Tom 9, Nr 5 (2024)
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Opublikowany online: 2024-11-15

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Eksport do Mediów Społecznościowych

Eksport do Mediów Społecznościowych

Do malignant tumors need oxygen to survive radiotherapy?

Bogusław Maciejewski1, Rafał Suwiński2
Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory 2024;9(5):360-367.

Streszczenie

The pathological vascular network in malignant tumors is generally irregular and chaotic. Euoxic clonogenic tumor cells (radiosensitive) are gathered around the vessels, which are unevenly distributed within the tumor volume. The results of many clinical studies [mainly on head and neck (H&N) cancers] have convincingly shown that extension of the overall irradiation time (OTT) needs a pronounced increase in the total dose (TD). It was strongly suggested that the results reflect an accelerated clonogens repopulation, which likely neutralizes about 30% of the cell kill effect of each dose fraction, and it potentially increases to even 80% towards the end of conventional irradiation. However so far, this me­chanism’s activity seems to be quantitatively exaggerated, since towards the end of irradiation, residual 101–102 cancer cells likely become hypoxic and highly resistant to 2 Gy fractions. Thus, local hypoxia should likely be considered as a dominant process responsible for clinical failure. Accelerated repopulation of only a few cellular survivors does not seem reliable. The efficacy of various chemical radiosensitizers, bioreductive drugs, and immuno-boosts are presented and discussed. Finally, it becomes clear that conventional 2 Gy fractionated radiotherapy should no longer be consi­dered as an effective regimen to achieve local tumor control of locally advanced cancer higher than 50%. Pronounced improvement of the RT might be expected using an initial conventional dose of 50 Gy given in 25 fractions followed by a boost of 4–5 large dose (hypo) fractions of 5–6 Gy or by local brachytherapy.

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Referencje

  1. THOMLINSON RH, GRAY LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955; 9(4): 539–549.
  2. Denekamp J. Physiological hypoxia and its influence on radiotherapy. in. The biological basic of radiotherapy. II ed. Elsevier Science Publ 1989: 115–134.
  3. Horsman M, Wouters B, Joiner M, et al. The oxygen effect and fractionated radiotherapy. Basic Clinical Radiobiology Fourth Edition. 2012: 207–216.
  4. Overgaard J, Hansen HS, Overgaard M. Importance of overall treatment since for the outcome of radiotherapy in head and neck carcinoma. Experience from the Danish Head and Neck Cancer study. In: Kogelnik JHD, Sedlmayer E. ed. Progress in Radio-Oncology. VI. Monduzzi Edit 1998: 743–752.
  5. Hermens AF, Barendsen GW. Changes of cell proliferation characteristics in a rat rhabdomyosarcoma before and after x-irradiation. Eur J Cancer (1965). 1969; 5(2): 173–189.
  6. Maciejewski B, Withers HR, Taylor JM, et al. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys. 1989; 16(3): 831–843.
  7. Withers HR, Maciejewski B, Tayor JMG. Biology of options in dose fractionation in the Report 19: The Scientific Basis of Modern Radiotherapy. The Nally NY BIR 1989: 27–36.
  8. Maciejewski B, Składowski K. The dose no longer plays a paramount role in radiotherapy (oncology), but time apparently does. Nowotwory. Journal of Oncology. 2022; 72(2): 80–85.
  9. Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988; 27(2): 131–146.
  10. Maciejewski B, Miszczyk L, Tarnawski R, et al. How the game is played--challenge between therapeutic benefit and acute toxicity in fractionated radiotherapy. Front Radiat Ther Oncol. 2002; 37: 174–184.
  11. Withers HR. Biological bases for modifying conventional fractionation regimens in radiotherapy. Strahlentherapie. 1984; 160(11): 670–677.
  12. Maciejewski B, Preuss-Bayer G, Trott KR. The influence of the number of fractions and of overall treatment time on local control and late complication rate in squamous cell carcinoma of the larynx. Int J Radiat Oncol Biol Phys. 1983; 9(3): 321–328.
  13. Trott KR. Tumour stem cells: the biological concept and its application in cancer treatment. Radiother Oncol. 1994; 30(1): 1–5.
  14. Cox JD, Pajak TF, Marcial VA, et al. Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of radiation therapy oncology group protocol 83-13. Int J Radiat Oncol Biol Phys. 1990; 18(3): 515–521.
  15. Bataini JP, Asselain B, Jaulerry C, et al. A multivariate primary tumour control analysis in 465 patients treated by radical radiotherapy for cancer of the tonsillar region: clinical and treatment parameters as prognostic factors. Radiother Oncol. 1989; 14(4): 265–277.
  16. Peters LJ, Goepfert H, Ang KK, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys. 1993; 26(1): 3–11.
  17. Harwood AR, Beale FA, Cummings BJ, et al. Supraglottic laryngeal carcinoma: an analysis of dose-time-volume factors in 410 patients. Int J Radiat Oncol Biol Phys. 1983; 9(3): 311–319.
  18. Suwinski R, Taylor JM, Withers HR. The effect of heterogeneity in tumor cell kinetics on radiation dose-response. An exploratory investigation of a plateau effect. Radiother Oncol. 1999; 50(1): 57–66.
  19. Maciejewski B, Gabryś D, Rembak-Szynkiewicz J, et al. Have innovations in radiotherapy for head and neck cancer improved the curability of the disease? Nowotwory. Journal of Oncology. 2023; 73(5): 286–293.
  20. Thomlinson RH. Measurement and management of carcinoma of the breast. Clin Radiol. 1982; 33(5): 481–493.
  21. Maciejewski B. Dose-response convers and repopulation of neck lymph node metastases of squamous cell carcinoma of the supraglottic larynx. Radiother Oncol. 1987; 18: 28–36.
  22. Wall TJ, Peters LJ, Brown BW, et al. Relationship between lymph nodal status and primary tumor control probability in tumors of the supraglottic larynx. Int J Radiat Oncol Biol Phys. 1985; 11(11): 1895–1902.
  23. Peters LJ, Withers HR, Thames HD, et al. Tumor radioresistance in clinical radiotherapy. Int J Radiat Oncol Biol Phys. 1982; 8(1): 101–108.
  24. Wouters B, Koritzinsky M. The tumour microenvironment and cellular hypoxia responses. Basic Clinical Radiobiology Fourth Edition. 2012: 217–232.
  25. Horsman MR, van der Kogel AJ. Therapeutic approaches to tumor hypoxia. Basic Clinical Radiobiology Fourth Edition. 2009: 233–245.
  26. Adams GE, Cooke MS. Electron-affinic sensitization. I. A structural basis for chemical radiosensitizers in bacteria. Int J Radiat Biol Relat Stud Phys Chem Med. 1969; 15(5): 457–471.
  27. Churchill-Davidson I. The Oxygen Effect in Radiotherapy: Historical Review. Front Radiat Ther Oncol. 1968; 1: 1–15.
  28. Dische S. Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy. Radiother Oncol. 1985; 3(2): 97–115.
  29. Overgaard J, Hansen HS, Andersen AP, et al. Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys. 1989; 16(4): 1065–1068.
  30. Overgaard J, Hansen HS, Overgaard M, et al. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol. 1998; 46(2): 135–146.
  31. Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007; 25(26): 4066–4074.
  32. Kaanders JH, Bussink J, van der Kogel AJ. ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol. 2002; 3(12): 728–737.
  33. Wasserman TH, Lee DJ, Cosmatos D, et al. Clinical trials with etanidazole (SR-2508) by the Radiation Therapy Oncology Group (RTOG). Radiother Oncol. 1991; 20 Suppl 1: 129–135.
  34. Brizel DM. Chemical modifiers of radiation response. In: Brizel DM. ed. 5th ed. Perez and Brody: Principles and Practice Radiation Oncology. Walter Kluwer, Lippincott 2008: 611–619.
  35. Dische S. Radiotherapy and anaemia — the clinical experience. Radiother Oncol. 1991; 20: 35–40.
  36. Grau C, Overgaard J. Significance of hemoglobin concentration for treatment outcome. Berlin Springer-Verlag 1998: 101–112.
  37. Flickinger JZ. Stereotactic radiosurgery. In: Perez and Brody Principles and Practice of Radiation Oncology. VII ed. Wolter Kluwer, Lippincott 2019: 414–425.
  38. Antonia SJ, Villegas A, Daniel D, et al. PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20): 1919–1929.