Abstract
Since the dose delivery pattern is different between intensity-modulated radiotherapy (IMRT) and conventional radiation, radiobiological assessment of the physical dose delivered by IMRT is considered necessary. In IMRT, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is universarily observed in vitro. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation; we demonstrated it in murine tumors. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to high-dose-per-fraction intensity-modulated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear–quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies.
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References
Takemoto S, Shibamoto Y, Ayakawa S et al (2012) Treatment and prognosis of patients with late rectal bleeding after intensity-modulated radiation therapy for prostate cancer. Radiat Oncol 7:87
Manabe Y, Shibamoto Y, Sugie C et al (2014) Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer. J Radiat Res 55(3):494–501
Elkind MM, Sutton H (1960) Radiation response of mammalian cells grown in culture. I. Repair of X-ray damage in surviving Chinese hamster cells. Radiat Res 13:556–593
Elkind MM, Sutton-Gilbert H, Moses WB et al (1965) Radiation response of mammalian cells grown in culture. V. Temperature dependence of the repair of X-ray damage in surviving cells (aerobic and hypoxic). Radiat Res 25:359–376
Iuchi T, Hatano K, Narita Y et al (2006) Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT. Int J Radiat Oncol Biol Phys 64:1317–1324
Kim MJ, Yeo SG, Kim ES et al (2013) Intensity-modulated stereotactic body radiotherapy for stage I non-small cell lung cancer. Oncol Lett 5:840–844
Boda-Heggemann J, Mai S, Fleckenstein J et al (2013) Flattening-filter-free intensity modulated breath-hold image-guided SABR (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot. Radiother Oncol 109:505–509
Kirkpatrick JP, Meyer JJ, Marks LB (2008) The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol 18:240–243
Joiner MC, Bentzen SM (2009) Fractionation: the linear-quadratic approach. In: Joiner M, van der Kogel A (eds) Basic clinical radiobiology. Hodder Arnold, London, pp 102–119
Shibamoto Y, Otsuka S, Iwata H, Tomita N et al (2012) Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy: effect of prolonged delivery time and applicability of the linear-quadratic model. J Radiat Res 53:1–9
Shibamoto Y, Ito M, Sugie C et al (2004) Recovery from sublethal damage during intermittent exposures in cultured tumor cells: implications for dose modification in radiosurgery and IMRT. Int J Radiat Oncol Biol Phys 59:1484–1490
Shibamoto Y, Yukawa Y, Tsutsui K et al (1986) Variation in the hypoxic fraction among mouse tumors of different types, sizes, and sites. Jpn J Cancer Res 77:908–915
Shibamoto Y, Streffer C, Fuhrmann C et al (1991) Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay. Radiat Res 128:293–300
Shibamoto Y, Streffer C, Sasai K et al (1992) Radiosensitization efficacy of KU-2285, RP-170 and etanidazole at low radiation doses: assessment by in vitro cytokinesis-block micronucleus assay. Int J Radiat Biol 61:473–478
Ogino H, Shibamoto Y, Sugie C et al (2005) Biological effects of intermittent radiation in cultured tumor cells: influence of fraction number and dose per fraction. J Radiat Res 46:401–406
Sugie C, Shibamoto Y, Ito M et al (2006) The radiobiological effect of intermittent radiation exposure in murine tumors. Int J Radiat Oncol Biol Phys 64:619–624
Tomita N, Shibamoto Y, Ito M et al (2008) Biological effect of intermittent radiation exposure in vivo: recovery from sublethal damage versus reoxygenation. Radiother Oncol 86:369–374
Shibamoto Y, Sasai K, Abe M et al (1987) The radiation response of SCCVII tumor cells in C3H/He mice varies with the irradiation conditions. Radiat Res 109:352–354
Benedict SH, Lin PS, Zwicker RD et al (1997) 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 37:765–769
Mu X, Löfroth PO, Karlsson M et al (2003) The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem. Radiother Oncol 68:181–187
Zheng XK, Chen LH, Wang WJ et al (2010) Impact of prolonged fraction delivery times simulating IMRT on cultured nasopharyngeal carcinoma cell killing. Int J Radiat Oncol Biol Phys 78:1541–1547
Moiseenko V, Banáth JP, Duzenli C et al (2008) Effect of prolonging radiation delivery time on retention of gammaH2AX. Radiat Oncol 3:18
Moiseenko V, Duzenli C, Durand RE et al (2007) In vitro study of cell survival following dynamic MLC intensity-modulated radiation dose delivery. Med Phys 34:1514–1520
Zheng XK, Chen LH, Yan X et al (2005) Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing. World J Gastroenterol 11:1452–1456
Wang X, **ong XP, Lu J et al (2011) 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 6:4
Jiang L, **ong XP, Hu CS et al (2013) In vitro and in vivo studies on radiobiological effects of prolonged fraction delivery time in A549 cells. J Radiat Res 54:230–234
Withers HR, Thames HD Jr, Peters LJ et al (1983) A new isoeffect curve for change in dose per fraction. Radiother Oncol 1:187–191
Wulf J, Baier K, Mueller G et al (2005) Dose-response in stereotactic irradiation of lung tumors. Radiother Oncol 77:83–87
Milano MT, Katz AW, Schell MC et al (2008) Descriptive analysis of oligometastatic lesions treated with curative-intent stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 72:1516–1522
Onishi H, Shirato H, Nagata Y et al (2011) Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: can SBRT be comparable to surgery? Int J Radiat Oncol Biol Phys 81:1352–1358
Takeda A, Sanuki N, Kunieda E et al (2009) Stereotactic body radiotherapy for primary lung cancer at a dose of 50 Gy total in five fractions to the periphery of the planning target volume calculated using a superposition algorithm. Int J Radiat Oncol Biol Phys 73:442–448
Guckenberger M, Klement RJ, Allgaeuer M et al (2013) Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer. Radiother Oncol 109:13–20
Brenner DJ (2008) The linear-quadratic model is an appropriate methodology for determining iso-effective doses at large doses per fraction. Semin Radiat Oncol 18:234–239
Puck TT, Marcus PI (1956) Action of X-rays on mammalian cells. J Exp Med 103:653–666
Garcia LM, Leblanc J, Wilkins D et al (2006) Fitting the linear-quadratic model to detailed data sets for different dose ranges. Phys Med Biol 51:2813–2823
Iwata H, Shibamoto Y, Murata R et al (2009) Estimation of errors associated with use of linear-quadratic formalism for evaluation of biologic equivalence between single and hypofractionated radiation doses: an in vitro study. Int J Radiat Oncol Biol Phys 75:482–488
Shibamoto Y, Kitakabu Y, Murata R et al (1994) Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation. Int J Radiat Oncol Biol Phys 29:583–586
Murata R, Shibamoto Y, Sasai K et al (1996) Reoxygenation after single irradiation in rodent tumors of different types and sizes. Int J Radiat Oncol Biol Phys 34:859–865
Otsuka S, Shibamoto Y, Iwata H et al (2011) Compatibility of the linear-quadratic formalism and biologically effective dose concept to high-dose-per-fraction irradiation in a murine tumor. Int J Radiat Oncol Biol Phys 81:1538–1543
Douglas BG, Fowler JF (1976) The effect of multiple small doses of x rays on skin reactions in the mouse and a basic interpretation. Radiat Res 66:401–426
van der Kogel AJ (1985) Chronic effects of neutrons and charged particles on spinal cord, lung, and rectum. Radiat Res 8(Suppl):S208–S216
Peck JW, Gibbs FA (1994) Mechanical assay of consequential and primary late radiation effects in murine small intestine: alpha/beta analysis. Radiat Res 138:272–281
Fowler JF (1984) Total doses in fractionated radiotherapy – implications of new radiobiological data. Int J Radiat Biol 46:103–120
Fowler JF (1989) The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 62:679–694
Astrahan M (2008) Some implications of linear-quadratic-linear radiation dose-response with regard to hypofractionation. Med Phys 35:4161–4172
Fowler JF, Tomé WA, Fenwick JD et al (2004) A challenge to traditional radiation oncology. Int J Radiat Oncol Biol Phys 60:1241–1256
Borst GR, Ishikawa M, Nijkamp J et al (2010) Radiation pneumonitis after hypofractionated radiotherapy: evaluation of the LQ(L) model and different dose parameters. Int J Radiat Oncol Biol Phys 77:1596–1603
Park C, Papiez L, Zhang S et al (2008) Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys 70:847–852
Guerrero M, Carlone M (2010) Mechanistic formulation of a linear-quadratic-linear (LQL) model: split-dose experiments and exponentially decaying sources. Med Phys 37:4173–4181
Guerrero M, Li XA (2004) Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Phys Med Biol 49:4825–4835
Wang JZ, Huang Z, Lo SS et al (2010) A generalized linear-quadratic model for radiosurgery, stereotactic body radiation therapy, and high-dose rate brachytherapy. Sci Transl Med 2:39ra48
Butts JJ, Katz R (1967) Theory of RBE for heavy ion bombardment of dry enzymes and viruses. Radiat Res 30:855–871
Curtis SB (1986) Lethal and potentially lethal lesions induced by radiation – a unified repair model. Radiat Res 106:252–270
Iwata H, Matsufuji N, Toshito T et al (2013) Compatibility of the repairable-conditionally repairable, multi-target and linear-quadratic models in converting hypofractionated radiation doses to single doses. J Radiat Res 54:367–373
Scott OC (1990) Mathematical models of repopulation and reoxygenation in radiotherapy. Br J Radiol 63:821–823
Nakamura K, Brahme A (1999) Evaluation of fractionation regimen in stereotactic radiotherapy using a mathematical model of repopulation and reoxygenation. Radiat Med 17:219–225
Acknowledgments
This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (20591501, 23591846).
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Shibamoto, Y., Sugie, C., Ogino, H., Tomita, N. (2015). Radiobiology for IMRT. In: Nishimura, Y., Komaki, R. (eds) Intensity-Modulated Radiation Therapy. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55486-8_3
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DOI: https://doi.org/10.1007/978-4-431-55486-8_3
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