Advertisement

Time-Dose Relationships for Human Tumors: Estimation from Nonrandomized Studies

  • S. M. Bentze
Part of the Medical Radiology book series (MEDRAD)

Abstract

Tumor cells proliferate before, during, and, unfortunately, in some cases after radiotherapy. With our current radiobiological knowledge, we would expect this fact to result in a reduced probability of local tumor control if the same dose-fractionation schedule were to be applied in a longer overall time. However, independent of any mechanistic considerations at the cellular level, it is a problem for clinical science to decide to what extent an alteration of the treatment time alters the tumor control probability. At first sight this should be a simple task, but a multiple of methodological problems hamper the interpretation of the clinical studies published so far, and the magnitude of the time factor remains controversial at the time of writing. The aim of this chapter is to identify a number of these problems and to review critically our current knowledge of the time factor for human tumors.

Keywords

Treatment Time Local Control Local Control Rate Biological Effective Dose Tumor Control Prob 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amdur RJ, Parsons JT, Mendenhall WM, Million RR, Cassisi NJ (1989) Split-course versus continuous course irradiation in thepost-operative setting of squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 17: 279–285PubMedCrossRefGoogle Scholar
  2. Amdur RJ, Parsons JT, Fitzgerald LT, Million RR (1990) The effect of overall treatment time on local control in patients with adenocarcinoma of the prostate treated with radiation therapy. Int J Radiat Oncol Biol Phys 19: 1337–1382CrossRefGoogle Scholar
  3. Barton MB, Keane TJ, Gadalla T, Maki E (1992) The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer. Radiother Oncol 23: 137–143PubMedCrossRefGoogle Scholar
  4. Bataini JP, Bernier J, Asselain B, Lave C, Jaulerry C, Brunin F, Pontvert D (1988) Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radio- curability of neck nodes. Int J Radiat Oncol Biol Phys 14: 635–642PubMedCrossRefGoogle Scholar
  5. Bataini JP, Asselain B, Jaulerry C, Brunin F, Bernier J, Pontvert D, Lave C (1989) 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 14: 265–277PubMedCrossRefGoogle Scholar
  6. Bentzen SM (1992a) Steepness of the clinical dose-control curve and variation in the in vitro radiosensitivity of head and neck squamous cell carcinoma. Int J Radiat Biol 61: 417–423PubMedCrossRefGoogle Scholar
  7. Bentzen SM (1993) Quantitative clinical radiobiology. Acta Oncol (to be published)Google Scholar
  8. Bentzen SM, Overgaard J (1992) Time-dose relationships in radiotherapy. In: Steel GG (ed) ESTRO book of basic clinical radiobiology. ESTRO, Leuven, pp 47–54Google Scholar
  9. Bentzen SM, Thames HD (1991) Clinical evidence for tumor clonogen regeneration: interpretations of the data. Radiother Oncol 22: 161–166PubMedCrossRefGoogle Scholar
  10. Bentzen SM, Thames HD (1992) Overall treatment time and tumor control dose for head and neck tumors: the dog leg revisited. Radiother Oncol 25: 143–144PubMedCrossRefGoogle Scholar
  11. Bentzen SM, Thames HD, Overgaard M (1989a) Latent-time estimation for late cutaneous and subcutaneous radiation reactions in a single-follow-up clinical study. Radiother Oncol 15: 267–274PubMedCrossRefGoogle Scholar
  12. Bentzen SM, Overgaard J, Thames HD, Overgaard M, Hansen PV, von der Maase H, Meder J (1989b) Clinical radiobiology of malignant melanoma. Radiother Oncol 16: 169–182PubMedCrossRefGoogle Scholar
  13. Bentzen SM, Johansen LV, Overgaard J, Thames HD (1991) Clinical radiobiology of squamous cell carcinoma of the oropharynx. Int J Radiat Oncol Biol Phys 20: 1197–1206PubMedCrossRefGoogle Scholar
  14. Budihna M, Skrk J, Smid L, Furlan L (1980) Tumor cell repopulation in the rest interval of split-course radiation treatment. Strahlentherapie 156: 402–408PubMedGoogle Scholar
  15. Cohen L (1949) Clinical radiation dosage, part II. Br J Radiol 22: 706–713PubMedCrossRefGoogle Scholar
  16. Cohen L (1971) A cell population kinetic model for fractionated radiation therapy. I. Normal tissues. Radiology 101: 419–427PubMedGoogle Scholar
  17. Dische S, Saunders MI (1989) Continuous, hyperfractionated, accelerated radiotherapy (CHART): an interim report upon late morbidity. Radiother Oncol 16: 65–72PubMedCrossRefGoogle Scholar
  18. Edsmyr F, Anderson L, Esposti PL, Littbrand B, Nilsson B (1985) Irradiation with multiple small fractions per day in urinary bladder cancer. Radiother Oncol 4: 197–203PubMedCrossRefGoogle Scholar
  19. Ellis F (1969) Dose, time and fractionation: a clinical hypothesis. Clin Radiol 20: 1–7PubMedCrossRefGoogle Scholar
  20. Feinstein AR, Sosin DM, Wells CK (1985) The Will Rogers phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 312: 1604–1608PubMedCrossRefGoogle Scholar
  21. Fowler JF (1991) The effect of overall treatment time in radiotherapy for localized prostate carcinoma. Int J Radiat Oncol Biol Phys 21: 1097–1098PubMedCrossRefGoogle Scholar
  22. Fowler JF, Lindstrom M (1992) Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23: 457–467PubMedCrossRefGoogle Scholar
  23. Fowler JF, Morgan MA, Silvester JA, Bewley DK, Turner BA (1963) Experiments with fractionated X-ray treatment of the skin of pigs. I. Fractionation up to 28 days. Br J Radiol 36: 188–196PubMedCrossRefGoogle Scholar
  24. Fyles A, Keane TJ, Barton M, Simm J (1992) The effect of overall treatment duration in the local control of cervix cancer. Radiother Oncol 25: 273–279PubMedCrossRefGoogle Scholar
  25. Hendry JH (1992) Treatment acceleration: the relative time factors and dose-response slopes for tumours and normal tissues. Radiother Oncol 25: 308–312PubMedCrossRefGoogle Scholar
  26. Hendry JH, Roberts SA (1991) The sensitivity of human tissues to changes in dose fractionation: deductions from the RCR survey among UK radiotherapists. Clin Oncol 3: 22–27CrossRefGoogle Scholar
  27. Hjelm-Hansen M (1980) Laryngeal carcinoma. IV. Analysis of treatment results using the Cohen model. Acta Radiol Oncol 19: 3–12PubMedCrossRefGoogle Scholar
  28. Hoekstra CJM, Levendag PC, Van Putten WLJ (1990) Squamous cell carcinoma of the supraglottic larynx without clinically detectable lymph node metastases: problem of local relapse and influence of overall treatment time. Int J Radiat Oncol Biol Phys 18: 13–21PubMedCrossRefGoogle Scholar
  29. Holsti LR, Mantyla M (1988) Split-course versus continuous radiotherapy. Analysis of a randomized trial from 1964 to 1967. Acta Oncol 27: 153–161PubMedCrossRefGoogle Scholar
  30. Kleineidam M, Dubben HH (1992) Overall treatment time in the radiotherapy of transitional cell cancer of the bladder. Radiother Oncol 23: 270PubMedCrossRefGoogle Scholar
  31. Lai PP, Perez CA, Shapiro SJ, Lockett MA (1990) Carcinoma of the prostate stage B and C: lack of influence of duration of radiotherapy on tumor control and treatment morbidity. Int J Radiat Oncol Biol Phys 19: 561–568PubMedCrossRefGoogle Scholar
  32. Lai PP, Pilepich MV, Krall JM, Asbell SO, Hanks GE, Perez CA, Rubin P, Sause WT, Cox JD (1991) The effect of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma: the Radiation Therapy Oncology Group 75-06 and 77-06 experience. Int J Radiat Oncol Biol Phys 21: 925–933PubMedCrossRefGoogle Scholar
  33. Lindberg RD, Jones K, Garner HH, Jose B, Spanos WJ Jr, Bhatnagar D (1988) Evaluation of unplanned interruptions in radiotherapy treatment schedules. Int J Radiat Oncol Biol Phys 14: 811–815PubMedCrossRefGoogle Scholar
  34. Lindstrom M, Fowler JF (1991) Re-analysis of the time factor in local control by radiotherapy of T3 T4 squamous cell carcinoma of the larynx. Int J Radiat Oncol Biol Phys 21: 813–817PubMedCrossRefGoogle Scholar
  35. Maciejewski B, Majewski S (1991) Dose fractionation and tumour repopulation in radiotherapy for bladder cancer. Radiother Oncol 21: 163–170PubMedCrossRefGoogle Scholar
  36. Maciejewski B, Preuss-Bayer G, Trott KR (1993) 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 Radit Oncol Phys 9: 321–328Google Scholar
  37. Marks LB (1992) Treatment time in bladder cancer. Radiother Oncol 23: 269–270PubMedCrossRefGoogle Scholar
  38. Meinert CL, Tonascia S (1986) Clinical trials. Oxford University Press, New York, pp 71–89CrossRefGoogle Scholar
  39. Mendenhall WM, Parsons JT, Stringer SP, Cassissi NJ, Million RR (1989) T2 oral tongue carcinoma treated with radiotherapy: analysis of local control and complications. Radiother Oncol 16: 275–281PubMedCrossRefGoogle Scholar
  40. Overgaard J, Hjelm-Hansen M, Johansen LV, Andersen AP (1988) Comparison of conventional and split-course radiotherapy as primary treatment in carcinoma of the larynx. Acta Oncol 27: 147–152PubMedCrossRefGoogle Scholar
  41. Pajak TF, Laramore GE, Marcial VA et al. (1991) Elapsed treatment days—a critical item for radiotherapy quality control review in head and neck trials: RTOG report. Int J Radiat Oncol Biol Phys 20: 13–20PubMedCrossRefGoogle Scholar
  42. Parsons JT, Bova FJ, Million RR (1980) A re-evaluation of split-course technique for squamous cell carcinoma of the head and neck. In J Radiat Oncol Biol Phys 6: 1645–1652Google Scholar
  43. Parsons JT, Mendenhall WM, Cassisi NJ, Isaacs JH, Million RR (1988) Hyper-fractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14: 649–658PubMedCrossRefGoogle Scholar
  44. Parsons JT, Mendenhall WM, Million RR, Cassisi NJ, Stringer SP (1992) Twice-a-day irradiation of squamous cell carcinoma of the head and neck. Sem in Radiat Oncol 2: 29–30CrossRefGoogle Scholar
  45. Pedersen D, Bentzen SM, Overgaard J (1992) Continuous versus split-course brachytherapy and external radiotherapy in locally advanced cervical cancer. In: Mould RF (ed) Brachytherapy in the Nordic Countries. Nucletron, Leersum, pp. 114–116Google Scholar
  46. Sambrook DK (1962) Clinical trial of a modified (“split- course”) technique of x-ray therapy in malignant tumors. Clinical Radiology 13: 1–18PubMedCrossRefGoogle Scholar
  47. Slevin NJ, Hendry JH, Roberts SA, Agren-Cronqvist A (1992) The effect of increasing the treatment time beyond three weeks on the control of T2 and T3 laryngeal cancer using radiotherapy. Radiother Oncol 24: 215–220PubMedCrossRefGoogle Scholar
  48. Strandqvist M (1944) Studien über die kumulative Wirkung der Röntgenstrahlen bei Fraktionierung. Acta Radiol 55 [Suppl]: 1–300Google Scholar
  49. Taylor JMG, Kim DK (1989) The poor statistical properties of the Fe-plot. Int J Radiat Biol 56: 161–167PubMedCrossRefGoogle Scholar
  50. Taylor JMG, Withers HR, Mendenhall WM (1990) Dose-time considerations of head and neck squamous cell carcinomas treated with irradiation. Radiother Oncol 17: 95–102PubMedCrossRefGoogle Scholar
  51. Taylor JMG, Mendenhall WM, Lavey RS (1991) Time-dose factors in positive neck nodes treated with irradiation only. Radiother Oncol 22: 167–173PubMedCrossRefGoogle Scholar
  52. Thames HD, Bentzen SM, Turesson I, Overgaard M, van den Bogaert W (1990) Time-dose factors in radiotherapy. Radiother Oncol 19: 219–235PubMedCrossRefGoogle Scholar
  53. Wang CC (1988) Local control of oropharyngeal carcinoma after two accelerated hyperfractionation radiation therapy schemes. Int J Radiat Oncol Biol Phys 14: 1143–1146PubMedCrossRefGoogle Scholar
  54. Wheldon TE, Barrett A (1990) Radiobiological rationale for compensation for gaps in radiotherapy regimes by post- gap acceleration of fractionation. Br J Radiol 63: 114–119PubMedCrossRefGoogle Scholar
  55. Withers HR, Taylor JMG, Maciejewski B (1988) The hazard of accelerated tumor donogen repopulation during radiotherapy. Acta Oncol 27: 131–146PubMedCrossRefGoogle Scholar
  56. Zagars GK, Schultheiss TE, Peters LJ (1987) Inter-tumor heterogeneity and radiation dose-control curves. Radiother Oncol 8: 353–362PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • S. M. Bentze
    • 1
  1. 1.Department of Experimental Clinical OncologyDanish Cancer SocietyAarhus CDenmark

Personalised recommendations