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Radiotherapy-Induced Carcinogenesis and Leukemogenesis: Mechanisms and Quantitative Modeling

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ALERT - Adverse Late Effects of Cancer Treatment

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

Biologically-based modeling of spontaneous and radiation-induced carcinogenesis has a history spanning several decades. Such models are important conceptual and quantitative tools, particularly useful whenever cancer risks must be estimated under exposure situations for which no data yet exist, e.g., for novel and prospective radiotherapy protocols. Direct extrapolation from existing data is often not possible due to complex differences between the data sets, but quantitative models can accommodate such extrapolation. Many carcinogenesis models can be characterized as short-term, in that they focus on those processes occurring during and shortly after irradiation. The main advantage of this class of models is that they provide a detailed initial dose response for short-term endpoints which are used as surrogates for carcinogenesis. The main disadvantage is that the possibly substantial modulations of the magnitude and shape of this initial dose response during the lengthy period between irradiation and manifestation of typical solid tumors are not considered. In contrast with the short-term models, another class of biologically-motivated models can be characterized as long-term, in the sense that they track carcinogenesis mechanisms throughout the entire human life span. The main advantages of long-term models are: (1) modulation of the radiation dose response during the long latency period between exposure and diagnosis of cancer is included; and (2) extensive data on spontaneous cancers can be used to help determine the adjustable parameters needed to estimate cancer risks. The main disadvantage is that the early radiation response is typically treated in a less-mechanistic manner than in the short-term models. Here we review some short- and long-term model examples and the carcinogenesis mechanisms which they incorporate. We also discuss an example of unification of both model classes, focusing on application of such formalisms for quantifying radiotherapy-induced second cancer risks.

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References

  • Almog N, Henke V, Flores L et al (2006) Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. Faseb J 20:947–949

    Article  PubMed  CAS  Google Scholar 

  • Anonymous (2004) Cancer survivors: living longer, and now, better. Lancet 364:2153–2154

    Google Scholar 

  • Armitage P (1985) Multistage models of carcinogenesis. Environ Health Perspect 63:195–201

    Article  PubMed  CAS  Google Scholar 

  • Armitage P, Doll R (1954) The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer VIII:1–12

    Google Scholar 

  • BEIR VII Report, Phase 2 (2005) Health risks from exposure to low levels of ionizing radiation. The National Academic Press, Washington

    Google Scholar 

  • Bennett WR, Crew TE, Slack JM et al (2003) Structural-proliferative units and organ growth: effects of insulin-like growth factor 2 on the growth of colon and skin. Development 130:1079–1088

    Article  PubMed  CAS  Google Scholar 

  • Bennett J, Little MP, Richardson S (2004) Flexible dose-response models for Japanese atomic bomb survivor data: Bayesian estimation and prediction of cancer risk. Radiat Environ Biophys 43:233–245

    Article  PubMed  Google Scholar 

  • Bockmuhl U, Petersen I (2002) DNA ploidy and chromosomal alterations in head and neck squamous cell carcinoma. Virchows Arch 441:541–550

    Article  PubMed  Google Scholar 

  • Boice JD Jr, Blettner M, Kleinerman RA et al (1987) Radiation dose and leukemia risk in patients treated for cancer of the cervix. J Natl Cancer Inst 79:1295–1311

    PubMed  Google Scholar 

  • Boice JD Jr, Engholm G, Kleinerman RA et al (1988) Radiation dose and second cancer risk in patients treated for cancer of the cervix. Radiat Res 116:3–55

    Article  PubMed  Google Scholar 

  • Borthwick DW, Shahbazian M, Krantz QT et al (2001) Evidence for stem-cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol 24:662–670

    Article  PubMed  CAS  Google Scholar 

  • Brash DE (2006) Roles of the transcription factor p53 in keratinocyte carcinomas. Br J Dermatol 154(Suppl 1):8–10

    Article  PubMed  CAS  Google Scholar 

  • Brash DE, Zhang W, Grossman D et al (2005) Colonization of adjacent stem cell compartments by mutant keratinocytes. Semin Cancer Biol 15:97–102

    Article  PubMed  CAS  Google Scholar 

  • Brem SS, Gullino PM, Medina D (1977) Angiogenesis: a marker for neoplastic transformation of mammary papillary hyperplasia. Science 195:880–882

    Article  PubMed  CAS  Google Scholar 

  • Brenner DJ, Hahnfeldt P, Amundson SA et al (1996) Interpretation of inverse dose-rate effects for mutagenesis by sparsely ionizing radiation. Int J Radiat Biol 70:447–458

    Article  PubMed  CAS  Google Scholar 

  • Brenner DJ, Curtis RE, Hall EJ et al (2000) Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 88:398–406

    Article  PubMed  CAS  Google Scholar 

  • Brenner DJ, Shuryak I, Russo S et al (2007) Reducing second breast cancers: a potential role for prophylactic mammary irradiation. J Clin Oncol 25:4868–4872

    Article  PubMed  Google Scholar 

  • Brunet A, Rando TA (2007) Ageing: from stem to stern. Nature 449:288–291

    Article  PubMed  CAS  Google Scholar 

  • Calabrese P, Tavare S, Shibata D (2004) Pretumor progression: clonal evolution of human stem cell populations. Am J Pathol 164:1337–1346

    Article  PubMed  Google Scholar 

  • Carlson ME, Conboy IM (2007) Loss of stem cell regenerative capacity within aged niches. Aging Cell 6:371–382

    Article  PubMed  CAS  Google Scholar 

  • Chaturvedi AK, Engels EA, Gilbert ES et al (2007) Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk. J Natl Cancer Inst 99:1634–1643

    Article  PubMed  Google Scholar 

  • Cook PJ, Doll R, Fellingham SA (1969) A mathematical model for the age distribution of cancer in man. Int J Cancer 4:93–112

    Article  PubMed  CAS  Google Scholar 

  • Croizat H, Frindel E, Tubiana M (1980) The effect of partial body irradiation on haemopoietic stem cell migration. Cell Tissue Kinet 13:319–325

    PubMed  CAS  Google Scholar 

  • Curtis SB (1986) Lethal and potentially lethal lesions induced by radiation—a unified repair model. Radiat Res 106:252–270

    Article  PubMed  CAS  Google Scholar 

  • Curtis RE, Boice JD Jr, Stovall M et al (1994) Relationship of leukemia risk to radiation dose following cancer of the uterine corpus. J Natl Cancer Inst 86:1315–1324

    Article  PubMed  CAS  Google Scholar 

  • Curtis SB, Luebeck EG, Hazelton WD et al (2001) The role of promotion in carcinogenesis from protracted high-LET exposure. Phys Med 17(Suppl 1):157–160

    PubMed  Google Scholar 

  • Curtis R, Freedman D, Ron E et al (2006) New malignancies among cancer survivors: SEER Cancer Registries, 1973–2000. National Cancer Institute, Bethesda

    Google Scholar 

  • Dale RG (1986) The application of the linear-quadratic model to fractionated radiotherapy when there is incomplete normal tissue recovery between fractions, and possible implications for treatments involving multiple fractions per day. Br J Radiol 59:919–927

    Article  PubMed  CAS  Google Scholar 

  • Dasu A, Toma-Dasu I, Olofsson J et al (2005) The use of risk estimation models for the induction of secondary cancers following radiotherapy. Acta Oncol 44:339–347

    Article  PubMed  Google Scholar 

  • Feitelson MA, Pan J, Lian Z (2004) Early molecular and genetic determinants of primary liver malignancy. Surg Clin North Am 84:339–354

    Article  PubMed  Google Scholar 

  • Finley JC, Reid BJ, Odze RD et al (2006) Chromosomal instability in Barrett’s esophagus is related to telomere shortening. Cancer Epidemiol Biomarkers Prev 15:1451–1457

    Article  PubMed  CAS  Google Scholar 

  • Fliedner TM (1998) The role of blood stem cells in hematopoietic cell renewal. Stem Cells 16(Suppl 1):13–29

    PubMed  Google Scholar 

  • Fliedner TM, Graessle D, Paulsen C et al (2002) Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm 17:405–426

    Article  PubMed  CAS  Google Scholar 

  • Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778

    Article  PubMed  CAS  Google Scholar 

  • Ghazizadeh S, Taichman LB (2005) Organization of stem cells and their progeny in human epidermis. J Invest Dermatol 124:367–372

    Article  PubMed  CAS  Google Scholar 

  • Gray LH (1957) Radiobiology and cancer. Nature 179:991–994

    Article  PubMed  CAS  Google Scholar 

  • Hahnfeldt P, Hlatky L (1996) Resensitization due to redistribution of cells in the phases of the cell cycle during arbitrary radiation protocols. Radiat Res 145:134–143

    Article  PubMed  CAS  Google Scholar 

  • Hahnfeldt P, Hlatky L (1998) Cell resensitization during protracted dosing of heterogeneous cell populations. Radiat Res 150:681–687

    Article  PubMed  CAS  Google Scholar 

  • Hall EJ, Wuu CS (2003) Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56:83–88

    Article  PubMed  Google Scholar 

  • Hanks GE (1964) In vivo migration of colony-forming units from shielded bone marrow in the irradiated mouse. Nature 203:1393–1395

    Article  PubMed  CAS  Google Scholar 

  • Harding C, Pompei F, Lee EE et al (2008) Cancer suppression at old age. Cancer Res 68:4465–4478

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich WF, Hoogenveen R (2001) Limits of applicability for the deterministic approximation of the two-step clonal expansion model. Risk Anal 21:103–105

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich WF, Paretzke HG (2001) The two-stage clonal expansion model as an example of a biologically based model of radiation-induced cancer. Radiat Res 156:678–681

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich WF, Jacob P, Paretzke HG et al (1999) Two-step model for the risk of fatal and incidental lung tumors in rats exposed to radon. Radiat Res 151:209–217

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich WF, Luebeck EG, Hazelton WD et al (2002) Multistage models and the incidence of cancer in the cohort of atomic bomb survivors. Radiat Res 158:607–614

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich WF, Cullings HM, Funamoto S et al (2007) Promoting action of radiation in the atomic bomb survivor carcinogenesis data? Radiat Res 168:750–756

    Article  PubMed  CAS  Google Scholar 

  • Hlatky L, Hahnfeldt P, Tsionou C et al (1996) Vascular endothelial growth factor: environmental controls and effects in angiogenesis. Br J Cancer Suppl 27:S151–S156

    PubMed  CAS  Google Scholar 

  • Hodgson DC, Koh ES, Tran TH et al (2007) Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer 110:2576–2586

    Article  PubMed  Google Scholar 

  • Hofmann W, Crawford-Brown DJ, Fakir H et al (2006) Modeling lung cancer incidence in rats following exposure to radon progeny. Radiat Prot Dosimetry 122:345–348

    Article  PubMed  CAS  Google Scholar 

  • Inskip PD, Kleinerman RA, Stovall M et al (1993) Leukemia, lymphoma, and multiple myeloma after pelvic radiotherapy for benign disease. Radiat Res 135:108–124

    Article  PubMed  CAS  Google Scholar 

  • Ivanov VK, Gorski AI, Tsyb AF et al (2004) Solid cancer incidence among the Chernobyl emergency workers residing in Russia: estimation of radiation risks. Radiat Environ Biophys 43:35–42

    Article  PubMed  CAS  Google Scholar 

  • Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823

    Article  PubMed  Google Scholar 

  • Koh ES, Tran TH, Heydarian M et al (2007) A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol 2:13

    Article  PubMed  Google Scholar 

  • Kohle C, Schwarz M, Bock KW (2008) Promotion of hepatocarcinogenesis in humans and animal models. Arch Toxicol 82:623–631

    Article  PubMed  CAS  Google Scholar 

  • Komarova NL, Cheng P (2006) Epithelial tissue architecture protects against cancer. Math Biosci 200:90–117

    Article  PubMed  Google Scholar 

  • Kopp-Schneider A, Portier CJ (1991) Distinguishing between models of carcinogenesis: the role of clonal expansion. Fundam Appl Toxicol 17:601–613

    Article  PubMed  CAS  Google Scholar 

  • Lange CS, Mayer PJ, Reddy NM (1997) Tests of the double-strand break, lethal-potentially lethal and repair-misrepair models for mammalian cell survival using data for survival as a function of delayed-plating interval for log-phase Chinese hamster V79 cells. Radiat Res 148:285–292

    Article  PubMed  CAS  Google Scholar 

  • Leedham SJ, Wright NA (2008) Expansion of a mutated clone—from stem cell to tumour. J Clin Pathol 61(2):164–171

    Google Scholar 

  • Leedham SJ, Schier S, Thliveris AT et al (2005) From gene mutations to tumours–stem cells in gastrointestinal carcinogenesis. Cell Prolif 38:387–405

    Article  PubMed  CAS  Google Scholar 

  • Li L, Xie T (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21:605–631

    Article  PubMed  CAS  Google Scholar 

  • Lindsay KA, Wheldon EG, Deehan C et al (2001) Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy. Br J Radiol 74:529–536

    PubMed  CAS  Google Scholar 

  • Little MP (2001) Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors. Int J Radiat Biol 77:431–464

    Article  PubMed  CAS  Google Scholar 

  • Little MP (2007) A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia. J Theor Biol 245:83–97

    Article  PubMed  CAS  Google Scholar 

  • Little MP, Li G (2007) Stochastic modelling of colon cancer: is there a role for genomic instability? Carcinogenesis 28:479–487

    Article  PubMed  CAS  Google Scholar 

  • Little MP, Wright EG (2003) A stochastic carcinogenesis model incorporating genomic instability fitted to colon cancer data. Math Biosci 183:111–134

    Article  PubMed  CAS  Google Scholar 

  • Little MP, Weiss HA, Boice JD Jr et al (1999) Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis. Radiat Res 152:280–292

    Article  PubMed  CAS  Google Scholar 

  • Luebeck EG, Hazelton WD (2002) Multistage carcinogenesis and radiation. J Radiol Prot 22:A43–A49

    Article  PubMed  CAS  Google Scholar 

  • Luebeck EG, Moolgavkar SH (2002) Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci U S A 99:15095–15100

    Article  PubMed  CAS  Google Scholar 

  • Maley CC (2007) Multistage carcinogenesis in Barrett’s esophagus. Cancer Lett 245:22–32

    Article  PubMed  CAS  Google Scholar 

  • Maley CC, Reid BJ (2005) Natural selection in neoplastic progression of Barrett’s esophagus. Semin Cancer Biol 15:474–483

    Article  PubMed  CAS  Google Scholar 

  • McDonald SA, Preston SL, Greaves LC et al (2006) Clonal expansion in the human gut: mitochondrial DNA mutations show us the way. Cell Cycle 5:808–811

    Article  PubMed  CAS  Google Scholar 

  • Mebust M, Crawford-Brown D, Hofmann W et al (2002) Testing extrapolation of a biologically based exposure-response model from in vitro to in vivo conditions. Regul Toxicol Pharmacol 35:72–79

    Article  PubMed  CAS  Google Scholar 

  • Meza R, Jeon J, Moolgavkar SH et al (2008) Age-specific incidence of cancer: phases, transitions, and biological implications. Proc Natl Acad Sci U S A 105:16284–16289

    Article  PubMed  CAS  Google Scholar 

  • Michor F, Iwasa Y, Komarova NL et al (2003a) Local regulation of homeostasis favors chromosomal instability. Curr Biol 13:581–584

    Article  PubMed  CAS  Google Scholar 

  • Michor F, Frank SA, May RM et al (2003b) Somatic selection for and against cancer. J Theor Biol 225:377–382

    Article  PubMed  CAS  Google Scholar 

  • Michor F, Iwasa Y, Rajagopalan H et al (2004) Linear model of colon cancer initiation. Cell Cycle 3:358–362

    Article  PubMed  CAS  Google Scholar 

  • Michor F, Iwasa Y, Lengauer C et al (2005) Dynamics of colorectal cancer. Semin Cancer Biol 15:484–493

    Article  PubMed  CAS  Google Scholar 

  • Midorikawa Y, Makuuchi M, Tang W et al (2007) Microarray-based analysis for hepatocellular carcinoma: from gene expression profiling to new challenges. World J Gastroenterol 13:1487–1492

    PubMed  CAS  Google Scholar 

  • Moolgavkar SH (1978) The multistage theory of carcinogenesis and the age distribution of cancer in man. J Natl Cancer Inst 61:49–52

    PubMed  CAS  Google Scholar 

  • Moolgavkar S (1980) Multistage models for carcinogenesis. J Natl Cancer Inst 65:215–216

    PubMed  CAS  Google Scholar 

  • Moolgavkar SH (1983) Model for human carcinogenesis: action of environmental agents. Environ Health Perspect 50:285–291

    Article  PubMed  CAS  Google Scholar 

  • Moolgavkar SH (1986) Carcinogenesis modeling: from molecular biology to epidemiology. Annu Rev Public Health 7:151–169

    Article  PubMed  CAS  Google Scholar 

  • Moolgavkar SH, Knudson AG Jr (1981) Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst 66:1037–1052

    PubMed  CAS  Google Scholar 

  • Naumov GN, Bender E, Zurakowski D et al (2006) A model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst 98:316–325

    Article  PubMed  Google Scholar 

  • NCRP Report 136 (2001) Evaluation of the linear-nonthreshold dose-response model for ionizing radiation. The National Academic Press, Washington

    Google Scholar 

  • Neglia JP, Robison LL, Stovall M et al (2006) New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98:1528–1537

    Article  PubMed  Google Scholar 

  • Nguyen LN, Ang KK (2002) Radiotherapy for cancer of the head and neck: altered fractionation regimens. Lancet Oncol 3:693–701

    Article  PubMed  Google Scholar 

  • Nilsson P, Thames HD, Joiner MC (1990) A generalized formulation of the ‘incomplete-repair’ model for cell survival and tissue response to fractionated low dose-rate irradiation. Int J Radiat Biol 57:127–142

    Article  PubMed  CAS  Google Scholar 

  • Nishimura M, Furumoto H, Kato T et al (2000) Microsatellite instability is a late event in the carcinogenesis of uterine cervical cancer. Gynecol Oncol 79:201–206

    Article  PubMed  CAS  Google Scholar 

  • Nordling CO (1953) A new theory on the cancer inducing mechanism. Br J Cancer 7:68–72

    Article  PubMed  CAS  Google Scholar 

  • Nowak MA, Komarova NL, Sengupta A et al (2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A 99:16226–16231

    Article  PubMed  CAS  Google Scholar 

  • Nowak MA, Michor F, Iwasa Y (2006) Genetic instability and clonal expansion. J Theor Biol 241:26–32

    Article  PubMed  CAS  Google Scholar 

  • Ohtaki M, Niwa O (2001) A mathematical model of radiation carcinogenesis with induction of genomic instability and cell death. Radiat Res 156:672–677

    Article  PubMed  CAS  Google Scholar 

  • Ottolenghi A, Ballarini F, Merzagora M (1999) Modelling radiation-induced biological lesions: from initial energy depositions to chromosome aberrations. Radiat Environ Biophys 38:1–13

    Article  PubMed  CAS  Google Scholar 

  • Perez-Ordonez B, Beauchemin M, Jordan RC (2006) Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 59:445–453

    Article  PubMed  CAS  Google Scholar 

  • Pierce DA, Mendelsohn ML (1999) A model for radiation-related cancer suggested by atomic bomb survivor data. Radiat Res 152:642–654

    Article  PubMed  CAS  Google Scholar 

  • Pierce DA, Vaeth M (2003) Age-time patterns of cancer to be anticipated from exposure to general mutagens. Biostatistics 4:231–248

    Article  PubMed  Google Scholar 

  • Pompei F, Wilson R (2002) A quantitative model of cellular senescence influence on cancer and longevity. Toxicol Ind Health 18:365–376

    Article  PubMed  Google Scholar 

  • Pompei F, Polkanov M, Wilson R (2001) Age distribution of cancer in mice: the incidence turnover at old age. Toxicol Ind Health 17:7–16

    Article  PubMed  CAS  Google Scholar 

  • Potten CS, Booth C (2002) Keratinocyte stem cells: a commentary. J Invest Dermatol 119:888–899

    Article  PubMed  CAS  Google Scholar 

  • Radivoyevitch T, Kozubek S, Sachs RK (2001) Biologically based risk estimation for radiation-induced CML. Inferences from BCR and ABL geometric distributions. Radiat Environ Biophys 40:1–9

    Article  PubMed  CAS  Google Scholar 

  • Ritter G, Wilson R, Pompei F et al (2003) The multistage model of cancer development: some implications. Toxicol Ind Health 19:125–145

    Article  PubMed  Google Scholar 

  • Ron E (2006) Childhood cancer—treatment at a cost. J Natl Cancer Inst 98:1510–1511

    Article  PubMed  Google Scholar 

  • Ronckers CM, Sigurdson AJ, Stovall M et al (2006) Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res 166:618–628

    Article  PubMed  CAS  Google Scholar 

  • Rossi HH, Kellerer AM (1986) The dose rate dependence of oncogenic transformation by neutrons may be due to variation of response during the cell cycle. Int J Radiat Biol Relat Stud Phys Chem Med 50:353–361

    Article  PubMed  CAS  Google Scholar 

  • Rusyn I, Peters JM, Cunningham ML (2006) Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit Rev Toxicol 36:459–479

    Article  PubMed  CAS  Google Scholar 

  • Sachs RK, Brenner DJ (2005) Solid tumor risks after high doses of ionizing radiation. Proc Natl Acad Sci U S A 102:13040–13045

    Article  PubMed  CAS  Google Scholar 

  • Sachs RK, Chan M, Hlatky L et al (2005) Modeling intercellular interactions during carcinogenesis. Radiat Res 164:324–331

    Article  PubMed  CAS  Google Scholar 

  • Sachs RK, Shuryak I, Brenner D et al (2007) Second cancers after fractionated radiotherapy: stochastic population dynamics effects. J Theor Biol 249:518–531

    Article  PubMed  Google Scholar 

  • Schneider U, Kaser-Hotz B (2005) Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose-response relationships. Radiat Environ Biophys 44:235–239

    Article  PubMed  Google Scholar 

  • Schneider U, Walsh L (2008) Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy. Radiat Environ Biophys 47:253–263

    Article  PubMed  Google Scholar 

  • Schollnberger H, Mitchel RE, Crawford-Brown DJ et al (2002) Nonlinear dose-response relationships and inducible cellular defence mechanisms. J Radiol Prot 22:A21–A25

    Article  PubMed  Google Scholar 

  • Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8:703–713

    Article  PubMed  CAS  Google Scholar 

  • Shaw IC, Jones HB (1994) Mechanisms of non-genotoxic carcinogenesis. Trends Pharmacol Sci 15:89–93

    Article  PubMed  CAS  Google Scholar 

  • Shuryak I, Sachs RK, Hlatky L et al (2006) Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks. J Natl Cancer Inst 98:1794–1806

    Article  PubMed  Google Scholar 

  • Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner DJ (2009a) A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: approach. Radiat Environ Biophys 48(3):263–274 (Erratum in: Radiat Environ Biophys 50(4):607–608)

    Google Scholar 

  • Shuryak I, Hahnfeldt P, Hlatky L, Sachs RK, Brenner DJ (2009b) A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation. Radiat Environ Biophys 48(3):275–286 (Erratum in: Radiat Environ Biophys 50(4):607–608)

    Google Scholar 

  • Slack JM (2000) Stem cells in epithelial tissues. Science 287:1431–1433

    Article  PubMed  CAS  Google Scholar 

  • Sontag W (1997) A discrete cell survival model including repair after high dose-rate of ionizing radiation. Int J Radiat Biol 71:129–144

    Article  PubMed  CAS  Google Scholar 

  • Spiess PE, Czerniak B (2006) Dual-track pathway of bladder carcinogenesis: practical implications. Arch Pathol Lab Med 130:844–852

    PubMed  CAS  Google Scholar 

  • Stewart RD (2001) Two-lesion kinetic model of double-strand break rejoining and cell killing. Radiat Res 156:365–378

    Article  PubMed  CAS  Google Scholar 

  • Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349

    PubMed  Google Scholar 

  • Tamura G (2006) Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol 12:192–198

    PubMed  CAS  Google Scholar 

  • Thames HD (1985) An ‘incomplete-repair’ model for survival after fractionated and continuous irradiations. Int J Radiat Biol Relat Stud Phys Chem Med 47:319–339

    Article  PubMed  CAS  Google Scholar 

  • Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549

    Article  PubMed  CAS  Google Scholar 

  • Tobias CA (1985) The repair-misrepair model in radiobiology: comparison to other models. Radiat Res Suppl 8:S77–S95

    Article  PubMed  CAS  Google Scholar 

  • Travis LB, Andersson M, Gospodarowicz M et al (2000) Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92:1165–1171

    Article  PubMed  CAS  Google Scholar 

  • Travis LB, Gospodarowicz M, Curtis RE et al (2002) Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease. J Natl Cancer Inst 94:182–192

    Article  PubMed  Google Scholar 

  • Travis LB, Hill DA, Dores GM et al (2003) Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290:465–475

    Article  PubMed  Google Scholar 

  • Trosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 Gene, cell–cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 1089:36–58

    Article  PubMed  CAS  Google Scholar 

  • Upton AC (2003) The state of the art in the 1990’s: NCRP Report No. 136 on the scientific bases for linearity in the dose-response relationship for ionizing radiation. Health Phys 85:15–22

    Article  PubMed  CAS  Google Scholar 

  • Weiss HA, Darby SC, Fearn T et al (1995) Leukemia mortality after X-ray treatment for ankylosing spondylitis. Radiat Res 142:1–11

    Article  PubMed  CAS  Google Scholar 

  • Wheldon EG, Lindsay KA, Wheldon TE (2000) The dose-response relationship for cancer incidence in a two-stage radiation carcinogenesis model incorporating cellular repopulation. Int J Radiat Biol 76:699–710

    Article  PubMed  CAS  Google Scholar 

  • Yakovlev A, Polig E (1996) A diversity of responses displayed by a stochastic model of radiation carcinogenesis allowing for cell death. Math Biosci 132:1–33

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki H, Mesnil M, Nakazawa H (1992) Interaction and distinction of genotoxic and non-genotoxic events in carcinogenesis. Toxicol Lett 64–65 Spec No:597–604

    Google Scholar 

  • Zaider M, Wuu CS (1995) The effects of sublethal damage recovery and cell cycle progression on the survival probability of cells exposed to radioactive sources. Br J Radiol 68:58–63

    Article  PubMed  CAS  Google Scholar 

  • Zelefsky MJ, Fuks Z, Hunt M et al (2002) 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

    Article  PubMed  Google Scholar 

  • Zhang W, Remenyik E, Zelterman D et al (2001) Escaping the stem cell compartment: sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proc Natl Acad Sci U S A 98:13948–13953

    Article  PubMed  CAS  Google Scholar 

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Brenner, D.J., Shuryak, I., Sachs, R.K. (2014). Radiotherapy-Induced Carcinogenesis and Leukemogenesis: Mechanisms and Quantitative Modeling. In: Rubin, P., Constine, L., Marks, L. (eds) ALERT - Adverse Late Effects of Cancer Treatment. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72314-1_14

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