Vol 27, No 1 (2022)
Review paper
Published online: 2022-01-20

open access

Page views 5423
Article views/downloads 814
Get Citation

Connect on Social Media

Connect on Social Media

Radiobiology of stereotactic radiotherapy

Monica Mangoni1, Simona Borghesi2, Cynthia Aristei3, Carlotta Becherini1
Rep Pract Oncol Radiother 2022;27(1):57-62.

Abstract

This paper focuses on the radiobiological mechanisms underlying the effects of stereotactic radiotherapy (SRT) which, despite SRT expansion, have not yet been fully elucidated. Some authors postulated that radiobiology principles, as applied to conventional fractionations (5R: reoxygenation, repair, repopulation, redistribution, radioresistence), suffice in themselves to account for the excellent clinical results of SRT; others argued that the role of the 5R was limited. Recent preclinical data showed that hypofractionated ablative treatments altered the microenvironment, thus determining cell death either directly or indirectly. Furthermore, dead tumor cells released quantities of antigens, which stimulated antitumor immunity, thus reducing the risk of relapse and metastasis. Better understanding of the radiobiological mechanisms underlying response to high-dose radiation treatment is essential for predicting its short- and long-term effects on the tumor and surrounding healthy tissues and, consequently, for improving its related therapeutic index.

Article available in PDF format

View PDF Download PDF file

References

  1. 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(2): 254–262.
  2. Song CW, Park H, Griffin RJ. et al. Radiobiology of stereotactic radiosurgery and stereotactic body radiation therapy. In: Levitt SH, Purdy JC, Perez CA, Poortmans P. ed. Technical basis of radiation therapy: practical clinical applications. 5th ed. Springer, New York 2012: 51–61.
  3. Park HJ, Griffin RJ, Hui S, et al. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res. 2012; 177(3): 311–327.
  4. Song CW, Cho LC, Yuan J, et al. Radiobiology of stereotactic body radiation therapy/stereotactic radiosurgery and the linear-quadratic model. Int J Radiat Oncol Biol Phys. 2013; 87(1): 18–19.
  5. Song CW, Park I, Cho LC, et al. Is indirect cell death involved in response of tumors to stereotactic radiosurgery and stereotactic body radiation therapy? Int J Radiat Oncol Biol Phys. 2014; 89(4): 924–925.
  6. McBride WH, Schaue D. In situ tumor ablation with radiation therapy: its effect on the tumor microenvironment and anti-tumor immunity. In: Keisari Y. ed. Tumor ablation: effects on systemic and local anti-tumor immunity and on other tumor-microenvironment interactions. Springer, New York 2013: 109–119.
  7. Finkelstein SE, Timmerman R, McBride WH, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol. 2011; 2011: 439752.
  8. Macià I Garau M. Radiobiology of stereotactic body radiation therapy (SBRT). Rep Pract Oncol Radiother. 2017; 22(2): 86–95.
  9. Song CW, Glatstein E, Marks LB, et al. Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death. Int J Radiat Oncol Biol Phys. 2021; 110(1): 21–34.
  10. Li S, Shen L. Radiobiology of stereotactic ablative radiotherapy (SABR): perspectives of clinical oncologists. J Cancer. 2020; 11(17): 5056–5068.
  11. Qiu B, Aili A, Xue L, et al. Advances in Radiobiology of Stereotactic Ablative Radiotherapy. Front Oncol. 2020; 10: 1165.
  12. Shibamoto Y, Hashizume C, Baba F, et al. Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer: a multicenter study. Cancer. 2012; 118(8): 2078–2084.
  13. Hall EJ. Radiobiology for the Radiologist, 6th edn. Lippincott Williams and Wilkins, Philadelphia 2006.
  14. Story M, Kodym R, Saha D. Exploring the possibility of unique molecular, biological, and tissue effects with hypofractionated radiotherapy. Semin Radiat Oncol. 2008; 18(4): 244–248.
  15. Fowler JF, Welsh JS, Howard SP. Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys. 2004; 59(1): 242–249.
  16. Ling CC, Gerweck LE, Zaider M, et al. Dose-rate effects in external beam radiotherapy redux. Radiother Oncol. 2010; 95(3): 261–268.
  17. Brenner DJ. The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol. 2008; 18(4): 234–239.
  18. Kim MS, Kim W, Park InH, et al. Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery. Radiat Oncol J. 2015; 33(4): 265–275.
  19. Park H, Lyons J, Griffin R, et al. Apoptosis and Cell Cycle Progression in an Acidic Environment after Irradiation. Radiat Res. 2000; 153(3): 295–304.
  20. Kirkpatrick JP, Meyer JJ, Marks LB. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol. 2008; 18(4): 240–243.
  21. Thames HD, Withers HR, Peters LJ, et al. Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int J Radiat Oncol Biol Phys. 1982; 8(2): 219–226.
  22. Tree AC, Khoo VS, van As NJ, et al. Is biochemical relapse-free survival after profoundly hypofractionated radiotherapy consistent with current radiobiological models? Clin Oncol (R Coll Radiol). 2014; 26(4): 216–229.
  23. Park C, Papiez L, Zhang S, et al. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys. 2008; 70(3): 847–852.
  24. Leith JT, Cook S, Chougule P, et al. Intrinsic and extrinsic characteristics of human tumors relevant to radiosurgery: comparative cellular radiosensitivity and hypoxic percentages. Acta Neurochir Suppl. 1994; 62: 18–27.
  25. Brown JM, Koong AC. High-dose single-fraction radiotherapy: exploiting a new biology? Int J Radiat Oncol Biol Phys. 2008; 71(2): 324–325.
  26. Kim YJ, Cho KHo, Kim JY, et al. Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol Biol Phys. 2011; 81(2): 483–489.
  27. Folkert MR, Bilsky MH, Tom AK, et al. Outcomes and toxicity for hypofractionated and single-fraction image-guided stereotactic radiosurgery for sarcomas metastasizing to the spine. Int J Radiat Oncol Biol Phys. 2014; 88(5): 1085–1091.
  28. Jang WIl, Kim MS, Bae SH, et al. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiat Oncol. 2013; 8: 250.
  29. Jaillet C, Morelle W, Slomianny MC, et al. Radiation-induced changes in the glycome of endothelial cells with functional consequences. Sci Rep. 2017; 7(1): 5290.
  30. Cramer W. Experimental observations on the therapeutic action of radium. Tenth Sci Rep Invest Imp Cancer Research Fund. 1932: 95–12229.
  31. Lasnitzki I. A quantitative analysis of the direct and indirect action of X radiation on malignant cells. Br J Radiol. 1947; 20(234): 240–247.
  32. Clement JJ, Tanaka N, Song CW. Tumor reoxygenation and postirradiation vascular changes. Radiology. 1978; 127(3): 799–803.
  33. Clement JJ, Song CW, Levitt SH. Changes in functional vascularity and cell number following x-irradiation of a murine carcinoma. Int J Radiat Oncol Biol Phys. 1976; 1(7-8): 671–678.
  34. Oh ET, Park MT, Song MJ, et al. Radiation-induced angiogenic signaling pathway in endothelial cells obtained from normal and cancer tissue of human breast. Oncogene. 2014; 33(10): 1229–1238.
  35. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003; 300(5622): 1155–1159.
  36. El Kaffas A, Giles A, Czarnota GJ. Dose-dependent response of tumor vasculature to radiation therapy in combination with Sunitinib depicted by three-dimensional high-frequency power Doppler ultrasound. Angiogenesis. 2013; 16(2): 443–454.
  37. Solesvik OV, Rofstad EK, Brustad T. Vascular changes in a human malignant melanoma xenograft following single-dose irradiation. Radiat Res. 1984; 98(1): 115–128.
  38. Kioi M, Vogel H, Schultz G, et al. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010; 120(3): 694–705.
  39. Matsuya Y, Sasaki K, Yoshii Y, et al. Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects. Sci Rep. 2018; 8(1): 4849.
  40. Merwin R, Algire GH, Kaplan HS. Transparent-chamber observations of the response of a transplantable mouse mammary tumor to local roentgen irradiation. J Natl Cancer Inst. 1950; 11(3): 593–627.
  41. Rubin P, Casarett G. Microcirculation of tumors part II: The supervascularized state of irradiated regressing tumors. Clin Radiol. 1966; 17(4): 346–355.
  42. Wong HH, Song CW, Levitt SH. Early changes in the functional vasculature of Walker carcinoma 256 following irradiation. Radiology. 1973; 108(2): 429–434.
  43. Song CW, Levitt SH. Vascular changes in Walker 256 carcinoma of rats following X irradiation. Radiology. 1971; 100(2): 397–407.
  44. Venkatesulu BP, Mahadevan LS, Aliru ML, et al. Radiation-Induced Endothelial Vascular Injury: A Review of Possible Mechanisms. JACC Basic Transl Sci. 2018; 3(4): 563–572.
  45. Carlson DJ, Keall PJ, Loo BW, et al. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia. Int J Radiat Oncol Biol Phys. 2011; 79(4): 1188–1195.
  46. Kirkpatrick JP, Cárdenas-Navia LI, Dewhirst MW. Predicting the effect of temporal variations in PO2 on tumor radiosensitivity. Int J Radiat Oncol Biol Phys. 2004; 59(3): 822–833.
  47. Qian Y, Von Eyben R, Liu Y, et al. F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy. Int J Radiat Oncol Biol Phys. 2018; 102(4): 1183–1192.
  48. Goodman KA, Sneed PK, McDermott MW, et al. Relationship between pattern of enhancement and local control of brain metastases after radiosurgery. Int J Radiat Oncol Biol Phys. 2001; 50(1): 139–146.
  49. Jensen RL, Minshew L, Shrieve AF, et al. Stereotactic radiosurgery and radiotherapy for meningiomas: biomarker predictors of patient outcome and response to therapy. J Radiosurg SBRT. 2012; 2(1): 41–50.
  50. Carvalho Hd, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo). 2018; 73(suppl 1): e557s.
  51. Wang Y, Boerma M, Zhou D. Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases. Radiat Res. 2016; 186(2): 153–161.
  52. Song CW, Levitt SH. Effect of x irradiation on vascularity of normal tissues and experimental tumor. Radiology. 1970; 94(2): 445–447.
  53. Moding EJ, Castle KD, Perez BA, et al. Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy. Sci Transl Med. 2015; 7(278): 278ra34.
  54. Matsumura S, Wang B, Kawashima N, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol. 2008; 181(5): 3099–3107.
  55. Lugade AA, Moran JP, Gerber SA, et al. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005; 174(12): 7516–7523.
  56. Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009; 114(3): 589–595.
  57. Lan J, Li R, Yin LM, et al. Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2018; 101(1): 74–87.
  58. Seung SK, Curti BD, Crittenden M, et al. Phase 1 study of stereotactic body radiotherapy and interleukin-2--tumor and immunological responses. Sci Transl Med. 2012; 4(137): 137ra74.
  59. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012; 366(10): 925–931.
  60. Golden EB, Formenti SC. Is tumor (R)ejection by the immune system the "5th R" of radiobiology? Oncoimmunology. 2014; 3(1): e28133.
  61. Kang J, Demaria S, Formenti S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016; 4: 51.
  62. Gong J, Le TQ, Massarelli E, et al. Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination. J Immunother Cancer. 2018; 6(1): 46.
  63. Serre R, Barlesi F, Muracciole X, et al. Immunologically effective dose: a practical model for immuno-radiotherapy. Oncotarget. 2018; 9(61): 31812–31819.



Reports of Practical Oncology and Radiotherapy