Radiation oncology: a century of achievements

Abstract

Over the twentieth century the discipline of radiation oncology has developed from an experimental application of X-rays to a highly sophisticated treatment of cancer. Experts from many disciplines — chiefly clinicians, physicists and biologists — have contributed to these advances. Whereas the emphasis in the past was on refining techniques to ensure the accurate delivery of radiation, the future of radiation oncology lies in exploiting the genetics or the microenvironment of the tumour to turn cancer from an acute disease to a chronic disease that can be treated effectively with radiation.

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Figure 1: Wilhelm Conrad Röntgen (1845–1923).
Figure 2: The first illustration of the effect of the duration of Röntgen therapy (now called X-rays) on normal tissues.
Figure 3: Graph to show the therapeutic index with respect to cumulative dose.
Figure 4: Imaging and treatment planning

References

  1. 1

    Grubbé, E. H. Priority in the therapeutic use of X-rays. Radiol. 21, 156–162 (1933).

  2. 2

    Glasser, O. Wilhelm Conrad Röntgen and the Early History of Roentgen Rays (Julius Springer, Berlin, 1931).

  3. 3

    Coolidge, W. D. A powerful roentgen ray tube with a pure electron discharge. Phy. Rev. 2, 409–430 (1913).

  4. 4

    Coliez, R. Les bases physiques de l'irradiation du cancer du col utérin par la curiethérapie et de la radiothérapie combinées. J. Radiol. 7, 201–216 (1923).

  5. 5

    Failla, G. An objective method for the administration of X-rays. Acta Radiol. 4, 85–128 (1925).

  6. 6

    Thoraeus, R. A study of the ionization method for measuring the intensity and absorption of roentgen rays and of the efficiency of different filters used in therapy. Acta Radiol. Suppl. XV (1932).

  7. 7

    Danlos, M. & Bloch, P. Note sur le traitement du lups érythémateux par des applications de radium. Ann. Dermatol. 2, 986 (1901).

  8. 8

    Lysholm, E. Apparatus for the production of a narrow beam of rays in treatment by radium at a distance. Acta Radiol. 2, 516–519 (1923).

  9. 9

    Stentstrom, W. Methods of improving the external application of radium for deep therapy. Am. J. Röntgenol. 11, 176–186 (1924).

  10. 10

    Failla, G. Design of well-protected radium 'pack'. Am. J. Röntgenol. 20, 128–141 (1928).

  11. 11

    Berven, E. The development and organization of therapeutic radiology in Sweden. Radiology 79, 829–841 (1962).

  12. 12

    Paterson, R. & Parker, H. M. A dosage system for γ-ray therapy. Br. J. Radiol. 7, 592–632 (1934).

  13. 13

    Abbe, R. Technical note. Arch Röntgenol. 15, 74 (1910).

  14. 14

    Heyman, J. The Radiumhemmet method of treatmnent and results in cancer of the corpus of the uterus. J. Obstetr. 43, 655 (1936).

  15. 15

    Dubois, J. B. & Ash, D. in Radiation Oncology: A Century of Progress and Achievement: 1895-1995 (ed. Bernier, J.) 79–98 (ESTRO Publication, Brussels, 1995).

  16. 16

    Cleaves, M. A., Radium: with a preliminary note on radium rays in the treatment of cancer. Med. Record. 64, 601–606 (1903).

  17. 17

    Heineke, H. Ueber die Einwirkung der Röntgenstrahlen auf Tiere. Mènch. Med. Wochenschr. 50, 2090–2092 (1903).

  18. 18

    Regaud, C. & Ferroux, R. Discordance des effects de rayons X, d'une part dans le testicile, par le peau, d'autre parts dans le fractionment de la dose. Compt. Rend. Soc. Biol. 97, 431–434 (1927).

  19. 19

    Coutard, H. Principles of X-ray therapy of malignant disease. Lancet 2, 1–12 (1934).

  20. 20

    Baclesse, F. Comparative study of results obtained with conventional radiotherapy (200 KV) and cobalt therapy in the treatment of cancer of the larynx. Clin. Radiol. 18, 292–300 (1967).

  21. 21

    Ellis, F. The relationship of biological effect to dose-time fractionation factors in radiotherapy. Curr. Top. Radiat. Res. 4, 357–397 (1965).

  22. 22

    Bergonié J. & Tribondeau L. L'interprétation de quelques résultats de la radiothérapie et essai de fixation d'une technique rationnelle. C. R. Séances Acad. Sci. 143, 983–985 (1906).

  23. 23

    Petry, E. Zur Kenntnis der Bedingungen der biologischen Wirkung der Rontgenstrahlen. Biochem. Zeitschr. 135, 353 (1923).

  24. 24

    Mottram, J. C. Factor of importance in radiosensitivity of tumours. Brit. J. Radiol. 9, 606–614 (1936).

  25. 25

    Gray, L. H. et al. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br. J. Radiol. 26, 638–648 (1953).

  26. 26

    Thomlinson, R. H. & Gray L. H. Br. J. Cancer 9, 539–549 (1955).

  27. 27

    Trump, J. G. et al. High energy electrons for treatment of extensive superficial malignant lesions. Am. J. Roentgenol. Radium Ther. Nucl. Med. 69, 623–629 (1953).

  28. 28

    Fry, D. W., Harvie, R. B., Mullet L. B. & Walkinshaw, W. Travelling wave linear accelerator for electrons. Nature 160, 351 (1947).

  29. 29

    Fry, D. W. et al. A traveling wave linear accelerator for 4 MeV electrons. Nature 162, 859 (1948).

  30. 30

    Zuppinger, A. & Poretti, G. Symposium on High Energy Electrons (Springer-Verlag, Berlin, 1965).

  31. 31

    Green, D. T. & Errington R. F. Design of a cobalt 60 beam therapy unit. Brit. J. Radiol. 25, 319–323 (1952).

  32. 32

    Johns, H. E., Epp, E. R., Cormack, D. V. & Fedoruk, S. O. 1000 Curie cobalt units for radiation therapy. II. Depth dose data and diaphragm design for the Saskatchewan 1000 curie cobalt unit. Br. J. Radiol. 25, 302–308 (1952).

  33. 33

    Spiers, F. W. & Morrison, M. T. A cobalt 60 unit with a source-skin distance of 20 cm. Br. J. Radiol. 28, 2–7 (1955).

  34. 34

    Lidén, K. A 10-curie Co-60 telegamma unit. Acta Radiol. 38, 139 (1952).

  35. 35

    Lederman, M. & Greatorex, C. A. A Cobalt 60 telecurie unit. Brit. J. Radiol. 26, 525–532 (1953).

  36. 36

    Pierquin, B., Chassagne, D. & Gasiorowski, M. Présentation technique et dosimétrique de curiepuncture par fils d'or-198. J. Radiol. Electrol. Med. Nucl. 40, 690–693 (1959).

  37. 37

    Pierquin, B. & Dutreix, A. For a new methodology in curietherapy: the system of Paris (endo- and plesioradiotherapy with non-radioactive preparation). A preliminary note. Ann. Radiol. 9, 757–760 (1966).

  38. 38

    Puck, T. T. & Marcus P. I. Action of X-rays on mammalian cells. J. Exp. Med. 103, 653–666 (1956).

  39. 39

    Withers, H. R. The dose-survival relationship for irradiation of epithelial cells of mouse skin. Br. J. Radiol. 40, 187–194 (1967).

  40. 40

    Withers, H. R. Regeneration of intestinal mucosa after irradiation. Cancer 28, 75–81 (1971).

  41. 41

    Rockwell, S. C. & Kallman, R. F. Cellular radiosensitivity and tumor radiation response in the EMT6 tumor cell system. Radiat. Res. 53, 281–294 (1973).

  42. 42

    Powers, W. E. & Tolmach, L. J. A multicomponent X-ray survival curve for mouse lymphosarcoma cells irradiated in vivo. Nature 197, 710–711 (1963).

  43. 43

    Hewitt, H. B. & Wilson, C. W. A survival curve for mammalian leukaemia cells irradiated in vivo (implications for the treatment of mouse leukaemia by whole-body irradiation). Br. J. Cancer 13, 69–75 (1959).

  44. 44

    Suit, H. & Wette, R. Radiation dose fractionation and tumour control probability. Radiat. Res. 29, 267–281 (1966).

  45. 45

    Barendsen, G. W. & Broerse, J. J. Experimental radiotherapy of a rat rhabdomyosarcoma with 15 MeV neutrons and 300 kV X-rays. I. Effects of single exposures. Eur. J. Cancer 5, 373–391 (1969).

  46. 46

    Elkind, M. M., Sutton-Gilbert, H., Moses, W. B., Alescio, T. & Swain R. B. Radiation response of mammalian cells in culture: V. Temperature dependence of the repair of X-ray damage in surviving cells (aerobic and hypoxic). Radiat. Res. 25, 359–376 (1965).

  47. 47

    Withers, H. R. in Advances in Radiation Biology Vol. 5 (eds Lett, J. & Adler, H.) 241–271 (Academic Press, New York, 1975).

  48. 48

    Ellis, F. et al. Beam direction in radiotherapy. Symposium. Br. J. Radiol. 16, 31 (1943).

  49. 49

    Cohen, M. & Martin, S. J. Multiple field isodose charts. in Atlas of Radiation Dose Distributions. Vol. II (International Atomic Energy Agency, Vienna, 1966).

  50. 50

    Lauterbeur, P. C. Progress in n.m.r. zeugmatography imaging. Philos. Trans. R. Soc. Lond. B Biol. Sci. 289, 483–487 (1980).

  51. 51

    Mansfield, P. & Maudsley, A. A. Medical imaging by NMR. Br. J. Radiol. 50, 188–194 (1977).

  52. 52

    LoSasso, T. et al. The use of a multi-leaf collimator for conformal radiotherapy of carcinomas of the prostate and nasopharynx. Int. J. Radiat. Oncol. Biol. Phys. 25, 161–170 (1993).

  53. 53

    Burman, C. et al. Planning, delivery, and quality assurance of Intensity-modulated radiotherapy using dynamic multileaf collimator: a strategy for large-scale implementation for the treatment of carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 39, 863–873 (1997).

  54. 54

    Zelefsky, M. J. et al. Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma. Cancer 85, 2460–2468 (1999).

  55. 55

    Fuks, Z., Leibel, S. A. & Ling, C. C. A practical guide to intensity-modulated radiation therapy. Published in cooperation with members of the staff of Memorial Sloan-Kettering Cancer Center. (Medical Physics Publishing, Wisconsin, 2003).

  56. 56

    Blasberg, R. G. & Gelovani, J. Molecular-genetic imaging: a nuclear medicine based perspective. Mol. Imaging 1, 160–180 (2002).

  57. 57

    Ter-Pogossian, M. M., Phelps, M. E., Hoffman, E. J. & Mullani, N. A. A positron-emission transaxial tomograph for nuclear imaging (PETT). Radiology 114, 89–98 (1975).

  58. 58

    Wuthrich, K., Shulman, R. G. & Peisach, J. High-resolution proton magnetic resonance spectra of sperm whale cyanometmyoglobin. Proc. Natl Acad. Sci. USA 60, 373–380 (1968).

  59. 59

    Ling, C. C. et al. Towards multi-dimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int. J. Radiat. Oncol. Biol. Phys. 47, 551–560 (2000).

  60. 60

    Scheidhauer, K. et al. Qualitative [18F]FDG positron emission tomography in primary breast cancer: clinical relevance and practicability. Eur. J. Nucl. Med. 23, 618–623 (1996).

  61. 61

    Rigo, P. et al. Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur. J. Nucl. Med. 23, 1641–1674 (1996).

  62. 62

    Kiffer, J. D. et al. The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer. Lung Cancer 19, 167–177 (1998).

  63. 63

    Shields, A. F. et al. Monitoring tumor response to chemotherapy with [C-11]-thymidine and FDG PET. J. Nucl. Med. 37, 290–296 (1998).

  64. 64

    Shields, A. F. et al. Carbon-11-thymidine and FDG to measure therapy response. J. Nucl. Med. 39, 1757–1762 (1998).

  65. 65

    Rasey, J. S. et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int. J. Radiat. Oncol. Biol. Phys. 36, 417–428 (1996).

  66. 66

    Kurhanewicz, J. et al. Prostate cancer — metabolic response to cryosurgery as detected with 3D H-1 MR spectroscopic imaging. Radiology 200, 489–496 (1996).

  67. 67

    Kurhanewicz, J. et al. Three-dimensional H1 MR spectroscopic imaging of the in situ human prostate with high (0. 24–0.7-cm3) spatial resolution. Radiology 198, 795–805 (1996).

  68. 68

    Zelefsky, M. J. et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int. J. Radiat. Oncol. Biol. Phys. 53, 1111–1116 (2002).

  69. 69

    Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).

  70. 70

    Graeber, T. G. et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379, 88–91 (1996).

  71. 71

    Lowe, S. W., Ruley, H. E., Jacks, T. & Housman, D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957–967 (1993).

  72. 72

    Syllaba, K. & Henner, K. Contribution a l'independence de l'athetose double idiopathique et congenitale. Atteinte familiale, syndrome dystrophique, signe de reseau vasculaire conjonctival, integrite psychique. Rev. Neurol. 1, 541–562 (1926).

  73. 73

    Gotoff, S. P., Amirmokri, E. & Liebner, E. J. Ataxia telangiectasia. Neoplasia, untoward response to X-irradiation, and tuberous sclerosis. Am. J. Dis. Child. 114, 617–625 (1967).

  74. 74

    Taylor, A. M. R. et al. Ataxia-telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 4, 427–429 (1975).

  75. 75

    Bakkenist, C. J. & Kastan, M. B. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421, 499–506 (2003).

  76. 76

    Overgaard, J. & Horsman M. R. Modification of hypoxia induced radioresistance in tumors by the use of oxygen and sensitizers. Semin. Radiat. Oncol. 6, 10–21 (1996).

  77. 77

    Brown, J. M. Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism for reoxygenation. Br. J. Radiol. 52, 650–656 (1979).

  78. 78

    Giaccia, A. J., Siim, B. G. & Johnson, R. J. HIF-1 as a target for drug development. Nature Rev. Drug Discovery 2, 803–811 (2003).

  79. 79

    Folkman, J. in Harrison's Textbook of Internal Medicine 15th edn (eds Braunwald, E. et al.) 517–530 (McGraw-Hill, New York, 2001).

  80. 80

    Garcia-Barros, M. et al. Tumour response to radiotherapy regulated by endothelial cell apoptosis. Science 300, 1155–1159 (2003).

  81. 81

    Thames, H. D., Wither, H. R., Peters L. J. & Fletcher, G. Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int. J. Radiat. Oncol. Biol. Phys. 8, 219–226 (1982).

  82. 82

    Horiot, J. C. et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother. Oncol. 25, 231–241 (1992).

  83. 83

    Fletcher, G. H. in International Advances in Surgical Oncology Vol. 2 (ed. Murphy, G. P.) 55–98 (Alan R. Liss, New York, 1979).

  84. 84

    Leksell, L. Cerebral radiosurgery. I. γ-thalanotomy in two cases of intractable pain. Acta Chir. Scand. 134, 585–595 (1968).

  85. 85

    Larsson, B., Lidén, K. & Sarby, B. Irradiation of small structures through intact skull. Acta Radiol. Ther. 13, 512–534 (1974).

  86. 86

    Pignon, J. P., Bourhis, J., Domenge, C. & Designe, L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 355, 949–955 (2000).

  87. 87

    Freund, L. Grundriss der gesamten Radiotherapie für praktische Årzte. (Urban und Schwarzenberg, Berlin, 1903).

  88. 88

    Coutard, H. Roentgen Therapy of epitheliomas of the tonsillar region, hypopharynx, and larynx from 1920 to 1926. Am. J. Radiol. 3, 313–331 (1932).

  89. 89

    Lagrutta, J., Reggiani, G., Grassi, G. & Raimondi, J. Radiosensitivity and oxygen therapy in gynecologic oncology. Minerva Radiol. 10, 294–295 (1965).

  90. 90

    Zeman, E. M., Brown, J. M., Lemmon, M. J., Hirst, V. K. & Lee W. W. SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int. J. Radiat. Oncol. Biol. Phys. 12, 1239–1242 (1986).

  91. 91

    Stratford, I. J. et al. RSU 1069, a nitroimidazole containing an aziridine group. Bioreduction greatly increases cytotoxicity under hypoxic conditions. Biochem. Pharmacol. 35, 105–109 (1986).

  92. 92

    Savitsky, K. et al. The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum. Mol. Genet. 4, 2025–2032 (1995).

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Correspondence to Jacques Bernier.

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Cancer.gov

breast cancer

cervical cancer

endometrial cancer

head and neck cancer

Entrez Gene

HIF1

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Japanese Society for Therapeutic Radiology and Oncology

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Bernier, J., Hall, E. & Giaccia, A. Radiation oncology: a century of achievements. Nat Rev Cancer 4, 737–747 (2004). https://doi.org/10.1038/nrc1451

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