Skip to main content
SpringerLink
Log in

Radiobiology of Radiosurgery and Hypofractionated Treatments

  • Chapter
  • First Online:
CyberKnife NeuroRadiosurgery

  • 716 Accesses

Abstract

Stereotactic radiosurgery (SRS) has gained a major role in the treatment of brain tumors. This is based on its ability to precisely and accurately deliver a high dose of radiations to a target, thus effectively ablating all viable tumors while minimizing dose and preventing damage in surrounding normal tissue. Although an increasing number of cancer patients have been treated with hypofractionated stereotactic radiotherapy and radiosurgery in recent years, the biological mechanisms of these new modalities have not been fully elucidated. Furthermore, it appears that different biological mechanisms are involved in radiotherapy treatments using different fractionation schemes. The role of 4Rs and the LQ model appears, therefore, limited in stereotactic body radiation therapy (SBRT) and SRS. A simple calculation based on the radiobiological principles for the conventional multi-fractionated radiotherapy clearly suggests that tumor cell death caused by DNA damages by direct effect of radiation alone cannot account for the high efficacy of SBRT and SRS. Evidence now indicates that SBRT and SRS with doses higher than about 10 Gy per fraction induce severe vascular damages in tumors, which then cause secondary and additional tumor cell death. The ensuing degradation of tumor cells would then release massive tumor-specific antigens, thereby elevating antitumor immune response leading to suppression of recurrence of tumors and metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kirkpatrick JP, Soltys SG, Lo SS, Beal K, Shrieve DC, Brown PD. The radiosurgery fractionation quandary: single fraction or hypofractionation? Neuro-Oncology. 2017;19(Suppl_2):ii38–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol. 2015;1(9):1325–32.

    Article  PubMed  Google Scholar 

  3. 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(3):311–27.

    Article  CAS  PubMed  Google Scholar 

  4. Demaria S, Formenti SC. Radiation as an immunological adjuvant: current evidence on dose and fractionation. Front Oncol. 2012;2:153.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Balagamwala E, Chao ABST, Suh JH. Principles of radiobiology of stereotactic radiosurgery and Clinical applications in the central nervous system. Technol Cancer Res Treat. 2012;11:3–13.

    Article  CAS  PubMed  Google Scholar 

  6. MS LLGM, MD JET. Clinical radiation oncology. Churchill Livingstone; 2006.

    Google Scholar 

  7. Mehta MP, Tsao MN, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, Mills M, Rogers CL, Souhami L. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;63:37–46.

    Article  PubMed  Google Scholar 

  8. Hall E. Radiobiology for the radiologist. Philadelphia: Lippincott Williams & Wilkins; 2006.

    Google Scholar 

  9. Cho J, Kodym R, Seliounine S, Richardson JA, Solberg TD, Story MD. High dose-per-fraction irradiation of limited lung volumes using an image-guided, highly focused irradiator: simulating stereotactic body radiotherapy regimens in a small-animal model. Int J Radiat Oncol Biol Phys. 2010;77:895–902.

    Article  PubMed  Google Scholar 

  10. Kondziolka D, Shin SM, Brunswick A, Kim I, Silverman JS. The biology of radiosurgery and its clinical applications for brain tumors. Neuro-Oncology. 2015;17(1):29–44.

    Article  CAS  PubMed  Google Scholar 

  11. Prasanna A, Ahmed MM, Mohiuddin M, Norman Coleman C. Exploiting sensitization windows of opportunity in hyper and hypofractionated radiation therapy. J Thorac Dis. 2014;6(4):287–302.

    PubMed  PubMed Central  Google Scholar 

  12. Kim M-S, Kim W, In Hwan Park BA, Hee Jong Kim MS, Eunjin Lee MS, Jung J-H, Cho LC, Song CW. Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery. Radiat Oncol J. 2015;33(4):265–75.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fowler JF, Welsh JS, Howard SP. Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys. 2004;59:242–9.

    Article  PubMed  Google Scholar 

  14. Jeong JH, Park IW, Kang MA, Kim MS, Song CW. Effect of high dose hypofractionated irradiation (SBRT/SRS) on cell cycle progression [abstract]. In: 61th Radiation research society annual meeting, Weston, FL, 19–22 Sep 2015; 2015. Abstract no. PS1–24.

    Google Scholar 

  15. Hanin LG, Zaider M. Cell-survival probability at large doses: an alternative to the linear-quadratic model. Phys Med Biol. 2010;55(16):4687–702.

    Article  CAS  PubMed  Google Scholar 

  16. Thames HD, Withers HR, Peters LJ, Fletcher GH. Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int J Radiat Oncol Biol Phys. 1982;8:219–26.

    Article  PubMed  Google Scholar 

  17. Withers HR. Biologic basis for altered fractionation schemes. Cancer. 1985;55:2086–95.

    Article  CAS  PubMed  Google Scholar 

  18. Santacroce A, Kamp MA, Budach W, et al. Radiobiology of radiosurgery for the central nervous system. Biomed Res Int. 2013;2013:362761.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hall EJ, Brenner DJ. The radiobiology of radiosurgery: rationale for different treatment regimes for AVMs and malignancies. Int J Radiat Oncol Biol Phys. 1993;25(2):381–5.

    Article  CAS  PubMed  Google Scholar 

  20. Steel GG, McMillan TJ, Peacock JH. The 5Rs of radiobiology. Int J Radiat Biol. 1989;56(6):1045–8.

    Article  CAS  PubMed  Google Scholar 

  21. Withers HR. The four R’s of radiotherapy. New York: Academic; 1975.

    Book  Google Scholar 

  22. Guerrero M, Li XA. Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Phys Med Biol. 2004;49(20):4825–35.

    Article  CAS  PubMed  Google Scholar 

  23. 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):234–9.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Park C, Papiez L, Zhang S, Story M, Timmerman RD. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. J Radiat Oncol Biol Phys. 2008;70(3):847–52.

    Article  Google Scholar 

  25. Brown JM, Carlson DJ, Brenner DJ. Dose escalation, not “new biology,” can account for the efficacy of stereotactic body radiation therapy with non-small cell lung cancer. In reply to Rao et al. Int J Radiat Oncol Biol Phys. 2014;89(3):693–4.

    Article  PubMed  Google Scholar 

  26. 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):254–62.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kirkpatrick JP, Brenner DJ, Orton CG. Point/counterpoint. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Med Phys. 2009;36(8):3381–4.

    Article  PubMed  Google Scholar 

  28. Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell. 2005;8(2):89–91.

    Article  CAS  PubMed  Google Scholar 

  29. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003;300(5622):1155–9.

    Article  CAS  PubMed  Google Scholar 

  30. 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):240–3.

    Article  PubMed  Google Scholar 

  31. 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(1):166–72.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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(1):11–3.

    Article  PubMed  Google Scholar 

  33. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative analyses of normal tissue effects in the clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76(Suppl 3):S3–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Vogelbaum MA, Angelov L, Lee SY, Li L, Barnett GH, Suh JH. Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin. J Neurosurg. 2006;104(6):907–12.

    Article  PubMed  Google Scholar 

  35. Kirkpatrick JP, Marks LB, Mayo CS, Lawrence YR, Bhandare N, Ryu S. Estimating normal tissue toxicity in radiosurgery of the CNS: application and limitations of QUANTEC. J Radiosurg SBRT. 2011;1:95–102.

    PubMed  PubMed Central  Google Scholar 

  36. Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010;77(4):996–1001.

    Article  PubMed  Google Scholar 

  37. Rosenthal DI, Glatstein E. We’ve got a treatment, but What’s the 15. Disease? Or a brief history of Hypofractionation and its relationship to stereotactic. Radiosurgery. Oncologist. 1996;1:1–7.

    Article  CAS  PubMed  Google Scholar 

  38. Sharp CD, Jawahar A, Warren AC, Elrod JW, Nanda A, Alexander JS. Gamma knife irradiation increases cerebral endothelial expression of intercellular adhesion molecule 1 and E-selectin. Neurosurgery. 2003;53:154–60. discussion 160–161.

    Article  PubMed  Google Scholar 

  39. Peña LA, Fuks Z, Kolesnick R. Stress-induced apoptosis and the sphingomyelin pathway. Biochem Pharmacol. 1997;53:615–21.

    Article  PubMed  Google Scholar 

  40. Paris F, Fuks Z, Kang A, Capodieci P, Juan G, Ehleiter D, Haimovitz-Friedman A, Cordon-Cardo C, Kolesnick R. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science. 2001;293:293–7.

    Article  CAS  PubMed  Google Scholar 

  41. Ch’ang H-J, Maj JG, Paris F, Xing HR, Zhang J, Truman J-P, Cardon-Cardo C, Haimovitz-Friedman A, Kolesnick R, Fuks Z. ATM regulates target switching to escalating doses of radiation in the intestines. Nat Med. 2005;11:484–90.

    Article  PubMed  CAS  Google Scholar 

  42. Gulbins E, Kolesnick R. Raft ceramide in molecular medicine. Oncogene. 2003;22:7070–7.

    Article  CAS  PubMed  Google Scholar 

  43. Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R. Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science. 2008;322:110–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene. 2003;22:5897–906.

    Article  CAS  PubMed  Google Scholar 

  45. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116:205–19.

    Article  CAS  PubMed  Google Scholar 

  46. Lu T-P, Lai L-C, Lin B-I, Chen L-H, Hsiao T-H, Liber HL, Cook JA, Mitchell JB, Tsai M-H, Chuang EY. Distinct signaling pathways after higher or lower doses of radiation in three closely related human lymphoblast cell lines. Int J Radiat Oncol Biol Phys. 2010;76:212–9.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rotolo JA, Mesicek J, Maj J, Truman J-P, Haimovitz-Friedman A, Kolesnick R, Fuks Z. Regulation of ceramide synthase-mediated crypt epithelium apoptosis by DNA damage repair enzymes. Cancer Res. 2010;70:957–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shareef MM, Cui N, Burikhanov R, et al. Role of tumor necrosis factor alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma. Cancer Res. 2007;67:11811–20.

    Article  CAS  PubMed  Google Scholar 

  49. Sathishkumar S, Boyanovsky B, Karakashian AA, et al. Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: implications for endothelial apoptosis. Cancer Biol Ther. 2005;4:979–86.

    Article  CAS  PubMed  Google Scholar 

  50. Sathishkumar S, Dey S, Meigooni AS, et al. The impact of TNF-alpha induction on therapeutic efficacy following high dose spatially fractionated (GRID) radiation. Technol Cancer Res Treat. 2002;1:141–7.

    Article  CAS  PubMed  Google Scholar 

  51. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.

    Article  CAS  PubMed  Google Scholar 

  53. Schenken LL, Poulakos L, Hagemann RF. Responses of an experimental solid tumour to irradiation: a comparison of modes of fractionation. Br J Cancer. 1975;31:228–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sakamoto K, Sakka M. The effect of bleomycin and its combined effect with radiation on murine squamous carcinoma treated in vivo. Br J Cancer. 1974;30:463–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Thiagarajan A, Yamada Y. Radiobiology and radiotherapy of brain metastases. Clin Exp Metastasis. 2017;34(6–7):411–9.

    Article  PubMed  Google Scholar 

  56. Corre I, Guillonneau M, Paris F. Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity. Int J Mol Sci. 2013;14:22678–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Garcia-Barros M, Lacorazza D, Petrie H, Haimovitz-Friedman A, Cardon-Cardo C, Nimer S, Fuks Z, Kolesnick R. Host acid sphingomyelinase regulates microvascular function not tumor immunity. Cancer Res. 2004;64:8285–91.

    Article  CAS  PubMed  Google Scholar 

  58. Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol. 2012;2:191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Achrol AS, Guzman R, Varga M, Adler JR, Steinberg GK, Chang SD. Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course. Neurosurg Focus. 2009;26(5):E9.

    Article  PubMed  Google Scholar 

  60. Lindqvist M, Steiner L, Blomgren H, Arndt J, Berggren BM. Stereotactic radiation therapy of intracranial arteriovenous malformations. Acta Radiol Suppl. 1986;369:610–3.

    CAS  PubMed  Google Scholar 

  61. Lawton MT, Arnold CM, Kim YJ, Bogarin EA, Stewart CL, Wulfstat AA, et al. Radiation arteriopathy in the transgenic arteriovenous fistula model. Neurosurgery. 2008;62:1129–38.

    Article  PubMed  Google Scholar 

  62. Chang SD, Shuster DL, Steinberg GK, Levy RP, Frankel K. Stereotactic radiosurgery of arteriovenous malformations: pathologic changes in resected tissue. Clin Neuropathol. 1997;16:111–6.

    CAS  PubMed  Google Scholar 

  63. Schneider BF, Eberhard DA, Steiner LE. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg. 1997;87:352–7.

    Article  CAS  PubMed  Google Scholar 

  64. Bitzer M, Topka H. Progressive cerebral occlusive disease after radiation therapy. Stroke. 1995;26:131–6.

    Article  CAS  PubMed  Google Scholar 

  65. Kamiryo T, Lopes MB, Berr SS, Lee KS, Kassell NF, Steiner L. Occlusion of the anterior cerebral artery after gamma knife irradiation in a rat. Acta Neurochir. 1996;138:983–90.

    Article  CAS  PubMed  Google Scholar 

  66. Munter MW, Karger CP, Reith W, Schneider HM, Peschke P, Debus J. Delayed vascular injury after single high-dose irradiation in the rat brain: histologic immunohistochemical, and angiographic studies. Radiology. 1999;212:475–82.

    Article  CAS  PubMed  Google Scholar 

  67. Qi F, Sugihara T, Yamamoto Y, Abe K. Arterial changes following single-dose irradiation. J Reconstr Microsurg. 1998;14:153–9.

    Article  CAS  PubMed  Google Scholar 

  68. Asur RS, Sharma S, Chang CW, et al. Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells. Radiat Res. 2012;177:751–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hashimoto T, Mesa-Tejada R, Quick CM, Bollen AW, Joshi S, Pile-Spellman J, et al. Evidence of increased endothelial cell turnover in brain arteriovenous malformations. Neurosurgery. 2001;49:124–31.

    CAS  PubMed  Google Scholar 

  70. Sharp FR, Xu H, Lit L, Walker W, Pinter J, Apperson M, et al. Genomic profiles of stroke in blood. Stroke. 2007;38:691–3.

    Article  PubMed  Google Scholar 

  71. Chen Y, Fan Y, Poon KY, Achrol AS, Lawton MT, Zhu Y, et al. MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations. Front Biosci. 2006;11:3121–8.

    Article  CAS  PubMed  Google Scholar 

  72. Chen Y, Pawlikowska L, Yao JS, Shen F, Zhai W, Achrol AS, et al. Interleukin-6 involvement in brain arteriovenous malformations. Ann Neurol. 2006;59:72–80.

    Article  CAS  PubMed  Google Scholar 

  73. Chen Y, Zhu W, Bollen AW, Lawton MT, Barbaro NM, Dowd CF, et al. Evidence of inflammatory cell involvement in brain arteriovenous malformations. Neurosurgery. 2008;62:1340–50.

    Article  PubMed  Google Scholar 

  74. Hao Q, Chen Y, Zhu Y, Fan Y, Palmer D, Su H, et al. Neutrophil depletion decreases VEGF-induced focal angiogenesis in the mature mouse brain. J Cereb Blood Flow Metab. 2007;27:1853–60.

    Article  CAS  PubMed  Google Scholar 

  75. Nuki Y, Matsumoto MM, Tsang E, Young WL, van Rooijen N, Kurihara C, et al. Roles of macrophages in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009;29(3):495–503.

    Article  CAS  PubMed  Google Scholar 

  76. Brooks AL, Benjamin SA, McClellan RO. Toxicity of 90Sr-90Y in Chinese hamsters. Radiat Res. 1974;57:471–81.

    Article  CAS  PubMed  Google Scholar 

  77. Kaminski JM, Shinohara E, Summers JB, et al. The controversial abscopal effect. Cancer Treat Rev. 2005;31:159–72.

    Article  CAS  PubMed  Google Scholar 

  78. Lyng FM, Seymour CB, Mothersill C. Early events in the apoptotic cascade initiated in cells treated with medium from the progeny of irradiated cells. Radiat Prot Dosim. 2002;99:169–72.

    Article  CAS  Google Scholar 

  79. Lyng FM, Seymour CB, Mothersill C. Initiation of apoptosis in cells exposed to medium from the progeny of irradiated cells: a possible mechanism for bystander-induced genomic instability? Radiat Res. 2002;157:365–70.

    Article  CAS  PubMed  Google Scholar 

  80. Hall EJ. The bystander effect. Health Phys. 2003;85:31–5.

    Article  CAS  PubMed  Google Scholar 

  81. Hall EJ, Hei TK. Genomic instability and bystander effects induced by high-LET radiation. Oncogene. 2003;22:7034–42.

    Article  CAS  PubMed  Google Scholar 

  82. Goh K, Sumner H. Breaks in normal human chromosomes: are they induced by a transferable substance in the plasma of persons exposed to total-body irradiation? Radiat Res. 1968;35:171–81.

    Article  CAS  PubMed  Google Scholar 

  83. Hollowell JG Jr, Littlefield LG. Chromosome damage induced by plasma of x-rayed patients: an indirect effect of x-ray. Proc Soc Exp Biol Med. 1968;129:240–4.

    Article  PubMed  Google Scholar 

  84. Sharpe HB, Scott D, Dolphin GW. Chromosome aberrations induced in human lymphocytes by x-irradiation in vitro: the effect of culture techniques and blood donors on aberration yield. Mutat Res. 1969;7:453–61.

    Article  CAS  PubMed  Google Scholar 

  85. Faguet GB, Reichard SM, Welter DA. Radiation-induced clastogenic plasma factors. Cancer Genet Cytogenet. 1984;12:73–83.

    Article  CAS  PubMed  Google Scholar 

  86. Ahmed MM, Sells SF, Venkatasubbarao K, et al. Ionizing radiation inducible apoptosis in the absence of p53 linked to transcription factor EGR-1. J Biol Chem. 1997;272:33056–61.

    Article  CAS  PubMed  Google Scholar 

  87. Hallahan DE, Spriggs DR, Beckett MA, et al. Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation. Proc Natl Acad Sci U S A. 1989;86:10104–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hallahan DE, Haimovitz-Friedman A, Kufe DW, et al. The role of cytokines in radiation oncology. Important Adv Oncol. 1993:71–80.

    Google Scholar 

  89. Hallahan DE, Virudachalam S, Sherman ML, et al. Tumor necrosis factor gene expression is mediated by protein kinase C following activation by ionizing radiation. Cancer Res. 1991;51:4565–9.

    CAS  PubMed  Google Scholar 

  90. Unnithan J, Macklis RM. TRAIL induction by radiation in lymphoma patients. Cancer Investig. 2004;22:522–5.

    Article  CAS  Google Scholar 

  91. Asur R, Butterworth KT, Penagaricano JA, et al. High dose bystander effects in spatially fractionated radiation therapy. Cancer Lett. 2015;356(1):52–7.

    Article  CAS  PubMed  Google Scholar 

  92. Peters ME, Shareef MM, Gupta S, et al. Potential utilization of bystander/Abscopal-mediated signal transduction events in the treatment of solid tumors. Curr Signal Transduct Ther. 2007;2:129–43.

    Article  CAS  Google Scholar 

  93. Konoeda K. Therapeutic efficacy of pre-operative radiotherapy on breast carcinoma: in special reference to its abscopal effect on metastatic lymph nodes. Nihon Gan Chiryo Gakkai Shi. 1990;25:1204–14.

    CAS  PubMed  Google Scholar 

  94. Gupta S, Zagurovskaya M, Wu X et al. Spatially fractionated Grid high dose radiation-induced tumor regression in A549 lung adenocarcinoma xenografts: cytokines and ceramide regulators balance in abscopal phenomena. Sylvester Comprehensive Cancer Center. 2014;20.

    Google Scholar 

  95. Camphausen K, Moses MA, Ménard C, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res. 2003;63:1990–3.

    CAS  PubMed  Google Scholar 

  96. Santana P, Peña LA, Haimovitz-Friedman A, et al. Acid sphingomyelinase deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell. 1996;86:189–99.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology A.O.U. “G. Martino”, Cyberknife Centre of Messina, Messina, Italy

    Antonio Pontoriero

Authors
  1. Antonio Pontoriero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Pontoriero .

Editor information

Editors and Affiliations

  1. Associate Professor of Neurosurgery, Alma Mater Studiorum University of Bologna, Bologna, Italy

    Alfredo Conti

  2. Scientific Director, AB Medica, Milano, Italy

    Pantaleo Romanelli

  3. Assistant Professor, Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Evangelos Pantelis

  4. Associate Professor, Department of Radiation Oncology, Stanford University Cancer Center, Stanford, CA, USA

    Scott G. Soltys

  5. Associate Professor, Department of Neurosurgery and Radiosurgery Center, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea (Republic of)

    Young Hyun Cho

  6. Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Michael Lim

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pontoriero, A. (2020). Radiobiology of Radiosurgery and Hypofractionated Treatments. In: Conti, A., Romanelli, P., Pantelis, E., Soltys, S., Cho, Y., Lim, M. (eds) CyberKnife NeuroRadiosurgery . Springer, Cham. https://doi.org/10.1007/978-3-030-50668-1_12

Download citation

Publish with us

Policies and ethics

Search

Navigation