Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지
DOI QR코드

DOI QR Code

Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery

  • Kim, Mi-Sook (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Wonwoo (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Park, In Hwan (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Hee Jong (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Eunjin (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Jung, Jae-Hoon (Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences) ;
  • Cho, Lawrence Chinsoo (Department of Radiation Oncology, University of Minnesota Medical School) ;
  • Song, Chang W. (Department of Radiation Oncology, University of Minnesota Medical School)
  • Received : 2015.11.26
  • Accepted : 2015.12.07
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Despite the increasing use of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS) in recent years, the biological base of these high-dose hypo-fractionated radiotherapy modalities has been elusive. Given that most human tumors contain radioresistant hypoxic tumor cells, the radiobiological principles for the conventional multiple-fractionated radiotherapy cannot account for the high efficacy of SBRT and SRS. Recent emerging evidence strongly indicates that SBRT and SRS not only directly kill tumor cells, but also destroy the tumor vascular beds, thereby deteriorating intratumor microenvironment leading to indirect tumor cell death. Furthermore, indications are that the massive release of tumor antigens from the tumor cells directly and indirectly killed by SBRT and SRS stimulate anti-tumor immunity, thereby suppressing recurrence and metastatic tumor growth. The reoxygenation, repair, repopulation, and redistribution, which are important components in the response of tumors to conventional fractionated radiotherapy, play relatively little role in SBRT and SRS. The linear-quadratic model, which accounts for only direct cell death has been suggested to overestimate the cell death by high dose per fraction irradiation. However, the model may in some clinical cases incidentally do not overestimate total cell death because high-dose irradiation causes additional cell death through indirect mechanisms. For the improvement of the efficacy of SBRT and SRS, further investigation is warranted to gain detailed insights into the mechanisms underlying the SBRT and SRS.

Keywords

References

  1. Jang WI, 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. https://doi.org/10.1186/1748-717X-8-250
  2. Nagata Y. Stereotactic body radiotherapy for early stage lung cancer. Cancer Res Treat 2013;45:155-61. https://doi.org/10.4143/crt.2013.45.3.155
  3. Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-6. https://doi.org/10.1001/jama.2010.261
  4. Cho LC, Fonteyne V, DeNeve W, Lo SS, Timmerman RD. Stereotactic body radiotherapy. In: Levitt SH, Purdy JA, Perez CA, Poortmans P, editors. Technical basis of radiation therapy: practical clinical applications. 5th ed. New York, NY: Springer; 2012. p. 363-400.
  5. Staehler M, Bader M, Schlenker B, et al. Single fraction radiosurgery for the treatment of renal tumors. J Urol 2015; 193:771-5. https://doi.org/10.1016/j.juro.2014.08.044
  6. Kim YJ, Cho KH, Kim JY, et al. Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol Biol Phys 2011;81:483-9. https://doi.org/10.1016/j.ijrobp.2010.05.033
  7. Song CW, Park H, Griffin RJ, Levitt SH. Radiobiology of stereotactic radiosurgery and stereotactic body radiation therapy. In: Levitt SH, Purdy JA, Perez CA, Poortmans P, editors. Technical basis of radiation therapy: practical clinical applications. 5th ed. New York, NY: Springer; 2012. p. 51-61.
  8. Song CW, Kim MS, Cho LC, Dusenbery K, Sperduto PW. Radiobiological basis of SBRT and SRS. Int J Clin Oncol 2014; 19:570-8. https://doi.org/10.1007/s10147-014-0717-z
  9. 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. https://doi.org/10.1016/j.ijrobp.2013.07.022
  10. Song CW, Cho LC, Yuan J, Dusenbery KE, Griffin RJ, Levitt SH. Radiobiology of stereotactic body radiation therapy/ stereotactic radiosurgery and the linear-quadratic model. Int J Radiat Oncol Biol Phys 2013;87:18-9. https://doi.org/10.1016/j.ijrobp.2013.03.013
  11. 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;89:924-5. https://doi.org/10.1016/j.ijrobp.2014.03.043
  12. Sperduto PW, Song CW, Kirkpatrick JP, Glatstein E. A hypothesis: indirect cell death in the radiosurgery era. Int J Radiat Oncol Biol Phys 2015;91:11-3. https://doi.org/10.1016/j.ijrobp.2014.08.355
  13. Song CW, Lee YJ, Griffin RJ, et al. Indirect tumor cell death after high-dose hypofractionated irradiation: implications for stereotactic body radiation therapy and stereotactic radiation surgery. Int J Radiat Oncol Biol Phys 2015;93:166-72. https://doi.org/10.1016/j.ijrobp.2015.05.016
  14. Kocher M, Treuer H, Voges J, Hoevels M, Sturm V, Muller RP. Computer simulation of cytotoxic and vascular effects of radiosurgery in solid and necrotic brain metastases. Radiother Oncol 2000;54:149-56. https://doi.org/10.1016/S0167-8140(99)00168-1
  15. Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiationinduced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res 2012;177:311-27. https://doi.org/10.1667/RR2773.1
  16. Del Monte U. Does the cell number 10(9) still really fit one gram of tumor tissue? Cell Cycle 2009;8:505-6. https://doi.org/10.4161/cc.8.3.7608
  17. Clement JJ, Tanaka N, Song CW. Tumor reoxygenation and postirradiation vascular changes. Radiology 1978;127:799-803. https://doi.org/10.1148/127.3.799
  18. 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. https://doi.org/10.1007/978-3-7091-9371-6_5
  19. Brown JM, Diehn M, Loo BW Jr. Stereotactic ablative radiotherapy should be combined with a hypoxic cell radiosensitizer. Int J Radiat Oncol Biol Phys 2010;78:323-7. https://doi.org/10.1016/j.ijrobp.2010.04.070
  20. Pasqualini R, Arap W, McDonald DM. Probing the structural and molecular diversity of tumor vasculature. Trends Mol Med 2002;8:563-71. https://doi.org/10.1016/S1471-4914(02)02429-2
  21. Song CW, Levitt SH. Quantitative study of vascularity in Walker carcinoma 256. Cancer Res 1971;31:587-9.
  22. 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;1:671-8. https://doi.org/10.1016/0360-3016(76)90149-8
  23. Song CW, Levitt SH. Effect of x irradiation on vascularity of normal tissues and experimental tumor. Radiology 1970;94: 445-7. https://doi.org/10.1148/94.2.445
  24. Song CW, Levitt SH. Vascular changes in Walker 256 carcinoma of rats following X irradiation. Radiology 1971;100:397-407. https://doi.org/10.1148/100.2.397
  25. Wong HH, Song CW, Levitt SH. Early changes in the functional vasculature of Walker carcinoma 256 following irradiation. Radiology 1973;108:429-34. https://doi.org/10.1148/108.2.429
  26. Song CW, Sung JH, Clement JJ, Levitt SH. Vascular changes in neuroblastoma of mice following x-irradiation. Cancer Res 1974;34:2344-50.
  27. Emami B, Ten Haken RK, Nussbaum GH, Hughes WL. Effects of single-dose irradiation in tumor blood flow studied by 15O decay after proton activation in situ. Radiology 1981;141:207-9. https://doi.org/10.1148/radiology.141.1.7291527
  28. Brown SL, Nagaraja TN, Aryal MP, et al. MRI-tracked tumor vascular changes in the hours after single-fraction irradiation. Radiat Res 2015;183:713-21. https://doi.org/10.1667/RR13458.1
  29. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003;300:1155-9. https://doi.org/10.1126/science.1082504
  30. Solesvik OV, Rofstad EK, Brustad T. Vascular changes in a human malignant melanoma xenograft following single-dose irradiation. Radiat Res 1984;98:115-28. https://doi.org/10.2307/3576056
  31. 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;16:443-54. https://doi.org/10.1007/s10456-012-9329-2
  32. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 2010;120:694-705. https://doi.org/10.1172/JCI40283
  33. Chen FH, Chiang CS, Wang CC, et al. Radiotherapy decreases vascular density and causes hypoxia with macrophage aggregation in TRAMP-C1 prostate tumors. Clin Cancer Res 2009;15:1721-9. https://doi.org/10.1158/1078-0432.CCR-08-1471
  34. Cramer W. Experimental observations on the therapeutic action of radium. In: The 10th Scientific Report on Imperial Cancer Research Fund. London: The Fund; 1932. p. 95-123.
  35. Lasnitzki I. A quantitative analysis of the direct and indirect action of X radiation on malignant cells. Br J Radiol 1947;20: 240-7. https://doi.org/10.1259/0007-1285-20-234-240
  36. 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;11:593-627.
  37. Finkelstein SE, Timmerman R, McBride WH, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol 2011;2011:439752.
  38. McBride WH, Schaue D. In situ tumor ablation with radiation therapy: its effect on the tumor microenvironment and antitumor immunity. In: Keisari Y, editor. Tumor ablation: effects on systemic and local anti-tumor immunity and on other tumormicroenvironment interactions. New York, NY: Springer; 2013. p. 109-19.
  39. Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol 2012;2:191.
  40. Ahmed MM, Guha C, Hodge JW, Jaffee E. Immunobiology of radiotherapy: new paradigms. Radiat Res 2014;182:123-5. https://doi.org/10.1667/RR13849.1
  41. Matsumura S, Wang B, Kawashima N, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol 2008;181:3099-107. https://doi.org/10.4049/jimmunol.181.5.3099
  42. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol 2005;174:7516-23. https://doi.org/10.4049/jimmunol.174.12.7516
  43. 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;114:589-95. https://doi.org/10.1182/blood-2009-02-206870
  44. 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;4:137ra74.
  45. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925-31. https://doi.org/10.1056/NEJMoa1112824
  46. Fowler JF, Welsh JS, Howard SP. Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys 2004; 59:242-9. https://doi.org/10.1016/j.ijrobp.2004.01.004
  47. Jeong JH, Park IW, Kang MA, Kim MS, Song CW. Effect of highdose hypofractionated irradiation (SBRT/SRS) on cell cycle progression [abstract]. In: 61th Radiation Research Society Annual Meeting; 2015 Sep 19-22; Weston, FL. Abstract no. PS1-24.
  48. Park H, Lyons JC, Griffin RJ, Lim BU, Song CW. Apoptosis and cell cycle progression in an acidic environment after irradiation. Radiat Res 2000;153:295-304. https://doi.org/10.1667/0033-7587(2000)153[0295:AACCPI]2.0.CO;2
  49. Brenner DJ. The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 2008;18:234-9. https://doi.org/10.1016/j.semradonc.2008.04.004
  50. 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;18:240-3. https://doi.org/10.1016/j.semradonc.2008.04.005

Cited by

  1. Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma vol.11, pp.None, 2015, https://doi.org/10.1186/s13014-016-0597-7
  2. Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis vol.22, pp.30, 2016, https://doi.org/10.3748/wjg.v22.i30.6851
  3. Stereotactic Body Radiotherapy for Oligometastasis : Opportunities for Biology to Guide Clinical Management vol.22, pp.4, 2015, https://doi.org/10.1097/ppo.0000000000000202
  4. Quality assurance for a multicenter Phase II study of stereotactic ablative radiotherapy for hepatocellular carcinoma ≤5 cm: a planning dummy run vol.47, pp.6, 2015, https://doi.org/10.1093/jjco/hyw156
  5. Spine Metastasis Practice Patterns among Korean, Chinese, and Japanese Radiation Oncologists: A Multinational Online Survey Study vol.58, pp.1, 2015, https://doi.org/10.1093/jrr/rrw089
  6. Primary lung sarcoma treated with stereotactic ablative radiotherapy: a case report vol.10, pp.None, 2015, https://doi.org/10.2147/ott.s138595
  7. Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation vol.8, pp.1, 2017, https://doi.org/10.4103/2152-7806.200581
  8. Clinical Outcomes of Salvage Chemoradiotherapy for Locally Recurrent Biliary Tract Cancer vol.103, pp.4, 2015, https://doi.org/10.5301/tj.5000666
  9. Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery vol.42, pp.1, 2015, https://doi.org/10.3171/2016.9.focus16350
  10. Effects of Intratympanic Dexamethasone on High-Dose Radiation Ototoxicity In Vivo vol.38, pp.2, 2015, https://doi.org/10.1097/mao.0000000000001289
  11. Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors vol.35, pp.2, 2015, https://doi.org/10.3857/roj.2017.00024
  12. Role of HIF-1α in response of tumors to a combination of hyperthermia and radiation in vivo vol.34, pp.3, 2015, https://doi.org/10.1080/02656736.2017.1335440
  13. Feasibility of split-course stereotactic ablative radiotherapy for oligometastases vol.48, pp.6, 2018, https://doi.org/10.1093/jjco/hyy062
  14. The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules vol.11, pp.None, 2015, https://doi.org/10.1177/1179064418761639
  15. Radiation therapy-induced metastasis: radiobiology and clinical implications vol.35, pp.4, 2015, https://doi.org/10.1007/s10585-017-9867-5
  16. Vertebral Compression Fracture After Spine Stereotactic Body Radiation Therapy: A Review of the Pathophysiology and Risk Factors vol.83, pp.3, 2015, https://doi.org/10.1093/neuros/nyx493
  17. Radiotherapy is a safe and effective salvage treatment for recurrent cervical cancer vol.151, pp.2, 2018, https://doi.org/10.1016/j.ygyno.2018.08.029
  18. Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6 + cancer cell and macrophage polarization vol.9, pp.1, 2018, https://doi.org/10.1038/s41467-018-07470-w
  19. A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma vol.13, pp.1, 2015, https://doi.org/10.1186/s13014-018-0992-3
  20. From Whole-Brain Radiotherapy to Immunotherapy: A Multidisciplinary Approach for Patients with Brain Metastases from NSCLC vol.2019, pp.None, 2015, https://doi.org/10.1155/2019/3267409
  21. Maximum standardized uptake value at pre-treatment PET in estimating lung cancer progression after stereotactic body radiotherapy vol.37, pp.1, 2019, https://doi.org/10.3857/roj.2019.00010
  22. The Reciprocity between Radiotherapy and Cancer Immunotherapy vol.25, pp.6, 2015, https://doi.org/10.1158/1078-0432.ccr-18-2581
  23. Twice-daily Radiation for Metastatic Malignant Melanoma: A Different Approach Resulting in a Significant Response vol.11, pp.3, 2015, https://doi.org/10.7759/cureus.4161
  24. Neuroimaging and Stereotactic Body Radiation Therapy (SBRT) for Spine Metastasis vol.28, pp.2, 2015, https://doi.org/10.1097/rmr.0000000000000199
  25. Anemia is a poor prognostic factor for stage I non-small cell lung cancer (NSCLC) patients treated with Stereotactic Body Radiation Therapy (SBRT) vol.16, pp.None, 2015, https://doi.org/10.1016/j.ctro.2019.01.003
  26. Comparison of the dose escalation potential for two hypofractionated radiotherapy regimens for locally advanced pancreatic cancer vol.16, pp.None, 2015, https://doi.org/10.1016/j.ctro.2019.03.001
  27. Locally Advanced Pancreatic Cancer: Work-Up, Staging, and Local Intervention Strategies vol.11, pp.7, 2019, https://doi.org/10.3390/cancers11070976
  28. Reoxygenation and Repopulation of Tumor Cells after Ablative Hypofractionated Radiotherapy (SBRT and SRS) in Murine Tumors vol.192, pp.2, 2015, https://doi.org/10.1667/rr15346.1
  29. Moderate versus extreme hypofractionated radiotherapy: a toxicity comparative analysis in low- and favorable intermediate-risk prostate cancer patients vol.145, pp.10, 2019, https://doi.org/10.1007/s00432-019-02983-3
  30. Establishing the Impact of Vascular Damage on Tumor Response to High-Dose Radiation Therapy vol.79, pp.22, 2015, https://doi.org/10.1158/0008-5472.can-19-1323
  31. Long term results of single high dose Stereotactic Body Radiotherapy in the treatment of primary lung tumors vol.9, pp.1, 2015, https://doi.org/10.1038/s41598-019-51900-8
  32. Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation response vol.95, pp.12, 2019, https://doi.org/10.1080/09553002.2019.1665212
  33. Advances in Radiobiology of Stereotactic Ablative Radiotherapy vol.10, pp.None, 2015, https://doi.org/10.3389/fonc.2020.01165
  34. A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy vol.126, pp.2, 2015, https://doi.org/10.1002/cncr.32502
  35. Clinical utilization of radiation therapy in Korea, 2016 vol.61, pp.2, 2015, https://doi.org/10.1093/jrr/rrz095
  36. Optimization of irradiation interval for fractionated stereotactic radiosurgery by a cellular automata model with reoxygenation effects vol.65, pp.8, 2015, https://doi.org/10.1088/1361-6560/ab7974
  37. Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: Current challenges and future directions vol.64, pp.3, 2015, https://doi.org/10.1111/1754-9485.13032
  38. Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol vol.10, pp.9, 2015, https://doi.org/10.1136/bmjopen-2020-038391
  39. Acoustic neuroma presenting as a hypnic headache vol.14, pp.3, 2015, https://doi.org/10.1136/bcr-2020-235830
  40. Brain Metastasis Response to Stereotactic Radio Surgery: A Mathematical Approach vol.9, pp.7, 2015, https://doi.org/10.3390/math9070716
  41. Hypofractionation in Early Stage Non-Small Cell Lung Cancer vol.31, pp.2, 2015, https://doi.org/10.1016/j.semradonc.2020.11.003
  42. First Asian population study of stereotactic body radiation therapy for ventricular arrhythmias vol.11, pp.1, 2015, https://doi.org/10.1038/s41598-021-89857-2
  43. Improved cellular automata model shows that indirect apoptotic cell death due to vascular damage enhances the local control of tumors by single fraction high-dose irradiation vol.8, pp.1, 2022, https://doi.org/10.1088/2057-1976/ac4466