Abstract
Cure of cancer is defined as locoregional tumor control without distant metastases and without life-threatening treatment complications. Radiotherapy is one of the main cancer treatment modalities. As a local treatment, its aim is to achieve locoregional tumor control by inactivation of all cancer stem cells within the primary tumor and regional lymph nodes. Treatment effects on local tumor control are therefore the focus of this chapter; however, also potential indirect effects on the risk of distant metastases are briefly considered. It is well recognized that the probability to permanently control tumors increases as a sigmoid function with increasing radiation dose. Below a threshold, the dose is not sufficient to inactivate all cancer stem cells in a tumor, i.e. all tumors recur. After this threshold, tumor control increases with increasing radiation dose, approaching 100% at high doses. Even if some data suggest a higher metastatic potential of tumors during radiotherapy, successful radiotherapy is an effective way to stop metastasis at the source, thereby importantly contributing to overall survival of the patient. Inclusion of biological parameters of the individual tumors is anticipated to further improve the results of radiotherapy by tailoring dose and treatment schedule, by combining radiotherapy with modern drugs, and by taking into account intratumoral heterogeneity based on biological imaging.
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References
Allalunis-Turner MJ et al. (1992) Radiosensitivity testing of human primary brain tumor specimens. Int J Radiat Oncol Biol Phys 23(2):339–343
Alsner J, Sorensen SB, Overgaard J (2001) TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. Radiother Oncol 59(2):179–185
Baumann M (2006) Keynote comment: radiotherapy in the age of molecular oncology. Lancet Oncol 7(10):786–787
Baumann M, Petersen C (2005) TCP and NTCP: a basic introduction. Rays 30(2):99–104
Baumann M, Dubois W, Suit HD (1990a) Response of human squamous cell carcinoma xenografts of different sizes to irradiation: relationship of clonogenic cells, cellular radiation sensitivity in vivo, and tumor rescuing units. Radiat Res 123(3):325–330
Baumann M, Suit HD, Sedlacek RS (1990b) Metastases after fractionated radiation therapy of three murine tumor models. Int J Radiat Oncol Biol Phys 19(2):367–370
Baumann M, Petersen C, Krause M (2005) TCP and NTCP in preclinical and clinical research in Europe. Rays 30(2):121–126
Baumann M et al. (2007) EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms. Radiother Oncol 83(3):238–248
Baumann M, Krause M, Hill R (2008) Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 8(7):545–554
Baumann M et al. Cancer stem cells and radiotherapy. Int J Radiat Biol (in press)
Beck-Bornholdt HP (ed) (1993) Current topics in clinical radiobiology of tumors. 1st edn. Springer, Berlin, Heidelberg New York
Begg AC et al. (1999) The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis. Radiother Oncol 50(1):13–23
Bentzen SM (2002) Dose–response relationships in radiotherapy. In: Steel GG (ed) Basic clinical radiobiology. Arnold, London, pp 94–104
Bentzen SM (2005) Theragnostic imaging for radiation oncology: dose-painting by numbers. Lancet Oncol 6(2):112–117
Bentzen SM, Thames HD (1996) Tumor volume and local control probability: clinical data and radiobiological interpretations. Int J Radiat Oncol Biol Phys 36(1):247–251
Bentzen SM, Tucker SL (1997) Quantifying the position and steepness of radiation dose–response curves. Int J Radiat Biol 71(5):531–542
Bentzen SM et al. (2005) Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial. J Clin Oncol 23(24):5560–5567
Bentzen SM et al. (2008a) The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 9(4):331–341
Bentzen SM et al. (2008b) The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 371(9618):1098–1107
Bergonie J, Tribondeau L (1959) Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment. Translation of original article in CR Acad Sci 143:983, 1906. Radiat Res 11:587–588
Bourhis J et al. (2004) Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC). Semin Oncol 31(6):822–826
Bourhis J et al. (2006) Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 368(9538):843–854
Brahme A (1984) Dosimetric precision requirements in radiation therapy. Acta Radiol Oncol 23(5):379–391
Brenner DJ, Hall EJ (1999) Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 43(5):1095–1101
Bristow RG et al. (2007) Homologous recombination and prostate cancer: a model for novel DNA repair targets and therapies. Radiother Oncol 83(3):220–230
Brock WA et al. (1990) Cellular radiosensitivity of primary head and neck squamous cell carcinomas and local tumor control. Int J Radiat Oncol Biol Phys 18(6):1283–1286
Brown JM, Attardi LD (2005) The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 5(3):231–237
Brown JM, Wilson G (2003) Apoptosis genes and resistance to cancer therapy: What does the experimental and clinical data tell us? Cancer Biol Ther 2(5):477–490
Brown JM, Wouters BG (1999) Apoptosis, p53, and tumor cell sensitivity to anticancer agents. Cancer Res 59(7):1391–1399
Buffa FM et al. (2004) Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy. Clin Cancer Res 10(11):3745–3754
Camphausen K et al. (2001) Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res 61(5):2207–2211
Clarke MF et al. (2006) Cancer stem cells: perspectives on current status and future directions: AACR Workshop on Cancer Stem Cells. Cancer Res 66(19):9339–9344
Dincbas FO et al. (2005) The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery. Int J Radiat Oncol Biol Phys 62(3):820–828
Dikomey E et al. (2003) Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts. Toxicology 193(1–2):125–135
Dubben HH, Thames HD, Beck-Bornholdt HP (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47(2):167–174
Eriksen JG et al. (2004a) Molecular profiles as predictive marker for the effect of overall treatment time of radiotherapy in supraglottic larynx squamous cell carcinomas. Radiother Oncol 72(3):275–282
Eriksen JG et al. (2004b) The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys 58(2):561–566
Eriksen JG et al. (2005a) The possible role of TP53 mutation status in the treatment of squamous cell carcinomas of the head and neck (HNSCC) with radiotherapy with different overall treatment times. Radiother Oncol 76(2):135–142
Eriksen JG, Steiniche T, Overgaard J (2005b) The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study. Radiother Oncol 74(2):93–100
Eschwege F et al. (1997) Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience. Int J Radiat Oncol Biol Phys 39(4):849–853
Fletcher GH (1980) Textbook of radiotherapy, 3rd edn. Lea and Febiger, Philadelphia
Fletcher GH (1988) Regaud lecture perspectives on the history of radiotherapy. Radiother Oncol 12(4):iii–v, 253–271
Frankenberg-Schwager M (1989) Review of repair kinetics for DNA damage induced in eukaryotic cells in vitro by ionizing radiation. Radiother Oncol 14(4):307–320
Gerweck LE, Zaidi ST, Zietman A (1994) Multivariate determinants of radiocurability. I: Prediction of single fraction tumor control doses. Int J Radiat Oncol Biol Phys 29(1):57–66
Gilbertson RJ, Rich JN (2007) Making a tumor’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7(10):733–736
Girinsky T et al. (1994) In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: cell characterization and correlations with local control and overall survival. Int J Radiat Oncol Biol Phys 30(4):789–794
Gunderson LL, Martenson JA (1993) Postoperative adjuvant irradiation with or without chemotherapy for rectal carcinoma. Semin Radiat Oncol 3(1):55–63
Hessel F et al. (2004a) Differentiation status of human squamous cell carcinoma xenografts does not appear to correlate with the repopulation capacity of clonogenic tumor cells during fractionated irradiation. Int J Radiat Biol 80(10):719–727
Hessel F et al. (2004b) Repopulation of moderately well-differentiated and keratinizing GL human squamous cell carcinomas growing in nude mice. Int J Radiat Oncol Biol Phys 58(2):510–518
Hill RP, Milas L (1989) The proportion of stem cells in murine tumors. Int J Radiat Oncol Biol Phys 16(2):513–518
Hockel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93(4):266–276
Horiot JC et al. (1992) Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25(4):231–241
Iliakis G (1991) The role of DNA double strand breaks in ionizing radiation-induced killing of eukaryotic cells. Bioessays 13(12):641–648
Jereczek-Fossa BA, Orecchia R (2007) Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for non-metastatic prostate cancer. Radiother Oncol 84(2):197–215
Johnson CR et al. (1995) The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography. Int J Radiat Oncol Biol Phys 33(2):281–287
Kaanders JH et al. (2002) Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer. Cancer Res 62(23):7066–7074
Kasten-Pisula U, Tastan H, Dikomey E (2005) Huge differences in cellular radiosensitivity due to only very small variations in double-strand break repair capacity. Int J Radiat Biol 81(6):409–419
Klokov D et al. (2006) Phosphorylated histone H2AX in relation to cell survival in tumor cells and xenografts exposed to single and fractionated doses of X-rays. Radiother Oncol 80(2):223–229
Krause M et al. (2005) Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation. Radiother Oncol 76(2):162–167
Krause M et al. (2006) Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy. Radiother Oncol 80(2):112–122
Kummermehr J, Trott KR (1997) Tumor stem cells. In: Potten CS (ed) Stem cells Academic Press, London, pp 363–400
Ling CC et al. (2000) Towards multidimensional radiotherapy (MD–CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys 47(3):551–560
Malaise EP et al. (1986) Distribution of radiation sensitivities for human tumor cells of specific histological types: comparison of in vitro to in vivo data. Int J Radiat Oncol Biol Phys 12(4):617–624
Munro TR, Gilbert CW (1961) The relation between tumor lethal doses and the radiosensitivity of tumor cells. Br J Radiol 34:246–251
Nordsmark M et al. (2005) Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 77(1):18–24
Nordsmark M et al. (2007) Differential risk assessments from five hypoxia specific assays: the basis for biologically adapted individualized radiotherapy in advanced head and neck cancer patients. Radiother Oncol 83(3):389–397
Okada H, Mak TW (2004) Pathways of apoptotic and non-apoptotic death in tumor cells. Nat Rev Cancer 4(8):592–603
O’Reilly MS et al. (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79(2):315–328
Overgaard J et al. (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol 6(10):757–764
Petersen C et al. (1998) Linear-quadratic analysis of tumor response to fractionated radiotherapy: a study on human squamous cell carcinoma xenografts. Int J Radiat Biol 73(2):197–205
Petersen C et al. (2001) Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlates with reoxygenation. Int J Radiat Oncol Biol Phys 51(2):483–493
Petersen C et al. (2003) Proliferation and micromilieu during fractionated irradiation of human FaDu squamous cell carcinoma in nude mice. Int J Radiat Biol 79(7):469–477
Quennet V et al. (2006) Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice. Radiother Oncol 81(2):130–135
Ramsay J, Suit HD, Sedlacek R (1988) Experimental studies on the incidence of metastases after failure of radiation treatment and the effect of salvage surgery. Int J Radiat Oncol Biol Phys 14(6):1165–1168
Ramsay J, Ward R, Bleehen NM (1992) Radiosensitivity testing of human malignant gliomas. Int J Radiat Oncol Biol Phys 24(4):675–680
Schmidt-Ullrich RK et al. (1997) Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 15(10):1191–1197
Seigneuric R et al. (2007) Impact of supervised gene signatures of early hypoxia on patient survival. Radiother Oncol 83(3):374–382
Sheldon PW et al. (1974) The incidence of lung metastases in C3H mice after treatment of implanted solid tumors with X-rays or surgery. Br J Cancer 30(4):342–348
SRC Trial Group (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 336(14):980–987
Stausbol-Gron B, Overgaard J (1999) Relationship between tumor cell in vitro radiosensitivity and clinical outcome after curative radiotherapy for squamous cell carcinoma of the head and neck. Radiother Oncol 50(1):47–55
Stuschke M, Thames HD (1999) Fractionation sensitivities and dose-control relations of head and neck carcinomas: analysis of the randomized hyperfractionation trials. Radiother Oncol 51(2):113–121
Stuschke M, Budach V, Sack H (1993) Radioresponsiveness of human glioma, sarcoma, and breast cancer spheroids depends on tumor differentiation. Int J Radiat Oncol Biol Phys 27(3):627–636
Suit HD (1992) Local control and patient survival. Int J Radiat Oncol Biol Phys 23(3):653–660
Suit HD, Westgate SJ (1986) Impact of improved local control on survival. Int J Radiat Oncol Biol Phys 12(4):453–458
Suit H, Shalek R, Wette R (1965) Radiation response of C3H mouse mammary carcinoma evaluated in terms of cellular radiation sensitivity. In: Cellular radiation biology. Williams and Wilkins, Baltimore, pp 514–530
Suit HD, Sedlacek RS, Gillette EL (1970) Examination for a correlation between probabilities of development of distant metastasis and of local recurrence. Radiology 95(1):189–194
Suit HD, Sedlacek R, Thames HD (1987) Radiation dose–response assays of tumor control, in rodent tumor models in experimental cancer therapy. In: Kallman RF (ed) Pergamon Press, New York, pp 138–148
Suit H et al. (1994) Is tumor cell radiation resistance correlated with metastatic ability? Cancer Res 54(7):1736–1741
Taghian A et al. (1993) Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 25(2):243–249
Thames HD, Suit HD (1986) Tumor radioresponsiveness versus fractionation sensitivity. Int J Radiat Oncol Biol Phys 12(4):687–691
Thomas M et al. (1999) Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer. J Clin Oncol 17(4):1185
Thorwarth D, Alber M (2008) Individualised radiotherapy on the basis of functional imaging with FMISO PET. Z Med Phys 18(1):43–50
Todoroki T, Suit HD (1985) Therapeutic advantage in preoperative single-dose radiation combined with conservative and radical surgery in different-size murine fibrosarcomas. J Surg Oncol 29(4):207–215
Van der Kogel AJ (2002) Radiation response and tolerance of normal tissues. In: Steel GG (ed) Basic clinical radiobiology. Arnold, London, pp 30–41
Van’t Veer LJ et al. (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
Vaupel P (2004) Tumor microenvironmental physiology and its implications for radiation oncology. Semin Radiat Oncol 14(3):198–206
Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49(23):6449–6465
Vecchio FM et al. (2005) The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62(3):752–760
Walenta S et al. (2000) High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 60(4):916–921
West CM et al. (1997) The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix. Br J Cancer 76(9):1184–1190
Whelan TJ et al. (2000) Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol 18(6):1220–1229
Williams MV, Denekamp J, Fowler JF (1985) A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation. Int J Radiat Oncol Biol Phys 11(1):87–96
Williams SG et al. (2007) Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer. Int J Radiat Oncol Biol Phys 68(1):24–33
Wouters BG et al. (1999) A p53 and apoptotic independent role for p21waf1 in tumor response to radiation therapy. Oncogene 18(47):6540–6545
Yaromina A et al. (2006) Pimonidazole labelling and response to fractionated irradiation of five human squamous cell carcinoma (hSCC) lines in nude mice: the need for a multivariate approach in biomarker studies. Radiother Oncol 81(2):122–129
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Baumann, M., Krause, M. (2009). Tumor Biology’s Impact on Clinical Cure Rates. In: Molls, M., Vaupel, P., Nieder, C., Anscher, M. (eds) The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74386-6_19
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