Glioma pp 179-188 | Cite as

Clinical Implications of Radiobiological Studies on CNS Tolerance

  • A. J. van der Kogel
Conference paper

Abstract

The radiation tolerance of the central nervous system (CNS) has been the subject of many clinical and experimental studies. Because of the radioresistance of high grade gliomas there has been a continuous search for ways to increase the dose on substantial volumes of brain tissue without a concomitant increase in necrosis, although a small risk of complications is considered acceptable. This situation is in contrast to that of the spinal cord, which is rarely the primary target but which is often inevitably an object of radiation directed at paravertebral tumors. Necrosis of the spinal cord is such a devastating complication that its “tolerance” is usually set at a dose level associated with an extremely small risk of late complications. This difference in clinical terms of reference is one of the main reasons for the erroneous assumption of at least a 10 Gy difference in tolerance dose (at 2 Gy per fraction) for brain and spinal cord. This dogma has been strengthened by the formal publication of 5% complication doses (TD5) as being 50 Gy for spinal cord and 60 Gy for brain (Rubin and Casarett 1972). Because the latency of CNS complications is mostly in the range of 1–2 years or even longer, it is difficult to obtain reliable estimates of the incidence of radiation encephalopathies or myelopathies. Nevertheless, it is of interest to note that from a few studies reporting the incidence of myelopathies, a 0–5% incidence dose of approximately 60 Gy can be derived by probit analysis (Fig. 1), which is similar to figures reported for brain (Sheline et al. 1980). In Fig. 1 the incidence of myelopathy in monkey spinal cord is also presented (Schultheiss et al. 1990), which clearly supports the human data while also stressing the relevance of this animal model.

Keywords

Migration Fractionation Oncol Myelitis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbatuci JS, Delozier T, Quint R, Roussel A, Brune D (1978) Radiation myelopathy of the cervical spinal cord: time, dose and volume factors. Int J Radiat Oncol Biol Phys 4: 239–248CrossRefGoogle Scholar
  2. Ang KK, van der Kogel AJ, van Dam J, van der Schueren E (1984) The kinetics of repair of sublethal damage in the rat cervical spinal cord during fractionated irradiations. Radiother Oncol 1: 247–253PubMedCrossRefGoogle Scholar
  3. Ang KK, Thames HD Jr, van der Kogel AJ, van der Schueren E (1987) Is the rate of repair of radiation-induced sublethal damage in rat spinal cord dependent on the size of the dose per fraction? Int J Radiat Oncol Biol Phys 13: 552–562Google Scholar
  4. Ang KK, Jiang GL, Thames HD, Stephens LC (1990) Repair kinetics in rat spinal cord (Abstract). In: Proceedings of the 38th Annual Meeting of the Radiation Research Society, New Orleans, p 113Google Scholar
  5. Barendsen GW (1982) Dose-fractionation, dose-rate and iso-effect relationships for normal tissue response. Int J Radiat Oncol Biol Phys 8: 1981–1997PubMedCrossRefGoogle Scholar
  6. Dische S, Saunders MI (1989) Continuous, hyperfractionated, accelerated radiotherapy (CHART): an interim report upon late morbidity. Radiother Oncol 16: 65–72PubMedCrossRefGoogle Scholar
  7. Dische S, Warburton MF, Saunders MI (1988) Radiation myelitis and survival in the radiotherapy of lung cancer. Int J Radiat Oncol Biol Phys 15: 75–81PubMedGoogle Scholar
  8. Eichhorn HJ, Lessel A, Rotte KH (1972) Einfluß verschiedener Bestrahlungsrhythmen auf Tumor und Normalgewebe in vivo. Strahlenther 143: 614–629Google Scholar
  9. Ellis F (1968) The relationship of biological effect to dose-time-fractionation factors in radiotherapy. Curr Top Radiat Res Quart 4: 357–397Google Scholar
  10. Hopewell JW, van der Kogel AJ (1988) Volume effect in spinal cord. Br J Radiol 61: 973–975CrossRefGoogle Scholar
  11. Hopewell JW, van den Aardweg GJMJ (1988) Current concepts of dose-fractionation in radiotherapy: normal tissue tolerance. Brit J Radiol Supp122: 88–94Google Scholar
  12. Hopewell JW, Morris AD, Dixon-Brown A (1987) The influence of field size on the late tolerance of the rat spinal cord to single doses of X rays. Br J Radio! 60: 1099–1108CrossRefGoogle Scholar
  13. Hornsey S, White A (1980) Isoeffect curve for radiation myelopathy. Br J Radiol 53: 168–169PubMedCrossRefGoogle Scholar
  14. Leibel S, Sheline GE (1987) Tolerance of the central and peripheral nervous system to therapeutic irradiation. In: Lett J (ed) Adv Radiat Biol, vol 12. Academic Press, New York, pp 257–288Google Scholar
  15. Leith JT, DeWyngaert JK, Glicksman AS (1981) Radiation myelopathy in the rat: an interpretation of dose effect relationships. Int J Radiat Oncol Biol Phys 7: 1673–1677PubMedCrossRefGoogle Scholar
  16. Masuda K, Reid BO, Withers HR (1977) Dose effect relationship for epilation and late effects on spinal cord in rats exposed to gamma rays. Radiology 122: 239–242PubMedGoogle Scholar
  17. McCunniff AJ, Liang MJ (1989) Radiation tolerance of the cervical spinal cord. Int J Radiat Oncol Biol Phys 16: 675–678PubMedCrossRefGoogle Scholar
  18. Phillips TL, Buschke F (1969) Radiation tolerance of the thoracic spinal cord. Am J Roentgenol 105: 659–664Google Scholar
  19. Reinhold HS, Kaalen JGAH, Unger-Gils K (1976) Radiation myelopathy of the thoracic spinal cord. Int J Radiat Oncol Biol Phys 1: 651–657PubMedCrossRefGoogle Scholar
  20. Rubin P, Casarett GW (1972) A direction for clinical radiation pathology. The tolerance dose. In: JM Vaeth (ed) Front Radiat Ther Oncol vol 6. Karger and University Park Press, Basel, BaltimoreGoogle Scholar
  21. Scalliet P, Landuyt W, van der Schueren E (1989) Repair kinetics as a determining factor for late tolerance of central nervous system to low dose rate irradiation. Radiother Onco114: 345–353Google Scholar
  22. Schultheiss TE, Orton CG, Peck RA (1983) Models in radiotherapy: Volume effects. Med Phys 10: 410–415Google Scholar
  23. Schultheiss TE, Stephens LC, Jiang GL, Ang KK, Peters LJ (1990) Radiation myelopathy in primates treated with conventional fractionation. Int J Radiat On-col Biol Phys 19: 935–940CrossRefGoogle Scholar
  24. Sheline GE, Wara WM, Smith V (1980) Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 6: 1215–1228PubMedCrossRefGoogle Scholar
  25. Thames HD (1985) An “incomplete-repair” model for survival after fractionated and continuous irradiations. Int J Radiat Biol 47: 319–339CrossRefGoogle Scholar
  26. Thames HD (1989) Repair kinetics in tissues: alternative models. Radiother Oncol 14: 321–327PubMedCrossRefGoogle Scholar
  27. Thames HD, Ang KK, Stewart FA, van der Schueren E (1988) Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction? Int J Radiat Biol 54: 13–19PubMedCrossRefGoogle Scholar
  28. van der Kogel AJ (1977) Radiation tolerance of the rat spinal cord: time-dose relationships. Radiology 122: 505–509PubMedGoogle Scholar
  29. van der Kogel AJ (1979) Late effects of radiation on the spinal cord: dose-effect relationships and pathogenesis. Radiobiological Institute TNO, Rijswijk, pp 1–160Google Scholar
  30. van der Kogel M (1980) Mechanisms of late radiation injury in the spinal cord. In: Meyn RE, Withers HR (eds) Radiation biology in cancer research. Raven Press, New York, pp 461–470Google Scholar
  31. van der Kogel AJ (1983) The cellular basis of radiation induced damage in the CNS. In: Potten CS, Hendry JH (eds) Cytotoxic insult to tissues: effects on cell lineages. Churchill-Livingstone, Edinburgh, pp 329–352Google Scholar
  32. van der Kogel AJ (1987) Effect of volume and localization on rat spinal cord tolerance. In: Fielden EM, Fowler JF, Hendry JH, Scott D (eds) Radiation Research (Proceedings of the 8th International Congress of Radiation Research, vol 1 ) Taylor & Francis: London New York Philadelphia, p 352Google Scholar
  33. van der Kogel M (1989) Continuous, hyperfractionated, accelerated radiotherapy (CHART) (Editorial Comment). Radiother Onco116: 75–77Google Scholar
  34. van der Kogel M (1991) The nervous system: Radiobiology and experimental pathology. In: Scherer E, Streffer C, Trott K-R. (eds) Medical radiology. Diagnostic Imaging and Radiation Oncology, vol “Radiopathology of Organs and Tissues”. Springer, Heidelberg (in the press)Google Scholar
  35. van der Kogel AJ, Sissingh HA (1983) Effect of misonidazole on the tolerance of the rat spinal cord to daily and multiple fractions per day of X rays. Br J Radiol 56: 121–125PubMedCrossRefGoogle Scholar
  36. van der Kogel AJ, Sissingh HA, Zoetelief J (1982) Effect of X rays and neutrons on repair and regeneration in the rat spinal cord. Int J Radiat Oncol Biol Phys 8: 2095–2097PubMedCrossRefGoogle Scholar
  37. van der Schueren E, Landuyt W, Ang KK, van der Kogel AJ (1988) From 2 Gy to 1 Gy per fraction: Sparing effect in rat spinal cord? Int J Radiat Oncol Biol Phys 14: 297–300PubMedCrossRefGoogle Scholar
  38. Wara WM, Phillips TL, Sheline GE, Schwade JG (1975) Radiation tolerance of the spinal cord. Cancer 35: 1558–1562PubMedCrossRefGoogle Scholar
  39. White A, Hornsey S (1980) Time dependent repair of radiation damage in the rat spinal cord after X rays and neutrons. Eur J Cancer 16: 957–962PubMedCrossRefGoogle Scholar
  40. Withers HR, Thames HD Jr, Peters LJ (1983) A new isoeffect curve for change in dose per fraction. Radiother Oncol 1: 187–191PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • A. J. van der Kogel

There are no affiliations available

Personalised recommendations