Advertisement
Review| Volume 91, ISSUE 1, P4-15, April 2009

Download started.

Ok

Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review

Published:February 09, 2009DOI:https://doi.org/10.1016/j.radonc.2008.12.016

      Abstract

      Second primary malignancies (SPMs) occurring after oncological treatment have become a major concern during the past decade. Their incidence has long been underestimated because most patients had a short life expectancy after treatment or their follow-up was shorter than 15 years. With major improvement of long-term survival, longer follow-up, cancer registries and end-result programs, it was found that the cumulative incidence of SPM could be as high as 20% of patients treated by radiotherapy. This cumulative proportion varies with several factors, which ought to be studied more accurately. The delay between irradiation and solid tumor emergence is seldom shorter than 10 years and can be as long as half a century. Thus, inclusion in a cohort of patients with a short follow-up leads to an underestimation of the proportion of SPM caused by treatment, unless actuarial cumulative incidence is computed. The incidence varies with the tissue and organs, the age of the patient at treatment, hereditary factors, but also, and probably mainly, with dose distribution, size of the irradiated volume, dose, and dose-rate.
      An effort toward a reduction in their incidence is mandatory. Preliminary data suggest that SPMs are mainly observed in tissues having absorbed doses above 2 Gy (fractionated irradiation) and that their incidence increases with the dose. However, in children thyroid and breast cancers are observed following doses as low as 100 mGy, and in adults lung cancers have been reported for doses of 500 mGy, possibly due to interaction with tobacco. The dose distribution and the dose per fraction have a major impact. However, the preliminary data regarding these factors need confirmation. Dose-rates appear to be another important factor. Some data suggest that certain patients, who could be identified, have a high susceptibility to radiocancer induction.
      Efforts should be made to base SPM reduction on solid data and not on speculation or models built on debatable hypotheses regarding the dose-carcinogenic effect relationship. In parallel, radiation therapy philosophy must evolve, and the aim of treatment should be to deliver the minimal effective radiation therapy rather than the maximal tolerable dose.

      Keyword

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Suit H.
        • Goldberg S.
        • Niemierko A.
        • et al.
        Secondary carcinogenesis in patients treated with Radiation: A review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects.
        Radiat Res. 2007; 167: 12-42
      1. Trott KR. Second cancers after radiotherapy. In: van der Kogel, Joiner, editors. Basic clinical radiobiology. London: Hodder publ.; 2008 (in press).

        • Dörr W.
        • Herrmann T.
        Cancer induction by radiotherapy: dose dependence and spatial relationship to irradiated volume.
        J Radiol Prot. 2002; 22: A117-A121
        • Rubino C.
        • de Vathaire F.
        • Shamsaldin A.
        • et al.
        Radiation dose chemotherapy, hormonal treatment and risk of second cancer after breast cancer treatment.
        Brit J Cancer. 2003; 89: 840-846
        • Little M.P.
        • de Vathaire F.
        • Charles M.W.
        • Hawkins M.M.
        • Muirhead C.R.
        Variations with time and age in the risks of solid cancer incidence after radiation exposure in childhood.
        Stat Med. 1998; 17: 1341-1355
      2. Hall EJ, Giaccia A. radiobiology for the radiologist. Lippincott, Williams and Wilkins; 2006.

      3. Tubiana M, editor. Radiobiologie. Hermann/Médecine: Paris; 2008. 502 pages.

        • Loeffler J.
        • Niermierk A.
        • Chapman P.
        Second tumor after radiosurgery: tip of the iceberg or a bump in the road?.
        Neurosurgery. 2003; 52: 1436-1442
        • Richiardi L.
        • Scelo G.
        • Boffetta P.
        • et al.
        Second malignancies among survivors of germ-cell testicular cancer: a pooled analysis between 13 cancer registries.
        Int J Cancer. 2006; 120: 623-636
        • Scelo G.
        • Boffetta P.
        • Hemminki K.
        • et al.
        Association between small intestine cancer and other primary cancers: an international population-based study.
        Int J Cancer. 2006; 118: 189-196
        • Monier R.
        • Tubiana M.
        Cancérogenèse: accroissement des connaissances et évolution des concepts.
        Oncologie. 2008; 10: 319-347
        • Trott K.R.
        • Roseman M.
        Molecular mechanism of radiation carcinogenesis and the linear non-threshold dose response model of radiation risk estimation.
        Radiat Environ Biophys. 2000; 39: 79-87
        • Ames B.N.
        • Gold L.S.
        Too many rodent carcinogens: mitogenesis increases mutagenesis.
        Science. 1990; 249: 970-971
        • Ames B.N.
        • Gold L.S.
        Environmental pollution, pesticides and the prevention of cancer: misconceptions.
        FASEB J. 1997; 11: 1041-1052
      4. Académie Nationale de Médecine, Institut de France – Académie des Sciences (March 30, 2005) Joint Report no. 2. In: Tubiana M, Aurengo A, Averbeck D, Bonnin A, Le Guen B, Masse R, Monier R, Valleron AJ, de Vathaire F, editors. Dose-effect relationships and the estimation of the carcinogenic effects of low doses of ionizing radiation. (English Translation) (www.academiemedecine.fr/actualites/rapports.asp) (Paris Nucleon 2005) ISBN 2-84332-018-6.

        • Baylin S.B.
        • Ohm J.E.
        Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction.
        Nat Rev/Cancer. 2006; 6: 107-116
        • Cohen S.M.
        • Ellwein L.B.
        Cell proliferation in carcinogenesis.
        Science. 1990; 249: 503-504
        • Derksen P.W.
        • Tjin E.
        • Meijer H.P.
        • et al.
        Illegitimate Wnt signaling promotes proliferation of multiple myeloma cells.
        Proc Natl Acad Sci USA. 2004; 101: 6122-6127
        • Brash D.E.
        Sunlight and the onset of skin cancer.
        Trends Genet. 1997; 13: 410-414
        • Gould M.N.
        Radiation initiation of carcinogenesis in vivo: a rare or common cellular event.
        in: Boice Jr., J.D. Fraumeni Jr., J.F. Radiation carcinogenesis: epidemiology and biological significance. Raven Press, New York1984: 347-358
        • Kennedy A.R.
        • Little J.
        Evidence that a second event in X-ray induced oncogenic transformation in vitro occurs during cellular proliferation.
        Radiat Res. 1984; 99: 228-248
        • Bartkova J.
        • Rezaci N.
        • Liontos M.
        • et al.
        Oncogene induced senescence is part of the tumorigenesis barrier imposed by the DNA damage checkpoints.
        Nature. 2006; 444: 633-637
        • Campisi J.
        Senescent cells, tumor suppression and organism aging.
        Cell. 2005; 120: 513-522
        • Schmitt C.A.
        Cellular senescence and cancer treatment.
        Biochim Biophys Acta. 2007; 1775: 5-20
        • Hoeijmakers J.H.J.
        Genome maintenance mechanisms for preventing cancer.
        Nature. 2001; 411: 366-374
        • Sancar A.
        • Lindsey-Boltz L.A.
        • Unsal-Kacmaz K.
        • Linn S.
        Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.
        Annu Rev Biochem. 2004; 73: 39-85
        • Averbeck D.
        • Testard L.
        • Boucher D.
        Changing views on ionizing radiation-induced cellular effects.
        Int J Low Radiat. 2006; 3: 117-134
        • Boucher D.
        • Hindo J.
        • Averbeck D.
        Increased repair of gamma-induced DNA double-strand breaks at lower dose-rate in CHO cells.
        Can J Physiol Pharmacol. 2004; 82: 125-132
        • Barnes D.E.
        • Lindahl T.
        Repair and genetic consequences of endogenous DNA base damage in mammalian cells.
        Annu Rev Genet. 2004; 38: 445-476
        • Hickman J.A.
        Apoptosis and tumorigenesis.
        Cur Opin Cell Biol. 2002; 12: 67-72
        • Lyng F.M.
        • Maguire P.
        • Kilmurray N.
        • Mothersill C.
        • et al.
        Apoptosis is initiated in human keratinocytes exposed to signaling factors from microbeam irradiated cells.
        Int J Radiat Biol. 2006; 82: 393-399
        • Portess D.I.
        • Bauer G.
        • Hill M.A.
        • et al.
        Low-dose irradiation on nontransformed cells stimulates the selective removal of precancerous cells via intercellular induction of apoptosis.
        Cancer Res. 2007; 67: 1246-1253
        • Rothkamm K.
        • Löbrich M.
        Evidence for a lack of DNA double-strand break repair in human cells exposed to very low X-ray doses.
        Proc Natl Acad Sci USA. 2003; 100: 5057-5062
        • Collis S.J.
        • Schwaninger J.M.
        • Ntambi A.J.
        • et al.
        Evasion of early cellular response mechanisms following low level radiation induced DNA damage.
        J Biol Chem. 2004; 279: 49624-49632
        • Bauer G.
        Low dose radiation and intercellular induction of apoptosis: potential implication for the control of oncogenesis.
        Int J Radiat Biol. 2007; 83: 1-16
        • Hahn W.C.
        • Weinberg R.A.
        Rules for making human tumor cells.
        New Engl J Med. 2002; 347: 1593-1603
      5. Weinberg RA. The biology of cancer. New York: Taylor & Francis; 2007.

        • Barcellos-Hoff M.H.
        • Ravani S.A.
        Irradiated gland mammary stroma promotes tumorogenic potential by unirradiated epithelial cells.
        Cancer Res. 2000; 60: 1254-1260
        • Barcellos-Hoff M.H.
        Integrative radiation carcinogenesis: interactions between cell and tissue responses to DNA damage.
        Sem Cancer Biol. 2005; 15: 138-148
        • Radisky D.C.
        • Bissell M.J.
        Cancer. Respect thy neighbor!.
        Science. 2004; 303: 774-775
        • Carnes B.A.
        • Groer P.G.
        • Kotec T.J.
        Radium dial workers: issues concerning dose response and modeling.
        Radiat Res. 1997; 147: 707-714
        • Nyberg U.
        • Nilsson B.
        • Travis L.B.
        • et al.
        Cancer incidence among Swedish patients exposed to radioactive thorotrast: a forty-year follow-up survey.
        Radiat Res. 2002; 157: 419-425
        • Van Kaick G.
        • Dalheimer A.
        • Hornik S.
        • et al.
        The German thorostrast study: recent results and assessment of risks.
        Radiat Res. 1999; 152: S64-S72
        • Wolff S.
        The adaptive response in radiobiology: evolving insights and implications.
        Environ Health Perspect. 1998; 106: 277-283
        • Day T.K.
        • Zeng G.
        • Hooker A.M.
        • et al.
        Adaptive response for chromosomal inversions on pKZ1 mouse prostate induced by low doses of X radiation delivered after a high dose.
        Radiat Res. 2007; 167: 682-692
        • Brenner D.J.
        • Doll R.
        • Goodhead D.T.
        • et al.
        Cancer risk attributable to low doses of ionizing radiation: assessing what we really know.
        Proc Natl Acad Sci USA. 2003; 100: 13761-13766
      6. BEIR VII Phase 2: Health risks from exposure to low levels of ionizing radiation. Board on radiation effects research 2006. National Academies press. Available from: <http://netonnapedu/books/030909156X/html/>.

        • Brenner D.J.
        • Sachs R.K.
        Estimating radiation-induced cancer risks at very low doses: rationale for using a linear no-threshold approach.
        Radiat Environ Biophys. 2006; 44: 253-256
      7. ICRP, Low-dose extrapolation of radiation-related cancer risk. Publication 99. International Commission on Radiological Protection. Elsevier, Amsterdam; 2006.

        • Tubiana M.
        • Aurengo A.
        • Averbeck D.
        • Masse R.
        The debate on the use of linear on threshold for assessing the effects of low doses.
        J Radiol Prot. 2006; 26: 317-324
        • Tubiana M.
        The linear no-threshold relationship and advances in our understanding of carcinogenesis.
        Int J Low Rad. 2008; 5: 173-204
      8. Tubiana M, Feinendegen L, Chichuan Y, Kaminski JM. The linear no-threshold relationship is inconsistent with radiobiological and experimental data. Radiology, in press.

        • Charles M.W.
        LNT – an apparent rather than a real controversy?.
        J Radiol Prot. 2006; 26: 325-329
        • Wall B.F.
        • Kendall G.M.
        • Edwards A.A.
        • Bouffler S.
        • Muirhead C.R.
        • Meara J.R.
        What are the risks from medical X-rays and other low dose radiation?.
        Br J Radiol. 2006; 79: 285-294
        • Belyakov O.V.
        • Folkard M.
        • Mothersill C.
        Bystander induced differentiation. A major response to targeted irradiation of a urothelial explant model.
        Mutat Res. 2006; 597: 43-49
        • Liu Z.
        • Mothersill C.E.
        • McNeill F.E.
        • et al.
        A dose threshold for a medium transfer bystander effect for a human skin cell line.
        Radiat Res. 2006; 166: 19-23
        • Morgan W.F.
        Will radiation-induced bystander effects or adaptive responses impact on the shape of the dose response relationships at low doses of ionizing radiation.
        Dose Response. 2006; 4: 257-262
        • Mothersill C.
        • Seymour C.B.
        Radiation-induced bystander effects and the DNA paradigm: an “out of field” perspective.
        Mutat Res. 2006; 59: 5-10
        • Smith R.W.
        • Wang J.
        • Bucking C.P.
        • Mothersill C.E.
        • Seymour C.B.
        Evidence for a protective response by the gill proteome of rainbow trout exposed to X-ray induced bystander signals.
        Proteomics. 2007; 7: 4171-4180
        • Leonard B.E.
        Adaptive response and human benefit: part I – a microdosimetric dose dependent model.
        Int J Radiat Biol. 2007; 83: 115-131
        • Leonard B.E.
        Adaptive response: Part II – Modeling for dose rate and time influences.
        Int J Radiat Biol. 2007; 83: 395-408
        • Streffer C.
        Bystander effects, adaptive response and genomic instability induced by prenatal irradiation.
        Rev Mutat Res. 2004; 568: 79-87
        • Okada M.
        • Okabe A.
        • Uchihori Y.
        • et al.
        Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells.
        Br J Cancer. 2007; 96: 1707-1710
        • Kadhim M.A.
        • Hill M.A.
        • Moore S.R.
        Genomic instability and the role of radiation quality.
        Radiat Prot Dos. 2006; 122: 221-227
        • Chalmers A.
        • Johnston P.
        • Woodcock M.
        • Joiner M.
        • Marples B.
        PARP-1, PARP-2, and the cellular response to low doses of ionizing radiation.
        Int J Radiat Oncol Biol Phys. 2004; 58: 410-419
        • Marples B.
        • Wouters B.G.
        • Collis S.J.
        • Chalmers A.J.
        • Joiner M.C.
        Low-dose hyper-radiosensitivity: a consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells.
        Radiat Res. 2004; 161: 247-255
        • Boulton E.
        • Cleary H.
        • Papworth D.
        • Plumb M.
        Susceptibility to radiation-induced leukaemia-lymphoma is genetically separable from sensitivity to radiation-induced genomic instability.
        Int J Radiat Biol. 2001; 77: 21-29
        • Hayata J.
        • Wang C.
        • Zhang W.
        • et al.
        Effect of high level natural radiation on chromosomes of residents in southern china.
        Cytogenet Genome Res. 2004; 104: 237-239
        • Preston D.L.
        • Pierce D.A.
        • Shimizu Y.
        • Cullings H.M.
        • Fujita S.
        • Funamoto S.
        • Kodama K.
        Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates.
        Radiat Res. 2004; 162: 377-389
        • Preston D.L.
        • Ron E.
        • Tokuoka S.
        • et al.
        Solid cancer incidence in atomic bomb survivors: 1958–1998.
        Radiat Res. 2007; 168: 1-64
        • Chaturvedi A.K.
        • Engels E.A.
        • Gilbert E.S.
        • et al.
        Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk.
        J Natl Cancer Inst. 2007; 99: 1634-1643
        • Kirova Y.
        • Vilcoq J.
        • Asselain B.
        • et al.
        Radiation-induced sarcomas after radiotherapy for breast carcinoma.
        Cancer. 2005; 104: 856-863
        • Taghian A.
        • de Vathaire F.
        • Terreir P.
        • et al.
        Long-term risk of sarcoma following radiation treatment for breast cancer.
        Int J Radiat Oncol Biol Phys. 1991; 21: 361-367
        • Cardis E.
        • Kesminienne A.
        • Ivanov V.
        • et al.
        Risk of thyroid cancer after exposure to I131 in childhood.
        J Nat Cancer Inst. 2005; 97: 724-732
        • Cardis E.
        • Howe G.
        • Ron E.
        • et al.
        Cancer consequences of the chernobyl accident: 20 years after.
        J Radiol Prot. 2006; 26: 127-140
      9. de Vathaire F. Annexe 4: Les données épidémiologiques. In: Rapport conjoint no. 2 Académie Nationale de Médecine, Institut de France – Académie des Sciences (30 mars 2005) (M. Tubiana, A. Aurengo, D. Averbeck, et al.) La relation dose-effet et l’estimation des effets cancérogènes des faibles doses de rayonnements ionisants (Edition Nucleon); 2005, p. 147–68.

        • de Vathaire F.
        • Hardiman C.
        • Shamsaldin A.
        • et al.
        Thyroid carcinoma following irradiation for a first cancer during childhood.
        Arch Int Med. 2000; 159: 2713-2719
      10. ICRP Publication 60 – Ann. ICRP 21, Nos 1–3. Pergamon Press; 1991.

      11. ICRP Publication 103 – Ann. ICRP 37, Nos 2–4. Elsevier; 2007.

        • Verkooijen R.B.T.
        • Smit J.W.A.
        • Romijn J.A.
        • Stokkel M.P.
        The incidence of second primary tumors in thyroid cancer patients is increased but not related to treatment of thyroid cancer.
        Eur J Endocrinol. 2006; 155: 801-806
        • Akolen L.A.
        • Glattre E.
        Second malignancies in thyroid cancer patients: a population-based survey of 3658 cases from Norway.
        Eur J Cancer. 1992; 28: 491-495
        • Berthe E.
        • Henry-Amar M.
        • Michielo J.J.
        • et al.
        Risk of second primary cancer following differentiated thyroid cancer.
        Eur J Nucl Med. 2004; 31: 685-691
        • Chen A.Y.
        • Levy L.
        • Goepfert H.
        • et al.
        The development of breast carcinoma in women with thyroid carcinoma.
        Cancer. 2001; 92: 225-231
        • Kony S.J.
        • de Vathaire F.
        • Chompat A.
        • et al.
        Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood.
        Lancet. 1997; 350: 91-96
        • Boice J.D.
        • Engholm G.
        • Kleinerman R.A.
        • et al.
        Radiation dose and second cancer risk in patients treated for cancer of the cervix.
        Radiat Res. 1988; 116: 3-55
        • Kleinerman R.
        • Boice J.
        • Storm H.
        • Sparen P.
        • Andersen A.
        • Pukukala E.
        • et al.
        Second primary cancer after treatment for cervical cancer. An international cancer registries study.
        Cancer. 1995; 76: 442-452
        • Weiss H.
        • Darby S.
        • Doll R.
        Cancer mortality following X-ray treatment for ankylosing spondylitis.
        Int J Cancer. 1994; 59: 327-338
        • Clarke M.
        • Collins R.
        • Darby S.
        • et al.
        Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.
        Lancet. 2005; 366: 2087-2106
        • Roychoudhuri R.
        • Evans H.
        • Robinson D.
        • Moller H.
        Radiation-induced malignancies following radiotherapy for breast cancer.
        Brit J Cancer. 2004; 91: 568-572
        • Darby S.C.
        • McGale P.
        • Taylor C.W.
        • Peto R.
        Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries.
        Lancet Oncol. 2005; 6: 557-565
        • Brown L.M.
        • Chen B.E.
        • Pfeiffer R.M.
        • et al.
        Risk of second non-hematological malignancies among 376,825 breast cancer survivors.
        Breast Cancer Res Treat. 2007; 106: 439-451
        • Zablotska L.
        • Neugut A.
        Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma.
        Cancer. 2003; 97: 1404-1411
        • Deutsch M.
        • Land S.
        • Begovic M.
        • et al.
        The incidence of lung carcinoma after surgery for breast cancer with and without post-operative radiotherapy.
        Cancer. 2003; 98: 1362-1368
        • Harvey E.B.
        • Brinton L.A.
        Second cancer following cancer of the breast in Connecticut, 1935–82.
        Natl Cancer Inst Monogr. 1985; 68: 99-112
        • Huang J.
        • Mackillop W.
        Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma.
        Cancer. 2001; 92: 172-180
      12. Le Pogam MA, Rubino C, Diallo I, et al. Radiation dose fractionation and second cancer risks after breast cancer treatment. Rad Prot Dosimetry, in press.

        • Mellenkijaer L.
        • Frils S.
        • Olsen S.H.
        • et al.
        Risk of second cancers among women with breast cancer.
        Int J Cancer. 2006; 118: 2285-2292
        • Obedian E.
        • Fischer D.
        • Haffty B.
        Second malignancies after treatment of early-stage breast cancer: Lumpectomy and radiation therapy versus mastectomy.
        J Clin Oncol. 2000; 18: 2406-2412
        • Prochazka M.
        • Hall P.
        • Gagliardi F.
        • et al.
        Ionizing radiation and tobacco use increases the risk of a subsequent lung carcinoma in women with breast cancer.
        J Clin Oncol. 2005; 23: 7467-7474
        • Neugut A.I.
        • Murray T.
        • Santos J.
        • et al.
        Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers.
        Cancer. 1994; 73: 1615-1620
        • Rubino C.
        • Shamsaldin A.
        • Lê M.G.
        • et al.
        Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment.
        Breast Cancer Res Treat. 2005; 89: 277-288
        • Preston D.L.
        • Mattsson A.
        • Holmberg E.
        • et al.
        Radiation effects on breast cancer risk: a pooled analysis of eight cohorts.
        Radiat Res. 2002; 158: 666
        • Sedetzki S.
        • Calderon-Margalt R.
        • Peretz C.
        • et al.
        Second primary breast and thyroid cancers.
        Cancer Causes control. 2003; 14: 367-375
        • Lundell M.
        • Mattsson A.
        • Hakulinen T.
        • Holm L.E.
        Breast cancer after radiotherapy for skin hemagioma in infancy.
        Radiat Res. 1996; 145: 225-230
        • Brenner D.
        • Curtis R.
        • Hall E.
        • Ron E.
        Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.
        Cancer. 2000; 88: 398-406
        • Kendal W.S.
        • Eapen L.
        • Macrae R.
        • et al.
        Prostatic irradiation is not associated with any measurable increase in the risk of subsequent rectal cancer.
        Int J Radiat Oncol Biol Phys. 2006; 65: 637-639
        • Liauw S.L.
        • Sylvester J.E.
        • Morris C.G.
        • et al.
        Second malignancies after prostate brachytherapy: incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up.
        Int J Radiat Oncol Biol Phys. 2006; 66: 669-673
        • Moon K.
        • Stukenborg G.J.
        • Hein S.
        • Theodorescu D.
        Cancer incidence after localized therapy for prostate.
        Cancer. 2006; 107: 991-998
        • Pickles T.
        • Phillips N.
        The risk of second malignancy in men with prostate cancer treated with or without radiation in British Columbia. 1984–2000.
        Radiother Oncol. 2002; 65: 145-151
        • Brown A.P.
        • Chen J.
        • Hitchcock Y.J.
        • et al.
        The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer.
        J Clin Endocrinol Metab. 2008; 93: 504-515
        • Canchola A.S.
        • Horn-Ross P.L.
        • Purdie D.M.
        Risk of second primary malignancies in women with papillary thyroid cancer.
        Am J Epidemiol. 2006; 163: 521-527
        • Chuang S.C.
        • Hashiba M.
        • Yu G.P.
        • Le A.D.
        • et al.
        Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers.
        Cancer Lett. 2006; 218: 42-52
        • Sandeep T.C.
        • Strachan M.W.J.
        • Reynolds R.M.
        • et al.
        Second primary cancers in thyroid patients: multinational record linkage study.
        J Clin Endocrinol. 2006; 91: 1819-1825
        • Rubino C.
        • de Vathaire F.
        • Dottorini M.E.
        • et al.
        Second primary malignancies in thyroid cancer patients.
        Brit J Cancer. 2003; 89: 1638-1644
        • Rubino C.
        • Adjadj E.
        • Doyon F.
        • et al.
        Radiation exposure and familial aggregation of cancer as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma.
        Int J Radiat Oncol Biol Phys. 2003; 62: 1084-1089
        • Franklyn J.A.
        • Maisonneuve L.
        • Sheppard M.
        • Betteridge T.
        • Boyle P.
        Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population based study.
        Lancet. 1999; 353: 2111-2115
        • Read Jr., C.H.
        • Tansey M.J.
        • Menda Y.
        A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves’ patients.
        J Clin Endocrinol Metab. 2004; 89: 4229-4233
        • de Vathaire F.
        • Fragu P.
        • François P.
        • et al.
        Long term effects on the thyroid of radiation for skin angiomas in childhood.
        Radiation Res. 1994; 133: 381-386
        • de Vathaire F.
        • Hawkins M.
        • Campbell S.
        • et al.
        Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment.
        Br J Cancer. 1999; 79: 1884-1893
        • Dickman P.W.
        • Holm L.E.
        • Lundell G.R.
        • et al.
        Thyroid cancer risk after thyroid examination with 131I: a population based cohort study in Sweden.
        Int J Cancer. 2003; 106: 580-587
        • Schneider A.B.
        • Sarne D.H.
        Long-term risks for thyroid cancer and other neoplasms after exposure to radiation.
        Nat Clin Pract Endocrinol Metab. 2005; 1: 82-91
        • Scott B.
        Risk of thyroid cancer after exposure to 131I in childhood. Response Cardis E, Kesminienne A.
        J Nat Cancer Inst. 2006; 98: 561
        • Detours V.
        • Delys L.
        • Libert F.
        • et al.
        Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers.
        Br J Cancer. 2007; 97: 818-825
        • Travis L.B.
        • Curtis R.
        • Storm H.
        • et al.
        Risk of second malignant neoplasms among long-term survivors of testicular cancer.
        J Natl Cancer Inst. 1997; 89: 1429-1439
        • Travis L.B.
        • Andersson M.
        • Gospodarowicz M.
        • et al.
        Treatment-associated leukaemia following testicular cancer.
        J Natl Cancer Inst. 2000; 92: 1165-1171
        • Zagars G.
        • Ballo M.
        • Lee A.
        • Strom S.
        Mortality after cure of testicular seminoma.
        J Clin Oncol. 2004; 22: 585-588
        • Travis L.B.
        • Curtis R.E.
        • Boice Jr., J.D.
        • et al.
        Second malignant neoplasms among long-term survivors of ovarian cancer.
        Cancer Res. 1996; 56: 1564-1570
        • Tubiana M.
        Late mortality in Hodgkin’s disease: can we reduce it?.
        Ann Oncol. 2002; 13: 5-9
      13. Somers R, Henry-Amar M, Meerwald JK, et al., editors. Treatment strategy in Hodgkin’s disease. Workshop Paris, July 1989,vol. 196. London Paris: John Libbey. Eurotext; 1990.

        • Tubiana M.
        • Henry-Amar M.
        • Carde P.
        • et al.
        Toward comprehensive management tailored to prognostic factors of patients with clinical stages of I and II in Hodgkin’s disease. The EORTC Lymphoma Group controlled clinical trials: 1964–1987.
        Blood. 1989; 73: 47-56
        • Carde P.
        • Hagenbeck A.
        • Hayat M.
        • et al.
        Clinical staging versus laparatomy with MOPP versus ABVD in early stages Hodkin’s disease: the H6 twin randomized trials from the EORTC lymphoma cooperation group.
        J Clin Oncol. 1993; 11: 2258-2272
        • Tubiana M.
        • Henry-Amar M.
        • Hayat M.
        • et al.
        Long-term results of the EORTC randomized study of irradiation and vinblastine in clinical stages I and II of Hodgkin’s disease.
        Eur J Cancer. 1979; 15: 645-657
        • Schonfeld S.J.
        • Gilbert E.S.
        • Dores G.M.
        • et al.
        Accute myeloid leukaemia following Hodgkin lymphoma: a population based study of 35,511 patients.
        J Natl Cancer Inst. 2006; 98: 215-218
        • Travis L.B.
        • Hill D.
        • Dores G.M.
        • et al.
        Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma.
        J Nat Cancer Inst. 2005; 97: 1428-1437
        • Bhatia S.
        • Robison L.L.
        • Oberlin O.
        • et al.
        Breast cancer and other second neoplasms after childhood Hodgkin’s disease.
        N Engl J Med. 1996; 334: 745-751
        • Hodgson D.C.
        • Gilbert E.S.
        • Dores G.M.
        • et al.
        Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma.
        J Clin Oncol. 2007; 25: 1489-1497
        • Dores G.M.
        • Metayer C.
        • Curtis R.E.
        • et al.
        Second malignant neoplasms among long-term survivors of Hodgkin’s disease: a population-based evaluation over 25 years.
        J Clin Oncol. 2002; 20: 3484-3494
        • Foss Abrahamsen A.
        • Andersen A.
        • Nome O.
        • et al.
        Long-term risk of second malignancy after treatment of Hodgkin’s disease: the influence of treatment, age and follow-up time.
        Ann Oncol. 2002; 13: 1786-1791
        • Dietrich P.Y.
        • Henry-Amar M.
        • Cosset J.M.
        • et al.
        Second primary cancers in patients continuously disease-free from Hodgkin’s disease: a protective role for the spleen?.
        Blood. 1994; 84: 1209-1215
        • M’Kacher R.
        • Bennaceur-Griscelli A.
        • Girinsky T.
        • et al.
        Telomere shortening and associated chromosomal instability in peripheral blood lymphocytes of patients with Hodgkin’s lymphoma prior to any treatment and predictive of second cancers.
        Int J Radiat Oncol Biol Phys. 2007; 68: 465-471
        • Gilbert E.
        • Stovall M.
        • Gospodarowicz M.
        • et al.
        Lung cancer after treatment of Hodgkin’s disease: focus on radiation effects.
        Radiat Res. 2003; 159: 161-173
        • Henry-Amar M.
        Second cancer after the treatment for Hodgkin’s disease: a report from the International Database on Hodgkin’s Disease.
        Ann Oncol. 1992; 3: 117-128
        • Koh E.J.
        • Tran T.H.
        • Heydarian M.
        • et al.
        A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk.
        Radiation Oncol. 2007; 2: 13
        • Mauch P.M.
        • Kalish L.A.
        • Marcus K.C.
        • et al.
        Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin’s disease: long-term analysis of risk factors and outcome.
        Blood. 1996; 87: 3625-3632
        • Swerdlow A.J.
        • Barber J.A.
        • Hudson G.V.
        • et al.
        Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment.
        J Clin Oncol. 2000; 18: 498-509
        • Wolden S.L.
        • Lamborn K.R.
        • Cleary S.F.
        • et al.
        Second cancers following pediatric Hodgkin’s disease.
        J Clin Oncol. 1998; 16: 536-544
        • Green D.M.
        • Hyland A.
        • Barcos M.P.
        • et al.
        Second malignant neoplasms after treatment for Hodgkin’s disease in childhood or adolescence.
        J Clin Oncol. 2000; 18: 1492-1499
        • Guibout C.
        • Adjadj E.
        • Rubino C.
        Malignant breast tumors after radiotherapy for a first cancer during childhood.
        J Clin Oncol. 2005; 23: 197-204
        • Guérin S.
        • Guibout C.
        • Shamsaldin A.
        • et al.
        Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: a case-control study.
        Int J Cancer. 2007; 120: 96-102
        • Neglia J.P.
        • Friedman D.L.
        • Yasui Y.
        • et al.
        Second malignant neoplasms in five-year survivors of childhood cancer: Childhood cancer survivor study.
        J Natl Cancer Inst. 2001; 93: 618-629
        • Garwicz S.
        • Anderson H.
        • Olsen J.H.
        • et al.
        Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the 5 Nordic countries. The Nordic Society for Pediatric Hematology and Oncology. The association of the Nordic Cancer Registries.
        Int J Cancer. 2000; 88: 672-678
        • Neglia J.P.
        • Robison L.L.
        • Stovall M.
        • et al.
        New primary neoplasms of the central nervous system in survivors of childhood cancers. A report from the childhood cancer survivor study.
        J Natl Cancer Inst. 2006; 98: 1528-1537
        • Bassal M.
        • Mertens A.C.
        • Taylor L.
        • et al.
        Risk of selected subsequent carcinomas in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
        J Clin Oncol. 2006; 24: 476-483
        • Kleinerman R.A.
        Cancer risks following diagnosis and therapeutic radiation exposure in children.
        Pediatr Radiol. 2006; 36: 121-125
        • Sigurdson A.J.
        • Ronchers C.M.
        • Mertens A.C.
        • et al.
        Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study.
        Lancet. 2005; 365: 2014-2023
        • Perkins J.L.
        • Liu Y.
        • Mitby P.A.
        • et al.
        Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the childhood cancer survivor study.
        J Clin Oncol. 2005; 23: 3733-3741
        • Henderson T.O.
        • Whitton J.
        • Stovall M.
        • et al.
        Secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study.
        J Natl Cancer Inst. 2007; 99: 300-308
        • Bhatia S.
        • Landier W.
        Evaluating survivors of pediatric cancer.
        Cancer J. 2005; 11: 340-354
        • Guérin S.
        • Dupuy A.
        • Anderson H.
        • et al.
        Radiation dose as a risk factor for malignant melanoma following childhood cancer.
        Eur J Cancer. 2003; 39: 2379-2386
        • Jenkinson H.C.
        • Hawkins M.M.
        • Stiller C.A.
        • et al.
        Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain.
        Br J Cancer. 2004; 91: 1905-1910
        • Haddy N.
        • Le Deley M.C.
        • Samand A.
        • et al.
        Role of radiotherapy and chemotherapy in the risk of secondary leukaemia after a solid tumour in childhood.
        Eur J Cancer. 2006; 42: 2757-2764
        • Guérin S.
        • Hawkins M.
        • Shamsaldin A.
        • et al.
        Treatment-adjusted predisposition to second malignant neoplasms after a solid cancer in childhood: a case-controlled study.
        J Clin Oncol. 2007; 25: 2833-2839
        • Diallo I.
        • Lamon A.
        • Shamsaldin A.
        • Grimaud E.
        • de Vathaire F.
        • Chavaudra J.
        Estimation of the radiation dose delivered to any point outside the target volume per patient treated with external beam radiotherapy.
        Radiother Oncol. 1996; 38: 269-271
        • Kuttesch Jr., J.F.
        • Wexler L.H.
        • Marcus R.B.
        • et al.
        Second malignancies after Ewing’s sarcoma: radiation dose-dependency of secondary sarcomas.
        J Clin Oncol. 1996; 14: 2818-2825
        • Sadetzki S.
        • Flint-Richter P.
        • Ben-Tal T.
        • Nass D.
        Radiation-induced meningioma: a descriptive study of 253 cases.
        J Neurosurg. 2002; 97: 1078-1082
        • Minniti G.
        • Traish D.
        • Ashley S.
        • et al.
        Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years.
        J Clin Endocrinol Metab. 2005; 90: 800-804
        • Darby S.
        • Reeves G.
        • Key T.
        • Doll R.
        • Stovall M.
        Mortality in a cohort of women given X-ray therapy for metropathia haemorrhagica.
        Int J Cancer. 1994; 56: 793-801
        • Carr Z.A.
        • Kleinerman R.A.
        • Stovall M.
        • et al.
        Malignant neoplasms after radiation therapy for peptic ulcer.
        Radiat Res. 2002; 157: 668-677
        • Nguyen F.
        • Rubino C.
        • Guerin S.
        • et al.
        Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields.
        Int J Radiat Oncol Biol Phys. 2008; 70: 908-915
        • Tanooka H.
        Threshold dose-response in radiation carcinogenesis: an approach from chronic beta-irradiation experiments and a review of non tumour doses.
        Int J Radiat Biol. 2001; 77: 541-551
        • Wood D.H.
        Long-term mortality and cancer risk in irradiated rhesus monkeys.
        Radiat Res. 1991; 126: 132-140
        • Boukheris H.
        • Rubino C.
        • Arriagada R.
        • et al.
        Long-term mortality in a cohort study of 6,800 French breast cancer patients treated between 1954 and 1983.
        Acta Oncol. 2008; 47: 1122-1132
        • Xu X.G.
        • Bednarz B.
        • Paganetti H.
        A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction.
        Phys Med Biol. 2008; 53: R193-R241
        • Little M.P.
        Comparisons of the risk of cancer incidence and mortality following radiation therapy for benign or malignant disease with cancer risks observed in the Japanese A-bomb survivors.
        Int J Radiat Biol. 2000; 77: 431-464
        • Schneider U.
        • Walsh L.
        Cancer risk estimates from combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy.
        Radiat Environ Biophys. 2008; 47: 253-263
        • Miller A.B.
        • Howe G.R.
        • Sherman G.J.
        • et al.
        Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis.
        N Engl J Med. 1989; 321: 1285-1289
        • Boice J.D.
        • Preston D.
        • Davis F.G.
        • Monson R.R.
        Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts.
        Radiat Res. 1991; 125: 214-222
        • Doody M.M.
        • Lonstein J.E.
        • Stovall M.
        • et al.
        U.S. Scoliosis Cohort Study Collaborators. Breast cancer mortality following diagnostic X-rays: Findings from the U.S. Scoliosis Cohort Study.
        Spine. 2000; 25: 2052-2063
        • Franco N.
        • Lamartine J.
        • Frouin V.
        • et al.
        Low-dose exposure to γ rays induces specific gene regulations in normal human keratinocytes.
        Radiat Res. 2005; 163: 623-635
        • Sokolov M.V.
        • Smirnova N.A.
        • Camerini-Otero R.D.
        • Neumann R.D.
        • Panyutin I.G.
        Microarray analysis of differentially expressed genes after exposure of normal human fibroblasts to ionizing radiation from an external source and from DNA-incorporated iodine-125 radionuclide.
        Gene. 2000; 382: 47-56
        • Amundson S.A.
        • Lee R.A.
        • Koch-Paiz C.A.
        • et al.
        Differential responses of stress genes to low dose-rate gamma irradiation.
        Mol Cancer Res. 2003; 1: 445-452
        • Rosso S.
        • Zanetti R.
        • Martinez C.
        • et al.
        The multicenter South European study Helios, II – different sun exposure patterns in the etiology of basal-cell and squamous-cell carcinomag of the skin.
        Brit J Cancer. 1996; 73: 1447-1454
        • Vilenchik M.M.
        • Knudson A.G.
        Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates.
        Proc Natl Acad Sci USA. 2000; 97: 5381-5386
        • Vilenchik M.M.
        • Knudson A.G.
        Endogenous DNA double-strand break production, fidelity of repair and induction of cancer.
        Proc Natl Acad Sc USA. 2003; 103: 17874-17875
        • Loucas B.D.
        • Eberle R.
        • Bailey S.M.
        • Cornforth M.N.
        Influence of dose rate on the induction of simple and complex chromosome exchanges by gamma rays.
        Radiat Res. 2004; 162: 339-349
        • Rothkamm K.
        • Löbrich M.
        Evidence for a lack of DNA double-strand break repair in Human cells exposed to very low X-ray doses.
        Proc Natl Acad Sci USA. 2003; 100: 5057-5062
        • Yamamoto O.
        • Seyama T.
        • Ito A.
        • Fujimoto N.
        Oral administration of tritiated water (THO) in mouse. III: Low dose-rate irradiation and threshold dose-rate for radiation risk.
        Int J Radiat Biol. 1998; 73: 535-541
        • Paganetti H.
        Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy.
        Int J Radiat Oncol Biol Phys. 2005; 63: 892-900
        • Elmore E.
        • Lao X.-Y.
        • Kapadia R.
        • Redpath J.L.
        The effect of dose rate on radiation-induced neoplastic transformation in vitro by low doses of low-LET radiation.
        Radiat Res. 2006; 166: 832-838
        • Dikomey E.
        • Brammer I.
        Relationship between cellular radiosensitivity and non-repaired double-strand breaks studied for different growth states, dose rates and plating conditions in a normal fibroblast line.
        Int J Radiat Biol. 2000; 76: 773-781
        • Abdel-Wahab M.
        • Reis I.M.
        • Hamilton K.
        Second primary cancer after radiotherapy for prostate cancer – A SEER analysis of brachytherapy versus external beam radiotherapy.
        Int J Radiat Oncol Biol Phys. 2008; 72: 58-68
        • Pierquin B.
        • Tubiana M.
        • Pan C.
        • Lagrange J.L.
        • Calitchi E.
        • Otmezguine Y.
        Long-term results of breast cancer irradiation treatment with low-dose-rate external irradiation.
        Int J Radiat Oncol Biol Phys. 2007; 67: 117-121
        • Cairns J.
        Somatic stem cells and the kinetics of mutagenesis and carcinogenesis.
        Proc Natl Acad Sci USA. 2002; 99: 10567-10570
        • Hall E.J.
        • Cheng-Shie W.
        Radiation-induced second cancers: the impact of 3D-CRT and IMRT.
        Int J Radiat Oncol Biol Phys. 2003; 56: 83-88
        • Hall E.J.
        Intensity modulated radiation therapy, protons, and the risk of second cancers.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1-7
        • Kry S.
        • Salehpour M.
        • Followill D.S.
        • et al.
        The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy.
        Int J Radiat Oncol Biol Phys. 2005; 62: 1195-1203
        • Kry S.F.
        • Followill D.
        • White R.A.
        • et al.
        Uncertainty of calculated risk estimates for secondary malignancies after radiotherapy.
        Int J Radiat Oncol Biol Phys. 2007; 68: 1265-1271
        • Miller R.C.
        • Randers-Pehrson G.
        • Geand C.R.
        • Hall E.
        • Brenner D.J.
        The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei.
        Proc Natl Acad Sci USA. 1999; 96: 19-22
        • Aoyama H.
        • Westerly D.C.
        • Mackie T.R.
        • et al.
        Integral radiation dose to normal structures with conformal external beam radiation.
        Int J Radiat Oncol Biol Phys. 2006; 64: 962-967
        • François P.
        • Beurtheret C.
        • Dutreix A.
        Calculation of the dose delivered to organs outside the radiation beams.
        Med Phys. 1988; 15: 879-883
        • Kry S.F.
        • Titt U.
        • Followill D.
        • et al.
        A Monte Carlo model for out-of-field dose calculation from high-energy photon therapy.
        Med Phys. 2007; 34: 3489-3499
        • Van der Giessen P.H.
        • Bierhuizen H.W.
        Comparison of measured and calculated peripheral doses in patients undergoing radiation therapy.
        Radiother Oncol. 1997; 42: 265-270
        • Rijkee A.G.
        • Zoetelief J.
        • Raaijmakers C.P.
        • et al.
        Assessment of induction of secondary tumours due to various radiotherapy modalities.
        Radiat Prot Dosimetry. 2006; 118: 219-226
        • Svahn-Tapper G.
        • Garwicz S.
        • Anderson H.
        • et al.
        Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: a population-based case-control study in the five Nordic countries.
        Acta Oncol. 2006; 45: 438-448
        • Varma G.
        • Varma R.
        • Huang H.
        • et al.
        Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.
        Br J Cancer. 2005; 93: 699-708
        • Koscielny S.
        • Tubiana M.
        The link between local recurrence and distant metastases in human breast cancer.
        Int J Rad Oncol Biol Phys. 1999; 45: 245-246
        • Tubiana M.
        • Koscielny S.
        The natural history of breast cancer and the link between local recurrence and distant metastases: implications for therapy.
        Rep Pract Oncol Radiother. 2001; 6: 181-195
        • Fisher B.
        • Anderson S.
        • Bryant J.
        • et al.
        Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
        N Engl J Med. 2002; 347: 1233-1241
        • Belkacemi Y.
        • Chauvet M.P.
        • Giard S.
        • et al.
        Partial breast irradiation: high dose rate preoperative brachytherapy technique using the MommoSite.
        Cancer Radiother. 2003; 7: 129-136
        • Formenti S.C.
        • Truong M.T.
        • Goldberg J.D.
        • et al.
        Prone accelerated partial breast irradiation after breast-conserving surgery: preliminary clinical results and dose–volume histogram analysis.
        Int J Radiat Oncol Biol Phys. 2004; 60: 493-504
        • Fogliata A.
        • Nicolini G.
        • Alber M.
        • et al.
        IMRT for breast. A planning study.
        Radiother Oncol. 2005; 76: 300-310
        • Hughes K.S.
        • Schnaper L.A.
        • Berry D.
        • et al.
        Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.
        N Engl J Med. 2004; 351: 971-977
        • Ott O.J.
        • Hildebrandt G.
        • Pötter R.
        • et al.
        Accelerated partial breast irradiation with multi-catheter brachytherapy: local control, side effects and cosmetic outcome for 274 patients. Results of the German–Austrian multicentre trial.
        Radiother Oncol. 2007; 82: 281-286
        • Petersen R.P.
        • Truong P.T.
        • Kader H.A.
        • et al.
        Target volume delineation for partial breast radiotherapy planning: clinical characteristics associated with low interobserver concordance.
        Int J Radiat Oncol Biol Phys. 2007; 69: 41-48
        • Polgar C.
        • Fodor J.
        • Major T.
        • et al.
        Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma- 5-year results of a randomized trial.
        Int J Radiat Oncol Biol Phys. 2007; 69: 694-702
        • Taghian A.G.
        • Kozak K.R.
        • Katz A.
        • et al.
        Accelerated partial breast irradiation (APBI) using protons for patients with early-stage breast cancer: a comparison to 3D conformal photon/electrons based treatment.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1404-1410
        • Veronesi U.
        • Gatti G.
        • Luini A.
        • et al.
        Intraoperative radiation therapy for breast cancer: technical notes.
        Breast J. 2003; 9: 106-112
        • Vicini F.A.
        • Kestin L.
        • Chen P.
        • et al.
        Long-term efficacy and patterns of failure after accelerated partial breast irradiation: a molecular assay-based clonality evaluation.
        Int J Radiat Onco Biol Phys. 2003; 68: 341-346
        • Breckow J.
        Linear-no-threshold is a radiation-protection standard rather than a mechanistic effect model.
        Radiat Environ Biophys. 2006; 44: 257-260
        • Ron E.
        Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident.
        Health Phys. 2007; 93: 502-511
        • Tronko M.D.
        • Howe G.R.
        • Boddanova T.I.
        • et al.
        A cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: thyroid cancer in Ukraine detected during first screening.
        J Natl Cancer Inst. 2006; 98: 897-903
        • Euvrard S.
        • Kanitakis J.
        • Claudis D.
        Skin cancers after organ transplantation.
        N Engl J Med. 2003; 348: 1681-1691
        • Little M.P.
        • Muirhead C.R.
        Evidence for cuvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors.
        Int J Radiat Biol. 1996; 70: 83-94
        • Little M.P.
        • Muirhead C.R.
        Derivation of low dose extrapolation factors from analysis of the curvature in the cancer incidence dose response in Japanese atomic bomb survivors.
        Int J Radiat Biol. 2000; 76: 939-953
        • Doll R.
        • Wakeford R.
        Risk of childhood cancer from fetal irradiation.
        Br J Radiol. 1997; 70: 130-139
        • Naumburg E.
        • Bellocco R.
        • Cnattingius S.
        • et al.
        Intrauterine exposure to diagnostic of X rays and risk of childhood leukemia subtypes.
        Radiat Res. 2002; 156: 718-723
        • Shu X.O.
        • Potter J.D.
        • Linet M.S.
        • et al.
        Diagnostic X rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia by immunophenotype.
        Cancer Epidemiol Biomarkers Prevention. 2002; 11: 177-185
        • Rodvall Y.
        • Hrubec Z.
        • Pershagen G.
        • et al.
        Childhood cancer among Swedish twins.
        Cancer Causes Control. 1992; 3: 527-532
        • Delongchamp R.R.
        • Mabushi K.
        • Yasuhiko Y.
        • et al.
        Cancer mortality among atomic bomb survivors exposed in utero or as young children.
        Radiat Res. 1997; 147: 385-395
      14. IARC. Monograph on the evaluation of carcinogenic risks to humans. Vol. 75, Ionizing radiation, part I, X and gamma radiation and neutrons. IARC, Lyon; 2000.

        • Berrington A.
        • Darby S.
        Risk of cancer from diagnostic X-rays, estimates for the UK and 14 other countries.
        Lancet. 2004; 363: 345-351
        • Brenner D.J.
        • Hall E.J.
        Computed tomography – an increasing source of radiation exposure.
        N Engl J Med. 2007; 357: 2277-2284
        • Tubiana M.
        • Aurengo A.
        • Masse A.J.
        • Valleron A.J.
        Risk of cancer from diagnostic X-rays.
        The Lancet. 2004; 363: 1908
        • Scott B.
        • Sanders C.
        • Mitchel R.E.J.
        • Borcham D.J.
        CT scans may reduce rather than increase the risk of cancer.
        J. Am. Phys Surgeons. 2008; 13: 8-11
        • Stovall M.
        • Smith S.A.
        • Langholz B.M.
        • et al.
        Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the Wecare Study.
        Int J Radiat Oncol Biol Phys. 2008; 72: 1021-1030