Radiotherapy & Oncology
Volume 91, Issue 1 , Pages 4-15 , April 2009

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

  • Maurice Tubiana

      Affiliations

    • Corresponding Author InformationAddress: Institute Gustave Roussy, 94805 Villejuif, France. Fax: +33 1 42 86 38 85.

Received 11 July 2008 ,Revised 27 November 2008 ,Accepted 31 December 2008.

References 

  1. 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
  2. Trott KR. Second cancers after radiotherapy. In: van der Kogel, Joiner, editors. Basic clinical radiobiology. London: Hodder publ.; 2008 (in press).
  3. Dörr W, Herrmann T. Cancer induction by radiotherapy: dose dependence and spatial relationship to irradiated volume. J Radiol Prot. 2002;22:A117–A121
  4. 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
  5. Little MP, de Vathaire F, Charles MW, Hawkins MM, Muirhead CR. Variations with time and age in the risks of solid cancer incidence after radiation exposure in childhood. Stat Med. 1998;17:1341–1355
  6. Hall EJ, Giaccia A. radiobiology for the radiologist. Lippincott, Williams and Wilkins; 2006.
  7. Tubiana M, editor. Radiobiologie. Hermann/Médecine: Paris; 2008. 502 pages.
  8. 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
  9. 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
  10. 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
  11. Monier R, Tubiana M. Cancérogenèse: accroissement des connaissances et évolution des concepts. Oncologie. 2008;10:319–347
  12. Trott KR, 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
  13. Ames BN, Gold LS. Too many rodent carcinogens: mitogenesis increases mutagenesis. Science. 1990;249:970–971
  14. Ames BN, Gold LS. Environmental pollution, pesticides and the prevention of cancer: misconceptions. FASEB J. 1997;11:1041–1052
  15. 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.
  16. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction. Nat Rev/Cancer. 2006;6:107–116
  17. Cohen SM, Ellwein LB. Cell proliferation in carcinogenesis. Science. 1990;249:503–504
  18. Derksen PW, Tjin E, Meijer HP, et al. Illegitimate Wnt signaling promotes proliferation of multiple myeloma cells. Proc Natl Acad Sci USA. 2004;101:6122–6127
  19. Brash DE. Sunlight and the onset of skin cancer. Trends Genet. 1997;13:410–414
  20. Gould MN. Radiation initiation of carcinogenesis in vivo: a rare or common cellular event. In:  Boice JD,  Fraumeni JF editor. Radiation carcinogenesis: epidemiology and biological significance. New York: Raven Press; 1984;p. 347–358
  21. Kennedy AR, 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
  22. 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
  23. Campisi J. Senescent cells, tumor suppression and organism aging. Cell. 2005;120:513–522
  24. Schmitt CA. Cellular senescence and cancer treatment. Biochim Biophys Acta. 2007;1775:5–20
  25. Hoeijmakers JHJ. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411:366–374
  26. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85
  27. Averbeck D, Testard L, Boucher D. Changing views on ionizing radiation-induced cellular effects. Int J Low Radiat. 2006;3:117–134
  28. 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
  29. Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet. 2004;38:445–476
  30. Hickman JA. Apoptosis and tumorigenesis. Cur Opin Cell Biol. 2002;12:67–72
  31. Lyng FM, 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
  32. Portess DI, Bauer G, Hill MA, 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
  33. 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
  34. Collis SJ, Schwaninger JM, Ntambi AJ, et al. Evasion of early cellular response mechanisms following low level radiation induced DNA damage. J Biol Chem. 2004;279:49624–49632
  35. 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
  36. Hahn WC, Weinberg RA. Rules for making human tumor cells. New Engl J Med. 2002;347:1593–1603
  37. Weinberg RA. The biology of cancer. New York: Taylor & Francis; 2007.
  38. Barcellos-Hoff MH, Ravani SA. Irradiated gland mammary stroma promotes tumorogenic potential by unirradiated epithelial cells. Cancer Res. 2000;60:1254–1260
  39. Barcellos-Hoff MH. Integrative radiation carcinogenesis: interactions between cell and tissue responses to DNA damage. Sem Cancer Biol. 2005;15:138–148
  40. Radisky DC, Bissell MJ. Cancer. Respect thy neighbor!. Science. 2004;303:774–775
  41. Carnes BA, Groer PG, Kotec TJ. Radium dial workers: issues concerning dose response and modeling. Radiat Res. 1997;147:707–714
  42. Nyberg U, Nilsson B, Travis LB, et al. Cancer incidence among Swedish patients exposed to radioactive thorotrast: a forty-year follow-up survey. Radiat Res. 2002;157:419–425
  43. 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
  44. Wolff S. The adaptive response in radiobiology: evolving insights and implications. Environ Health Perspect. 1998;106:277–283
  45. Day TK, Zeng G, Hooker AM, 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
  46. Brenner DJ, Doll R, Goodhead DT, 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
  47. 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/>.
  48. Brenner DJ, Sachs RK. Estimating radiation-induced cancer risks at very low doses: rationale for using a linear no-threshold approach. Radiat Environ Biophys. 2006;44:253–256
  49. ICRP, Low-dose extrapolation of radiation-related cancer risk. Publication 99. International Commission on Radiological Protection. Elsevier, Amsterdam; 2006.
  50. 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
  51. Tubiana M. The linear no-threshold relationship and advances in our understanding of carcinogenesis. Int J Low Rad. 2008;5:173–204
  52. Tubiana M, Feinendegen L, Chichuan Y, Kaminski JM. The linear no-threshold relationship is inconsistent with radiobiological and experimental data. Radiology, in press.
  53. Charles MW. LNT – an apparent rather than a real controversy?. J Radiol Prot. 2006;26:325–329
  54. Wall BF, Kendall GM, Edwards AA, Bouffler S, Muirhead CR, Meara JR. What are the risks from medical X-rays and other low dose radiation?. Br J Radiol. 2006;79:285–294
  55. Belyakov OV, Folkard M, Mothersill C. Bystander induced differentiation. A major response to targeted irradiation of a urothelial explant model. Mutat Res. 2006;597:43–49
  56. Liu Z, Mothersill CE, McNeill FE, et al. A dose threshold for a medium transfer bystander effect for a human skin cell line. Radiat Res. 2006;166:19–23
  57. Morgan WF. 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
  58. Mothersill C, Seymour CB. Radiation-induced bystander effects and the DNA paradigm: an “out of field” perspective. Mutat Res. 2006;59:5–10
  59. Smith RW, Wang J, Bucking CP, Mothersill CE, Seymour CB. Evidence for a protective response by the gill proteome of rainbow trout exposed to X-ray induced bystander signals. Proteomics. 2007;7:4171–4180
  60. Leonard BE. Adaptive response and human benefit: part I – a microdosimetric dose dependent model. Int J Radiat Biol. 2007;83:115–131
  61. Leonard BE. Adaptive response: Part II – Modeling for dose rate and time influences. Int J Radiat Biol. 2007;83:395–408
  62. Streffer C. Bystander effects, adaptive response and genomic instability induced by prenatal irradiation. Rev Mutat Res. 2004;568:79–87
  63. 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
  64. Kadhim MA, Hill MA, Moore SR. Genomic instability and the role of radiation quality. Radiat Prot Dos. 2006;122:221–227
  65. 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
  66. Marples B, Wouters BG, Collis SJ, Chalmers AJ, Joiner MC. Low-dose hyper-radiosensitivity: a consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. Radiat Res. 2004;161:247–255
  67. 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
  68. 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
  69. Preston DL, Pierce DA, Shimizu Y, Cullings HM, Fujita S, Funamoto S, et al. Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates. Radiat Res. 2004;162:377–389
  70. Preston DL, Ron E, Tokuoka S, et al. Solid cancer incidence in atomic bomb survivors: 1958–1998. Radiat Res. 2007;168:1–64
  71. Chaturvedi AK, Engels EA, Gilbert ES, et al. Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk. J Natl Cancer Inst. 2007;99:1634–1643
  72. Kirova Y, Vilcoq J, Asselain B, et al. Radiation-induced sarcomas after radiotherapy for breast carcinoma. Cancer. 2005;104:856–863
  73. 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
  74. 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
  75. Cardis E, Howe G, Ron E, et al. Cancer consequences of the chernobyl accident: 20 years after. J Radiol Prot. 2006;26:127–140
  76. 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.
  77. 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
  78. ICRP Publication 60 – Ann. ICRP 21, Nos 1–3. Pergamon Press; 1991.
  79. ICRP Publication 103 – Ann. ICRP 37, Nos 2–4. Elsevier; 2007.
  80. Verkooijen RBT, Smit JWA, Romijn JA, Stokkel MP. 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
  81. Akolen LA, Glattre E. Second malignancies in thyroid cancer patients: a population-based survey of 3658 cases from Norway. Eur J Cancer. 1992;28:491–495
  82. Berthe E, Henry-Amar M, Michielo JJ, et al. Risk of second primary cancer following differentiated thyroid cancer. Eur J Nucl Med. 2004;31:685–691
  83. Chen AY, Levy L, Goepfert H, et al. The development of breast carcinoma in women with thyroid carcinoma. Cancer. 2001;92:225–231
  84. Kony SJ, 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
  85. Boice JD, Engholm G, Kleinerman RA, et al. Radiation dose and second cancer risk in patients treated for cancer of the cervix. Radiat Res. 1988;116:3–55
  86. 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
  87. Weiss H, Darby S, Doll R. Cancer mortality following X-ray treatment for ankylosing spondylitis. Int J Cancer. 1994;59:327–338
  88. 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
  89. Roychoudhuri R, Evans H, Robinson D, Moller H. Radiation-induced malignancies following radiotherapy for breast cancer. Brit J Cancer. 2004;91:568–572
  90. Darby SC, McGale P, Taylor CW, 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
  91. Brown LM, Chen BE, Pfeiffer RM, et al. Risk of second non-hematological malignancies among 376,825 breast cancer survivors. Breast Cancer Res Treat. 2007;106:439–451
  92. 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
  93. 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
  94. Harvey EB, Brinton LA. Second cancer following cancer of the breast in Connecticut, 1935–82. Natl Cancer Inst Monogr. 1985;68:99–112
  95. Huang J, Mackillop W. Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma. Cancer. 2001;92:172–180
  96. 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.
  97. Mellenkijaer L, Frils S, Olsen SH, et al. Risk of second cancers among women with breast cancer. Int J Cancer. 2006;118:2285–2292
  98. 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
  99. 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
  100. Neugut AI, Murray T, Santos J, et al. Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers. Cancer. 1994;73:1615–1620
  101. Rubino C, Shamsaldin A, Lê MG, et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat. 2005;89:277–288
  102. Preston DL, Mattsson A, Holmberg E, et al. Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiat Res. 2002;158:666
  103. Sedetzki S, Calderon-Margalt R, Peretz C, et al. Second primary breast and thyroid cancers. Cancer Causes control. 2003;14:367–375
  104. Lundell M, Mattsson A, Hakulinen T, Holm LE. Breast cancer after radiotherapy for skin hemagioma in infancy. Radiat Res. 1996;145:225–230
  105. Brenner D, Curtis R, Hall E, Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer. 2000;88:398–406
  106. Kendal WS, 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
  107. Liauw SL, Sylvester JE, Morris CG, 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
  108. Moon K, Stukenborg GJ, Hein S, Theodorescu D. Cancer incidence after localized therapy for prostate. Cancer. 2006;107:991–998
  109. 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
  110. Brown AP, Chen J, Hitchcock YJ, 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
  111. Canchola AS, Horn-Ross PL, Purdie DM. Risk of second primary malignancies in women with papillary thyroid cancer. Am J Epidemiol. 2006;163:521–527
  112. Chuang SC, Hashiba M, Yu GP, Le AD, et al. Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers. Cancer Lett. 2006;218:42–52
  113. Sandeep TC, Strachan MWJ, Reynolds RM, et al. Second primary cancers in thyroid patients: multinational record linkage study. J Clin Endocrinol. 2006;91:1819–1825
  114. Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thyroid cancer patients. Brit J Cancer. 2003;89:1638–1644
  115. 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
  116. Franklyn JA, 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
  117. Read CH, Tansey MJ, 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
  118. 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
  119. 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
  120. Dickman PW, Holm LE, Lundell GR, et al. Thyroid cancer risk after thyroid examination with 131I: a population based cohort study in Sweden. Int J Cancer. 2003;106:580–587
  121. Schneider AB, Sarne DH. Long-term risks for thyroid cancer and other neoplasms after exposure to radiation. Nat Clin Pract Endocrinol Metab. 2005;1:82–91
  122. Scott B. Risk of thyroid cancer after exposure to 131I in childhood. Response Cardis E, Kesminienne A. J Nat Cancer Inst. 2006;98:561
  123. 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
  124. Travis LB, 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
  125. Travis LB, Andersson M, Gospodarowicz M, et al. Treatment-associated leukaemia following testicular cancer. J Natl Cancer Inst. 2000;92:1165–1171
  126. Zagars G, Ballo M, Lee A, Strom S. Mortality after cure of testicular seminoma. J Clin Oncol. 2004;22:585–588
  127. Travis LB, Curtis RE, Boice JD, et al. Second malignant neoplasms among long-term survivors of ovarian cancer. Cancer Res. 1996;56:1564–1570
  128. Tubiana M. Late mortality in Hodgkin’s disease: can we reduce it?. Ann Oncol. 2002;13(suppl 1):5–9
  129. 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.
  130. 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
  131. 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
  132. 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
  133. Schonfeld SJ, Gilbert ES, Dores GM, et al. Accute myeloid leukaemia following Hodgkin lymphoma: a population based study of 35,511 patients. J Natl Cancer Inst. 2006;98:215–218
  134. Travis LB, Hill D, Dores GM, et al. Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J Nat Cancer Inst. 2005;97:1428–1437
  135. Bhatia S, Robison LL, Oberlin O, et al. Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med. 1996;334:745–751
  136. Hodgson DC, Gilbert ES, Dores GM, et al. Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma. J Clin Oncol. 2007;25:1489–1497
  137. Dores GM, Metayer C, Curtis RE, 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
  138. 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
  139. Dietrich PY, Henry-Amar M, Cosset JM, 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
  140. 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
  141. 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
  142. 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(suppl 4):117–128
  143. Koh EJ, Tran TH, 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
  144. Mauch PM, Kalish LA, Marcus KC, 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
  145. Swerdlow AJ, Barber JA, Hudson GV, 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
  146. Wolden SL, Lamborn KR, Cleary SF, et al. Second cancers following pediatric Hodgkin’s disease. J Clin Oncol. 1998;16:536–544
  147. Green DM, Hyland A, Barcos MP, et al. Second malignant neoplasms after treatment for Hodgkin’s disease in childhood or adolescence. J Clin Oncol. 2000;18:1492–1499
  148. Guibout C, Adjadj E, Rubino C. Malignant breast tumors after radiotherapy for a first cancer during childhood. J Clin Oncol. 2005;23:197–204
  149. 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
  150. Neglia JP, Friedman DL, 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
  151. Garwicz S, Anderson H, Olsen JH, 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
  152. Neglia JP, Robison LL, 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
  153. Bassal M, Mertens AC, 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
  154. Kleinerman RA. Cancer risks following diagnosis and therapeutic radiation exposure in children. Pediatr Radiol. 2006;36(suppl 14):121–125
  155. Sigurdson AJ, Ronchers CM, Mertens AC, 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
  156. Perkins JL, Liu Y, Mitby PA, 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
  157. Henderson TO, 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
  158. Bhatia S, Landier W. Evaluating survivors of pediatric cancer. Cancer J. 2005;11:340–354
  159. 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
  160. Jenkinson HC, Hawkins MM, Stiller CA, et al. Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain. Br J Cancer. 2004;91:1905–1910
  161. Haddy N, Le Deley MC, 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
  162. 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
  163. 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
  164. Kuttesch JF, Wexler LH, Marcus RB, et al. Second malignancies after Ewing’s sarcoma: radiation dose-dependency of secondary sarcomas. J Clin Oncol. 1996;14:2818–2825
  165. 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
  166. 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
  167. 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
  168. Carr ZA, Kleinerman RA, Stovall M, et al. Malignant neoplasms after radiation therapy for peptic ulcer. Radiat Res. 2002;157:668–677
  169. 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
  170. 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
  171. Wood DH. Long-term mortality and cancer risk in irradiated rhesus monkeys. Radiat Res. 1991;126:132–140
  172. 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
  173. Xu XG, 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
  174. Little MP. 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
  175. 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
  176. Miller AB, Howe GR, Sherman GJ, 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
  177. Boice JD, Preston D, Davis FG, Monson RR. Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat Res. 1991;125:214–222
  178. Doody MM, Lonstein JE, 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
  179. 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
  180. Sokolov MV, Smirnova NA, Camerini-Otero RD, Neumann RD, Panyutin IG. 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
  181. Amundson SA, Lee RA, Koch-Paiz CA, et al. Differential responses of stress genes to low dose-rate gamma irradiation. Mol Cancer Res. 2003;1:445–452
  182. 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
  183. Vilenchik MM, Knudson AG. Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates. Proc Natl Acad Sci USA. 2000;97:5381–5386
  184. Vilenchik MM, Knudson AG. Endogenous DNA double-strand break production, fidelity of repair and induction of cancer. Proc Natl Acad Sc USA. 2003;103:17874–17875
  185. Loucas BD, Eberle R, Bailey SM, Cornforth MN. Influence of dose rate on the induction of simple and complex chromosome exchanges by gamma rays. Radiat Res. 2004;162:339–349
  186. 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(9):5057–5062
  187. 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
  188. 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
  189. Elmore E, Lao X-Y, Kapadia R, Redpath JL. 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
  190. 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
  191. Abdel-Wahab M, Reis IM, 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
  192. Pierquin B, Tubiana M, Pan C, Lagrange JL, 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
  193. Cairns J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc Natl Acad Sci USA. 2002;99:10567–10570
  194. Hall EJ, Cheng-Shie W. Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys. 2003;56:83–88
  195. Hall EJ. Intensity modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65:1–7
  196. Kry S, Salehpour M, Followill DS, et al. The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2005;62:1195–1203
  197. Kry SF, Followill D, White RA, et al. Uncertainty of calculated risk estimates for secondary malignancies after radiotherapy. Int J Radiat Oncol Biol Phys. 2007;68:1265–1271
  198. Miller RC, Randers-Pehrson G, Geand CR, Hall E, Brenner DJ. The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei. Proc Natl Acad Sci USA. 1999;96:19–22
  199. Aoyama H, Westerly DC, Mackie TR, et al. Integral radiation dose to normal structures with conformal external beam radiation. Int J Radiat Oncol Biol Phys. 2006;64:962–967
  200. François P, Beurtheret C, Dutreix A. Calculation of the dose delivered to organs outside the radiation beams. Med Phys. 1988;15:879–883
  201. Kry SF, 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
  202. Van der Giessen PH, Bierhuizen HW. Comparison of measured and calculated peripheral doses in patients undergoing radiation therapy. Radiother Oncol. 1997;42:265–270
  203. Rijkee AG, Zoetelief J, Raaijmakers CP, et al. Assessment of induction of secondary tumours due to various radiotherapy modalities. Radiat Prot Dosimetry. 2006;118:219–226
  204. 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
  205. 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
  206. 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
  207. 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
  208. 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
  209. Belkacemi Y, Chauvet MP, Giard S, et al. Partial breast irradiation: high dose rate preoperative brachytherapy technique using the MommoSite. Cancer Radiother. 2003;7:129–136
  210. Formenti SC, Truong MT, Goldberg JD, 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
  211. Fogliata A, Nicolini G, Alber M, et al. IMRT for breast. A planning study. Radiother Oncol. 2005;76:300–310
  212. Hughes KS, Schnaper LA, 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
  213. Ott OJ, 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
  214. Petersen RP, Truong PT, Kader HA, 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
  215. 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
  216. Taghian AG, Kozak KR, 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
  217. Veronesi U, Gatti G, Luini A, et al. Intraoperative radiation therapy for breast cancer: technical notes. Breast J. 2003;9:106–112
  218. Vicini FA, 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
  219. Breckow J. Linear-no-threshold is a radiation-protection standard rather than a mechanistic effect model. Radiat Environ Biophys. 2006;44:257–260
  220. Ron E. Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident. Health Phys. 2007;93:502–511
  221. Tronko MD, Howe GR, Boddanova TI, 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
  222. Euvrard S, Kanitakis J, Claudis D. Skin cancers after organ transplantation. N Engl J Med. 2003;348:1681–1691
  223. Little MP, Muirhead CR. Evidence for cuvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors. Int J Radiat Biol. 1996;70:83–94
  224. Little MP, Muirhead CR. 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
  225. Doll R, Wakeford R. Risk of childhood cancer from fetal irradiation. Br J Radiol. 1997;70:130–139
  226. 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
  227. Shu XO, Potter JD, Linet MS, 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
  228. Rodvall Y, Hrubec Z, Pershagen G, et al. Childhood cancer among Swedish twins. Cancer Causes Control. 1992;3:527–532
  229. Delongchamp RR, 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
  230. 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.
  231. Berrington A, Darby S. Risk of cancer from diagnostic X-rays, estimates for the UK and 14 other countries. Lancet. 2004;363:345–351
  232. Brenner DJ, Hall EJ. Computed tomography – an increasing source of radiation exposure. N Engl J Med. 2007;357:2277–2284
  233. Tubiana M, Aurengo A, Masse AJ, Valleron AJ. Risk of cancer from diagnostic X-rays. The Lancet. 2004;363:1908
  234. Scott B, Sanders C, Mitchel REJ, Borcham DJ. CT scans may reduce rather than increase the risk of cancer. J. Am. Phys Surgeons. 2008;13:8–11
  235. Stovall M, Smith SA, Langholz BM, 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

PII: S0167-8140(09)00006-1

doi: 10.1016/j.radonc.2008.12.016

Radiotherapy & Oncology
Volume 91, Issue 1 , Pages 4-15 , April 2009

Article Tools