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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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: 279–285
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: 1337–1382
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: 137–143
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: 635–642
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: 265–277
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: 417–423
Bentzen SM (1993) Quantitative clinical radiobiology. Acta Oncol (to be published)
Bentzen SM, Overgaard J (1992) Time-dose relationships in radiotherapy. In: Steel GG (ed) ESTRO book of basic clinical radiobiology. ESTRO, Leuven, pp 47–54
Bentzen SM, Thames HD (1991) Clinical evidence for tumor clonogen regeneration: interpretations of the data. Radiother Oncol 22: 161–166
Bentzen SM, Thames HD (1992) Overall treatment time and tumor control dose for head and neck tumors: the dog leg revisited. Radiother Oncol 25: 143–144
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: 267–274
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: 169–182
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: 1197–1206
Budihna M, Skrk J, Smid L, Furlan L (1980) Tumor cell repopulation in the rest interval of split-course radiation treatment. Strahlentherapie 156: 402–408
Cohen L (1949) Clinical radiation dosage, part II. Br J Radiol 22: 706–713
Cohen L (1971) A cell population kinetic model for fractionated radiation therapy. I. Normal tissues. Radiology 101: 419–427
Dische S, Saunders MI (1989) Continuous, hyperfractionated, accelerated radiotherapy (CHART): an interim report upon late morbidity. Radiother Oncol 16: 65–72
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: 197–203
Ellis F (1969) Dose, time and fractionation: a clinical hypothesis. Clin Radiol 20: 1–7
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: 1604–1608
Fowler JF (1991) The effect of overall treatment time in radiotherapy for localized prostate carcinoma. Int J Radiat Oncol Biol Phys 21: 1097–1098
Fowler JF, Lindstrom M (1992) Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23: 457–467
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: 188–196
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: 273–279
Hendry JH (1992) Treatment acceleration: the relative time factors and dose-response slopes for tumours and normal tissues. Radiother Oncol 25: 308–312
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: 22–27
Hjelm-Hansen M (1980) Laryngeal carcinoma. IV. Analysis of treatment results using the Cohen model. Acta Radiol Oncol 19: 3–12
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: 13–21
Holsti LR, Mantyla M (1988) Split-course versus continuous radiotherapy. Analysis of a randomized trial from 1964 to 1967. Acta Oncol 27: 153–161
Kleineidam M, Dubben HH (1992) Overall treatment time in the radiotherapy of transitional cell cancer of the bladder. Radiother Oncol 23: 270
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: 561–568
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: 925–933
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: 811–815
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: 813–817
Maciejewski B, Majewski S (1991) Dose fractionation and tumour repopulation in radiotherapy for bladder cancer. Radiother Oncol 21: 163–170
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: 321–328
Marks LB (1992) Treatment time in bladder cancer. Radiother Oncol 23: 269–270
Meinert CL, Tonascia S (1986) Clinical trials. Oxford University Press, New York, pp 71–89
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: 275–281
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: 147–152
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: 13–20
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: 1645–1652
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: 649–658
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: 29–30
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. 114–116
Sambrook DK (1962) Clinical trial of a modified (“split- course”) technique of x-ray therapy in malignant tumors. Clinical Radiology 13: 1–18
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: 215–220
Strandqvist M (1944) Studien über die kumulative Wirkung der Röntgenstrahlen bei Fraktionierung. Acta Radiol 55 [Suppl]: 1–300
Taylor JMG, Kim DK (1989) The poor statistical properties of the Fe-plot. Int J Radiat Biol 56: 161–167
Taylor JMG, Withers HR, Mendenhall WM (1990) Dose-time considerations of head and neck squamous cell carcinomas treated with irradiation. Radiother Oncol 17: 95–102
Taylor JMG, Mendenhall WM, Lavey RS (1991) Time-dose factors in positive neck nodes treated with irradiation only. Radiother Oncol 22: 167–173
Thames HD, Bentzen SM, Turesson I, Overgaard M, van den Bogaert W (1990) Time-dose factors in radiotherapy. Radiother Oncol 19: 219–235
Wang CC (1988) Local control of oropharyngeal carcinoma after two accelerated hyperfractionation radiation therapy schemes. Int J Radiat Oncol Biol Phys 14: 1143–1146
Wheldon TE, Barrett A (1990) Radiobiological rationale for compensation for gaps in radiotherapy regimes by post- gap acceleration of fractionation. Br J Radiol 63: 114–119
Withers HR, Taylor JMG, Maciejewski B (1988) The hazard of accelerated tumor donogen repopulation during radiotherapy. Acta Oncol 27: 131–146
Zagars GK, Schultheiss TE, Peters LJ (1987) Inter-tumor heterogeneity and radiation dose-control curves. Radiother Oncol 8: 353–362
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Bentze, S.M. (1993). Time-Dose Relationships for Human Tumors: Estimation from Nonrandomized Studies. In: Beck-Bornholdt, HP. (eds) Current Topics in Clinical Radiobiology of Tumors. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84918-3_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-84918-3_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-84920-6
Online ISBN: 978-3-642-84918-3
eBook Packages: Springer Book Archive