
  8. Wersall PJ, Blomgren H, Lax I, Kalkner KM, Linder C, Lundell G, et al. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol. 2005;77:88-95. doi.org/10.1016/j.radonc.2005.03.022. PubMed PMID: 15972239.
  9. Svedman C, Sandstrom P, Pisa P, Blomgren H, Lax I, Kalkner KM, et al. A prospective Phase II trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma. Acta Oncol. 2006;45:870-5. doi.org/10.1080/02841860600954875. PubMed PMID: 16982552.
  10. Svedman C, Karlsson K, Rutkowska E, Sandstrom P, Blomgren H, Lax I, et al. Stereotactic body radiotherapy of primary and metastatic renal lesions for patients with only one functioning kidney. Acta Oncol. 2008;47:1578-83. doi.org/10.1080/02841860802123196. PubMed PMID: 18607859.
  11. Teh BS, Ishiyama H, Mathews T, Xu B, Butler EB, Mayr NA, et al. Stereotactic body radiation therapy (SBRT) for genitourinary malignancies. Discov Med. 2010;10:255-62. PubMed PMID: 20875347.
  12. Wang X, Xiong XP, Lu J, Zhu GP, He SQ, Hu CS, et al. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer. Radiat Oncol. 2011;6:4. doi.org/10.1186/1748-717X-6-4. PubMed PMID: 21226899. PubMed PMCID: 3024935.
  13. Benedict SH, Lin PS, Zwicker RD, Huang DT, Schmidt-Ullrich RK. The biological effectiveness of intermittent irradiation as a function of overall treatment time: development of correction factors for linac-based stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 1997;37:765-9. doi.org/10.1016/S0360-3016(97)00023-0. PubMed PMID: 9128949.
  14. Elkind MM. The initial part of the survival curve: does it predict the outcome of fractionated radiotherapy? Radiat Res. 1988;114:425-36. doi.org/10.2307/3577116. PubMed PMID: 3287428.
  15. Elkind MM, Sutton H. X-ray damage and recovery in mammalian cells in culture. Nature. 1959;184:1293-5. doi.org/10.1038/1841293a0. PubMed PMID: 13819951.
  16. Fowler JF, Welsh JS, Howard SP. Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys. 2004;59:242-9. doi.org/10.1016/j.ijrobp.2004.01.004. PubMed PMID: 15093921.
  17. Zheng XK, Chen LH, Wang WJ, Ye F, Liu JB, Li QS, et al. Impact of prolonged fraction delivery times simulating IMRT on cultured nasopharyngeal carcinoma cell killing. Int J Radiat Oncol Biol Phys. 2010;78:1541-7. doi.org/10.1016/j.ijrobp.2010.07.005. PubMed PMID: 21092834.
  18. Wang JZ, Li XA, D’Souza WD, Stewart RD. Impact of prolonged fraction delivery times on tumor control: a note of caution for intensity-modulated radiation therapy (IMRT). Int J Radiat Oncol Biol Phys. 2003;57:543-52. doi.org/10.1016/S0360-3016(03)00499-1. PubMed PMID: 12957268.
  19. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679-94. doi.org/10.1259/0007-1285-62-740-679. PubMed PMID: 2670032.
  20. Sterzing F, Munter MW, Schafer M, Haering P, Rhein B, Thilmann C, et al. Radiobiological investigation of dose-rate effects in intensity-modulated radiation therapy. Strahlenther Onkol. 2005;181:42-8. doi.org/10.1007/s00066-005-1290-1. PubMed PMID: 15660192.
  21. Lin PS, Wu A. Not all 2 Gray radiation prescriptions are equivalent: Cytotoxic effect depends on delivery sequences of partial fractionated doses. Int J Radiat Oncol Biol Phys. 2005;63:536-44. doi.org/10.1016/j.ijrobp.2005.06.010. PubMed PMID: 16168846.
  22. Mu X, Lofroth PO, Karlsson M, Zackrisson B. The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem. Radiother Oncol. 2003;68:181-7. doi.org/10.1016/S0167-8140(03)00165-8. PubMed PMID: 12972314.
  23. Zheng XK, Chen LH, Yan X, Wang HM. Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing. World J Gastroenterol. 2005;11:1452-6. doi.org/10.3748/wjg.v11.i10.1452. PubMed PMID: 15770720. PubMed PMCID: 4305686.
  24. Kothari G, Foroudi F, Gill S, Corcoran NM, Siva S. Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: a systematic review. Acta Oncol. 2015;54:148-57. doi.org/10.3109/0284186X.2014.939298. PubMed PMID: 25140860.
  25. Dale RG. The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol. 1985;58:515-28. doi.org/10.1259/0007-1285-58-690-515. PubMed PMID: 4063711.
  26. Dale RG. Radiobiological assessment of permanent implants using tumour repopulation factors in the linear-quadratic model. Br J Radiol. 1989;62:241-4. doi.org/10.1259/0007-1285-62-735-241. PubMed PMID: 2702381.
  27. Ning S, Trisler K, Wessels BW, Knox SJ. Radiobiologic studies of radioimmunotherapy and external beam radiotherapy in vitro and in vivo in human renal cell carcinoma xenografts. Cancer. 1997;80:2519-28. doi.org/10.1002/(SICI)1097-0142(19971215)80:12+3.0.CO;2-E. PubMed PMID: 9406705.
  28. Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res. 2012;177:311-27. doi.org/10.1667/RR2773.1. PubMed PMID: 22229487.
  29. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15:5379-88. doi.org/10.1158/1078-0432.CCR-09-0265. PubMed PMID: 19706802. PubMed PMCID: 2746048.
  30. Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 2014;88:254-62. doi.org/10.1016/j.ijrobp.2013.07.022. PubMed PMID: 24411596. PubMed PMCID: 3893711.
  31. Withers HR. Cell cycle redistribution as a factor in multifraction irradiation. Radiology. 1975;114:199-202. doi.org/10.1148/114.1.199. PubMed PMID: 1208860.
  32. Yao Q, Zheng R, Xie G, Liao G, Du S, Ren C, et al. Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy. Sci Rep. 2015;5:9119. doi.org/10.1038/srep09119. PubMed PMID: 25766900. PubMed PMCID: 4357857.
Journal of Biomedical Physics and Engineering
Volume 7, Issue 3 - Serial Number 3
25
September and October 2017
Pages 205-216
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