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A review on fetal dose in Radiotherapy: A historical to contemporary perspective

Published:December 23, 2022DOI:https://doi.org/10.1016/j.ejmp.2022.102513

      Highlights

      • Gy dose threshold for fetal dose to limit adverse effect of radiation.
      • Estimate fetal dose with Monte Carlo method or phantom measurement before treatment.
      • Shielding and dose reduction techniques to further reduce out-of-field dose.
      • Neutrons contribute most to fetal out-of-field dose in proton therapy.
      • Use of daily CBCT in IGRT for pregnant patient should be carefully considered.

      Abstract

      This paper aims to review on fetal dose in radiotherapy and extends and updates on a previous work1 to include proton therapy. Out-of-field doses, which are the doses received by regions outside of the treatment field, are unavoidable regardless of the treatment modalities used during radiotherapy. In the case of pregnant patients, fetal dose is a major concern as it has long been recognized that fetuses exposed to radiation have a higher probability of suffering from adverse effects such as anatomical malformations and even fetal death, especially when the 0.1 G y threshold is exceeded. In spite of the low occurrence of cancer during pregnancy, the radiotherapy team should be equipped with the necessary knowledge to deal with fetal dose. This is crucial so as to ensure that the fetus is adequately protected while not compromising the patient treatment outcomes. In this review paper, various aspects of fetal dose will be discussed ranging from biological, clinical to the physics aspects. Other than fetal dose resulting from conventional photon therapy, this paper will also extend the discussion to modern treatment modalities and techniques, namely proton therapy and image-guided radiotherapy, all of which have seen a significant increase in use in current radiotherapy. This review is expected to provide readers with a comprehensive understanding of fetal dose in radiotherapy, and to be fully aware of the steps to be taken in providing radiotherapy for pregnant patients.

      Keywords

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      References

        • Mazonakis M.
        • Damilakis J.
        Estimation and reduction of the radiation dose to the fetus from external-beam radiotherapy.
        Phys Med. 2017; 43: 148-152
        • Pavlidis N.A.
        Coexistence of pregnancy and malignancy.
        Oncologist. 2002; 7: 573https://doi.org/10.1634/theoncologist.7-6-573
        • Applegate K.E.
        • Findlay Ú.
        • Fraser L.
        • Kinsella Y.
        • Ainsbury L.
        • Bouffler S.
        Radiation exposures in pregnancy, health effects and risks to the embryo/foetus—information to inform the medical management of the pregnant patient.
        J Radiol Prot. 2021; 41: S522-S539
        • Stovall M.
        • Blackwell C.R.
        • Cundiff J.
        • Novack D.H.
        • Palta J.R.
        • Wagner L.K.
        • et al.
        Fetal dose from radiotherapy with photon beams: report of AAPM Radiation Therapy Committee Task Group No. 36.
        Med Phys. 1995; 22: 63-82
        • Kry S.F.
        • Bednarz B.
        • Howell R.M.
        • Dauer L.
        • Followill D.
        • Klein E.
        • et al.
        AAPM TG 158: measurement and calculation of doses outside the treated volume from external-beam radiation therapy.
        Med Phys. 2017; 44: e391-e429
        • Mayr N.A.
        • Wen B.-C.
        • Saw C.B.
        RADIATION THERAPY DURING PREGNANCY.
        Obstet Gynecol Clin N Am. 1998; 25: 301-321
        • Martin D.D.
        Review of radiation therapy in the pregnant cancer patient.
        Clin Obstet Gynecol. 2011; 54: 591-601
      1. Pregnancy and Medical Radiation; ICRP Publication 84. Annals of the ICRP 30, 1–43 (2000).

        • Michalet M.
        • Dejean C.
        • Schick U.
        • Durdux C.
        • Fourquet A.
        • Kirova Y.
        Radiotherapy and pregnancy.
        Cancer/Radiotherapie. 2022; 26: 417-423
      2. National Council on Radiation Protection and Measurements. & National Council on Radiation Protection and Measurements. Scientific Committee 4-4 on the Risks of Ionizing Radiation to the Developing Embryo, F. Preconception and prenatal radiation exposure: health effects and protective guidance. (2013).

        • Boué J.
        • Boué A.
        • Lazar P.
        RETROSPECTIVE AND PROSPECTIVE EPIDEMIOLOGICAL STUDIES OF 1500 KARYOTYPED SPONTANEOUS HUMAN ABORTIONS.
        Obstet Gynecol Surv. 1976; 31: 617-619
        • Wallch E.
        • Simpson J.L.
        Genes, chromosomes, and reproductive failure.
        Fertil Steril. 1980; 33: 107-116
        • Brent R.L.
        The effect of x-irradiation on rat embryos at the twelfth day of gestation.
        University of Rochester, 1955
      3. Konermann G. Postimplantation Defects in Development following Ionizing Irradiation. in 91–167 (1987). doi:10.1016/B978-0-12-035413-9.50007-8.

        • Konermann G.
        Mouse germ development following continuous Co60 gamma irradiation during blastogenesis, organogenesis and fetal period.
        Strahlentherapie. 1969; 137: 451-466
        • Russell L.B.
        • Russell W.L.
        The effects of radiation on the preim-plantation stages of the mouse embryo.
        Anat Res. 1950; 108: 521
        • Russell L.B.
        • Russell W.L.
        An analysis of the changing radiation response of the developing mouse embryo.
        J Cell Physiol Suppl. 1954; 43: 103-149
      4. RUSSELL LB, RUSSELL WL. Hazards to the embryo and fetus from ionizing radiation. in Proceedings of the International Conference on Peaceful Uses of Atomic Energy 175–178 (1956).

        • Wilson J.G.
        • Brent R.L.
        • Jordan H.C.
        Differentiation as a determinant of the reaction of rat embryos to X-irradiation.
        Exp Biol Med. 1953; 82: 67-70
        • Wilson J.G.
        • Jordan H.C.
        • Brent R.L.
        • Effects of irradiation on embryonic development. II.
        X-rays on the ninth day of gestation in the rat.
        Am J Anat. 1953; 92: 153-187
        • Rugh R.
        X-ray-Induced Teratogenesis in the mouse and its possible significance to man.
        Radiology. 1971; 99: 433-443
        • Wilson J.G.
        Differentiation and the reaction of rat embryos to radiation.
        J Cell Comp Physiol. 1954; 43: 11-37
      5. Wilson JG. Environment and birth defects. (1973).

        • Wilson J.G.
        • Karr J.W.
        Effects of irradiation on embryonic development. I. X-rays on the 10th day of gestation in the rat.
        Am J Anat. 1951; 88: 1-33
        • Wilson J.G.
        • Brent R.L.
        • Jordan H.C.
        Neoplasia induced in rat embryos by roentgen irradiation.
        Cancer Res. 1952; 12: 222-228
        • Brent R.L.
        Utilization of developmental basic science principles in the evaluation of reproductive risks from pre- and postconception environmental radiation exposures.
        Teratology. 1999; 59: 182-204
      6. Konermann G. Consequences of prenatal radiation exposure on perinatal and postnatal development. in Developmental Effects of Prenatal Irradiation 237–250 (1982).

        • Kato H.
        MORTALITY IN CHILDREN EXPOSED TO THE A-BOMBS WHILE IN UTERO, 1945-19691.
        Am J Epidemiol. 1971; 93: 435-442
        • Otake M.
        Threshold for radiation-related severe mental retardation in prenatally exposed A-bomb survivors: a re-analysis.
        Int J Radiat Biol. 1996; 70: 755-763
        • Blot W.J.
        • Miller R.W.
        Mental retardation following in utero exposure to the atomic bombs of Hiroshima and Nagasaki.
        Radiology. 1973; 106: 617-619
        • Miller R.W.
        Effects of prenatal exposure to ionizing radiation.
        Health Phys. 1990; 59: 57-61
        • Miller R.W.
        • Mulvihill J.J.
        Small head size after atomic irradiation.
        Teratology. 1976; 14: 355-357
        • Murphy D.P.
        The outcome of 625 pregnancies in women subjected to pelvic radium or roentgen irradiation.
        Am J Obstet Gynecol. 1929; 18: 179-187
        • Murphy D.P.
        • Shirlock M.E.
        • Doll E.A.
        Microcephaly following maternal pelvic irradiation for the interruption of pregnancy.
        Am J Roentgenol. 1942; 48: 356-359
        • Otake M.
        • Schull W.J.
        In utero exposure to A-bomb radiation and mental retardation; a reassessment.
        Br J Radiol. 1984; 57: 409-414
        • Otake M.
        • Schull W.J.
        Review: radiation-related brain damage and growth retardation among the prenatally exposed atomic bomb survivors.
        Int J Radiat Biol. 1998; 74: 159-171
        • Schull W.J.
        • Otake M.
        Cognitive function and prenatal exposure to ionizing radiation.
        Teratology. 1999; 59: 222-226
        • Wood J.W.
        • Keehn R.J.
        • Kawamoto S.
        • Johnson K.G.
        The growth and development of children exposed in utero to the atomic bombs in Hiroshima and Nagasaki.
        Am J Public Health Nation’s Health. 1967; 57: 1374-1380
        • Wood J.W.
        • Johnson K.G.
        • Omori Y.
        • Kawamoto S.
        • Keehn R.J.
        Mental retardation in children exposed in utero to the atomic bombs in Hiroshima and Nagasaki.
        Am J Public Health Nation’s Health. 1967; 57: 1381-1389
        • Yoshimaru H.
        • Otake M.
        • Schull W.J.
        • Funamoto S.
        Further observations on abnormal brain development caused by prenatal A-bomb exposure to ionizing radiation.
        Int J Radiat Biol. 1995; 67: 359-371
        • Dekaban A.S.
        Abnormalities in children exposed to x-radiation during various stages of gestation: tentative timetable of radiation injury to the human fetus. I.
        J Nucl Med. 1968; 9: 471-477
        • Doll E.A.
        • Murphy D.P.
        A CASE OF MICROCEPHALY FOLLOWING EMBRYONIC ROENTGEN IRRADIATION.
        Am J Psychiatry. 1930; 86: 871-878
        • Goldstein L.
        • Murphy D.P.
        Amenorrhea during serial roentgen exposures due to intervening pregnancy.
        Am J Obstet Gynecol. 1929; 18: 696-698
        • Goldstein L.
        • Murphy D.P.
        Microcephalic idiocy following radium therapy for uterine cancer during pregnancy.
        Am J Obstet Gynecol. 1929; 18: 189-195
        • Goldstein L.
        • Murphy D.P.
        Etiology of ill-health in children born after maternal pelvic irradiation. II. Defective children born after postconception pelvic irradiation.
        AJR Am J Roentgenol. 1929; 22: 322-331
        • Mayer M.D.
        • Harris W.
        • Wimpfheimer S.
        Therapeutic abortion by means of X-Ray**Read at a meeting of the New York Obstetrical Society, May 12, 1936.
        Am J Obstet Gynecol. 1936; 32: 945-957
        • Miller R.W.
        Discussion: severe mental retardation and cancer among atomic bomb survivors exposed in utero.
        Teratology. 1999; 59: 234-235
      7. Miller RW. Delayed radiation effects in atomic-bomb survivors. Major observations by the Atomic Bomb Casualty Commission are evaluated. Science (New York, N.Y.) 166, 569–74 (1969).

        • Greulich W.W.
        • Crismon C.S.
        • Turner M.L.
        • Greulich M.L.
        • Okumoto Y.
        The physical growth and development of children who survived the atomic bombing of Hiroshima or Nagasaki.
        J Pediatr. 1953; 43: 121-145
        • Nakashima E.
        • Fujiwara S.
        • Funamoto S.
        Effect of radiation dose on the height of atomic bomb survivors: a longitudinal study.
        Radiat Res. 2002; 158: 346-351
      8. Miller RW. EPIDEMIOLOGICAL CONCLUSIONS FROM RADIATION TOXICITY STUDIES. (1970).

        • Otake M.
        • Fujikoshi Y.
        • Schull W.J.
        • Izumi S.
        A longitudinal study of growth and development of stature among prenatally exposed atomic bomb survivors.
        Radiat Res. 1993; 134: 94-101
        • Otake M.
        • Fujikoshi Y.
        • Funamoto S.
        • Schull W.J.
        Evidence of radiation-induced reduction of height and body weight from repeated measurements of adults exposed in childhood to the atomic bombs.
        Radiat Res. 1994; 140: 112-122
        • Blot W.J.
        Growth and development following prenatal and childhood exposure to atomic radiation.
        J Radiat Res. 1975; 16: 82-88
        • Nakashima E.
        • Carter R.L.
        • Neriishi K.
        • Tanaka S.
        • Fun S.
        Height reduction among prenatal exposed atomic-bomb survivors.
        Health Phys. 1995; 68: 766-772
        • Rugh R.
        • Duhamel L.
        • Osborne A.W.
        • Varma A.
        Persistent stunting following x-irradiation of the fetus.
        Am J Anat. 1964; 115: 185-197
        • Tatsukawa Y.
        • Nakashima E.
        • Yamada M.
        • Funamoto S.
        • Hida A.
        • Akahoshi M.
        • et al.
        Cardiovascular disease risk among atomic bomb survivors exposed in utero, 1978–2003.
        Radiat Res. 2008; 170: 269-274
        • Imaizumi M.
        • Ashizawa K.
        • Neriishi K.
        • Akahoshi M.
        • Nakashima E.
        • Usa T.
        • et al.
        Thyroid diseases in atomic bomb survivors exposed in Utero.
        J Clin Endocrinol Metab. 2008; 93: 1641-1648
        • Ivanov E.P.
        • Tolochko G.V.
        • Shuvaeva L.P.
        • Ivanov V.E.
        • Iaroshevich R.F.
        • Becker S.
        • et al.
        Infant leukemia in Belarus after the Chernobyl accident.
        Radiat Environ Biophys. 1998; 37: 53-55
        • Delongchamp R.R.
        • Mabuchi K.
        • Yoshimoto Y.
        • Preston D.L.
        Cancer mortality among atomic bomb survivors exposed in utero or as young children, October 1950-May 1992.
        Radiat Res. 1997; 147: 385-395
        • Machado S.G.
        • Land C.E.
        • McKay F.W.
        Cancer mortality and radioactive fallout in southwestern Utah.
        Am J Epidemiol. 1987; 125: 44-61
        • Parkin D.M.
        • Clayton D.
        • Black R.J.
        • Masuyer E.
        • Friedl H.P.
        • Ivanov E.
        • et al.
        Childhood leukaemia in Europe after Chernobyl: 5 year follow-up.
        Br J Cancer. 1996; 73: 1006-1012
        • Darby S.C.
        • Doll R.
        Fallout, radiation doses near Dounreay, and childhood leukaemia.
        Br Med J (Clin Res Ed). 1987; 294: 603-607
        • Darby S.C.
        • Olsen J.H.
        • Doll R.
        • Thakrar B.
        • Brown P.D.
        • Storm H.H.
        • et al.
        Trends in childhood Leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.
        BMJ (Clinical Research Ed). 1992; 304: 1005-1009
        • Dockerty J.D.
        • Cox B.
        • Cockburn M.G.
        Childhood leukaemias in New Zealand: time trends and ethnic differences.
        Br J Cancer. 1996; 73: 1141-1147
        • Preston D.L.
        • Cullings H.
        • Suyama A.
        • Funamoto S.
        • Nishi N.
        • Soda M.
        • et al.
        Solid cancer incidence in atomic bomb survivors exposed in utero or as young children.
        JNCI: J Natl Cancer Inst. 2008; 100: 428-436
        • Ostroumova E.
        • Akleyev A.
        • Hall P.
        Infant mortality among offspring of individuals living in the radioactively contaminated Techa River Area, Southern Urals.
        Acta Medica Nagasakiensia. 2005; 50: S23-S28
        • Hatch M.
        • Brenner A.
        • Bogdanova T.
        • Derevyanko A.
        • Kuptsova N.
        • Likhtarev I.
        • et al.
        A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl Fallout.
        J Clin Endocrinol Metab. 2009; 94: 899-906
        • Donegan W.L.
        Breast cancer and pregnancy.
        Obstet Gynecol Surv. 1978; 33: 246-248https://doi.org/10.1097/00006254-197804000-00009
        • Knabben L.
        • Mueller M.D.
        Breast cancer and pregnancy.
        Horm Mol Biol Clin Invest. 2017; https://doi.org/10.1515/hmbci-2017-0026
        • Haba Y.
        • Twyman N.
        • Thomas S.J.
        • Overton C.
        • Dendy P.
        • Burnet N.G.
        Radiotherapy for glioma during pregnancy: fetal dose estimates, risk assessment and clinical management.
        Clin Oncol. 2004; 16: 210-214
        • Sharma D.S.
        • Jalali R.
        • Tambe C.M.
        • Animesh
        • Deshpande D.D.
        Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.
        Radiother Oncol. 2004; 70: 49-54
        • Yu C.
        • Jozsef G.
        • Apuzzo M.L.J.
        • MacPherson D.M.
        • Petrovich Z.
        • Kondziolka D.
        • et al.
        Fetal radiation doses for model C gamma knife radiosurgery.
        Neurosurgery. 2003; https://doi.org/10.1227/01.NEU.0000048479.23069.24
        • Magné N.
        • Marcié S.
        • Pignol J.-P.
        • Casagrande F.
        • Lagrange J.-L.
        Radiotherapy for a solitary brain metastasis during pregnancy: a method for reducing fetal dose.
        Br J Radiol. 2001; 74: 638-641
        • Sneed P.K.
        • Albright N.W.
        • Wara W.M.
        • Prados M.D.
        • Wilson C.B.
        Fetal dose estimates for radiotherapy of brain tumors during pregnancy.
        Int J Radiat Oncol Biol Phys. 1995; 32: 823-830
        • Pantelis E.
        • Antypas C.
        • Frassanito M.C.
        • Sideri L.
        • Salvara K.
        • Lekas L.
        • et al.
        Radiation dose to the fetus during CyberKnife radiosurgery for a brain tumor in pregnancy.
        Phys Med. 2016; 32: 237-241
        • Mazonakis M.
        • Damilakis J.
        • Theoharopoulos N.
        • Varveris H.
        • Gourtsoyiannis N.
        Brain radiotherapy during pregnancy: an analysis of conceptus dose using anthropomorphic phantoms.
        BJR. 1999; 72: 274-278
        • Podgorsak M.B.
        • Meiler R.J.
        • Kowal H.
        • Kishel S.P.
        • Orner J.B.
        Technical management of a pregnant patient undergoing radiation therapy to the head and neck.
        Med Dosim. 1999; 24: 121-128
        • Nuyttens J.J.
        • Prado K.L.
        • Jenrette J.M.
        • Williams T.E.
        Fetal dose during radiotherapy: clinical implementation and review of the literature.
        Cancer/Radiotherapie. 2002; 6: 352-357
        • Martinez Pineda W.J.
        • Calva Espinosa A.L.
        • Gonzalez Noguez A.G.
        • Osorio Solis C.
        • Vacio Olguin A.J.
        Tonsil cancer treated with radiotherapy during a pregnancy: a case report.
        J Radiother Pract. 2020; 19: 197-201
        • Ngu S.L.C.
        • Duval P.
        • Collins C.
        Foetal radiation dose in radiotherapy for breast cancer.
        Australas Radiol. 1992; 36: 321-322https://doi.org/10.1111/j.1440-1673.1992.tb03209.x
        • Antypas C.
        • Sandilos P.
        • Kouvaris J.
        • Balafouta E.
        • Karinou E.
        • Kollaros N.
        • et al.
        Fetal dose evaluation during breast cancer radiotherapy.
        Int J Radiat Oncol Biol Phys. 1998; 40: 995-999
        • Fenig E.
        • Mishaeli M.
        • Kalish Y.
        • Lishner M.
        Pregnancy and radiation.
        Cancer Treat Rev. 2001; 27: 1-7https://doi.org/10.1053/ctrv.2000.0193
        • Van der Giessen P.-H.
        Measurement of the peripheral dose for the tangential breast treatment technique with Co-60 gamma radiation and high energy X-rays.
        Radiother Oncol. 1997; 42: 257-264https://doi.org/10.1016/S0167-8140(96)01884-1
        • Amant F.
        • Loibl S.
        • Neven P.
        • Van Calsteren K.
        Breast cancer in pregnancy.
        Lancet. 2012; 379: 570-579https://doi.org/10.1016/S0140-6736(11)61092-1
        • Azim H.A.
        • Santoro L.
        • Pavlidis N.
        • Gelber S.
        • Kroman N.
        • Azim H.
        • et al.
        Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies.
        Eur J Cancer. 2011; 47: 74-83
        • Woo S.Y.
        • Fuller L.M.
        • Cundiff J.H.
        • Bondy M.L.
        • Hagemeister F.B.
        • McLaughlin P.
        • et al.
        Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin’s disease.
        Int J Radiat Oncol Biol Phys. 1992; 23: 407-412https://doi.org/10.1016/0360-3016(92)90761-6
        • Peccatori F.A.
        • Azim H.A.
        • Pruneri G.
        • Piperno G.
        • Raviele P.R.
        • Preda L.
        • et al.
        Management of anaplastic large-cell lymphoma during pregnancy.
        J Clin Oncol. 2009; 27: e75https://doi.org/10.1200/JCO.2009.22.2042
        • Mazonakis M.
        • Lyraraki E.
        • Varveris C.
        • Samara E.
        • Zourari K.
        • Damilakis J.
        Conceptus dose from involved-field radiotherapy for Hodgkin’s lymphoma on a linear accelerator equipped with MLCsDie Strahlendosis im Fetus von Involved-Field-Radiotherapie wegen Hodgkin-Lymphom an einem Linearbeschleuniger mit Multileafkollimatoren (MLC).
        Strahlenther Onkol. 2009; 185: 355-363
        • Eibye S.
        • Kjær S.K.
        • Mellemkjær L.
        Incidence of pregnancy-associated cancer in Denmark, 1977–2006.
        Obstet Gynecol. 2013; 122: 608-617
        • Mazzola R.
        • Corradini S.
        • Eidemüeller M.
        • Figlia V.
        • Fiorentino A.
        • Giaj-Levra N.
        • et al.
        Modern radiotherapy in cancer treatment during pregnancy.
        Crit Rev Oncol Hematol. 2019; 136: 13-19
        • Gustafsson D.C.
        • Kottmeier H.L.
        Carcinoma of the cervix associated with pregnancy. A study of the radiumhemmet’s series of invasive carcinoma during the period 1932–1956.
        Obstet Gynecol Surv. 1963; https://doi.org/10.1097/00006254-196304000-00038
        • Prem K.A.
        • Makowski E.L.
        • McKelvey J.L.
        Carcinoma of the cervix associated with pregnancy.
        Am J Obstet Gynecol. 1966; 95: 99-108https://doi.org/10.1016/0002-9378(66)90634-X
        • Hopkins M.P.
        • Lavin J.P.
        Cervical cancer in pregnancy.
        Gynecol Oncol. 1996; 63: 293https://doi.org/10.1006/gyno.1996.0324
        • Hunter M.I.
        • Tewari K.
        • Monk B.J.
        Cervical neoplasia in pregnancy. Part 2: current treatment of invasive disease.
        Am J Obstet Gynecol. 2008; 199: 10-18
        • Lonski P.
        • Taylor M.L.
        • Franich R.D.
        • Harty P.
        • Kron T.
        Assessment of leakage doses around the treatment heads of different linear accelerators.
        Radiat Prot Dosim. 2012; 152: 304-312
        • Fraass B.A.
        • van de Geijn J.
        Peripheral dose from megavolt beams.
        Med Phys. 1983; 10: 809-818
        • Kase K.R.
        • Svensson G.K.
        • Wolbarst A.B.
        • Marks M.A.
        Measurements of dose from secondary radiation outside a treatment field.
        Int J Radiat Oncol Biol Phys. 1983; 9: 1177-1183
        • Kourinou K.M.
        • Mazonakis M.
        • Lyraraki E.
        • Damilakis J.
        Photon-beam radiotherapy in pregnant patients: can the fetal dose be limited to 10 cGy or less?.
        Phys Med. 2015; 31: 85-91
        • McParland B.J.
        Peripheral doses of two linear accelerators employing universal wedges.
        Br J Radiol. 1990; 63: 295-298
        • Sherazi S.
        • Kase K.R.
        Measurements of dose from secondary radiation outside a treatment field: Effects of wedges and blocks.
        Int J Radiat Oncol Biol Phys. 1985; 11: 2171-2176
        • Gopalakrishnan Z.
        • Nair R.K.
        • Raghukumar P.
        • Sarin B.
        Dosimetric comparison of treatment plans using physical wedge and enhanced dynamic wedge for the planning of breast radiotherapy.
        J Med Phys. 2018; 43: 46-51
        • Zanini A.
        • Durisi E.
        • Fasolo F.
        • Visca L.
        • Ongaro C.
        • Nastasi U.
        • et al.
        Neutron spectra in a tissue equivalent phantom during photon radiotherapy treatment by LINACS.
        Radiat Prot Dosim. 2004; 110: 157-160
        • Howell R.M.
        • Kry S.F.
        • Burgett E.
        • Followill D.
        • Hertel N.E.
        Effects of tertiary MLC configuration on secondary neutron spectra from 18 MV x-ray beams for the Varian 21EX linear accelerator.
        Med Phys. 2009; 36: 4039-4046
        • Howell R.M.
        • Kry S.F.
        • Burgett E.
        • Hertel N.E.
        • Followill D.S.
        Secondary neutron spectra from modern Varian, Siemens, and Elekta linacs with multileaf collimators.
        Med Phys. 2009; 36: 4027-4038
        • Kry S.F.
        • Salehpour M.
        • Followill D.S.
        • Stovall M.
        • Kuban D.A.
        • White R.A.
        • et al.
        Out-of-field photon and neutron dose equivalents from step-and-shoot intensity-modulated radiation therapy.
        Int J Radiat Oncol Biol Phys. 2005; 62: 1204-1216
        • Al-Ghamdi H.
        • Fazal-ur-Rehman
        • Al-Jarallah M.I.
        • Maalej N.
        Photoneutron intensity variation with field size around radiotherapy linear accelerator 18-MeV X-ray beam.
        Radiat Meas. 2008; 43: S495-S499
      9. Neutron contamination from medical electron accelerators: recommendations of the National Council on Radiation Protection and Measurements. (The Council, 1984).

        • Expósito M.R.
        • Sánchez-Nieto B.
        • Terrón J.A.
        • Domingo C.
        • Gómez F.
        • Sánchez-Doblado F.
        Neutron contamination in radiotherapy: estimation of second cancers based on measurements in 1377 patients.
        Radiother Oncol. 2013; 107: 234-241
        • Naseri A.
        • Mesbahi A.
        A review on photoneutrons characteristics in radiation therapy with high-energy photon beams.
        Rep Pract Oncol Radiother. 2010; 15: 138-144
        • Followill D.S.
        • Stovall M.S.
        • Kry S.F.
        • Ibbott G.S.
        Neutron source strength measurements for Varian, Siemens, Elekta, and General Electric linear accelerators.
        J Appl Clin Med Phys. 2003; 4: 189-194
        • Schneider U.
        • Agosteo S.
        • Pedroni E.
        • Besserer J.
        Secondary neutron dose during proton therapy using spot scanning.
        Int J Radiat Oncol Biol Phys. 2002; 53: 244-251
        • Blattmann H.
        Beam delivery systems for charged particles.
        Radiat Environ Biophys. 1992; 31: 219-231
        • Binns P.J.
        • Hough J.H.
        Secondary dose exposures during 200 MeV proton therapy.
        Radiat Prot Dosim. 1997; 70: 441-444
        • Ware D.E.
        • Huda W.
        • Mergo P.J.
        • Litwiller A.L.
        Radiation effective doses to patients undergoing abdominal CT examinations.
        Radiology. 1999; 210: 645-650
        • Roy S.C.
        • Sandison G.A.
        Scattered neutron dose equivalent to a fetus from proton therapy of the mother.
        Radiat Phys Chem. 2004; 71: 997-998
        • Dawson L.A.
        • Jaffray D.A.
        Advances in image-guided radiation therapy.
        J Clin Oncol. 2007; 25: 938-946
        • Perks J.R.
        • Lehmann J.
        • Chen A.M.
        • Yang C.C.
        • Stern R.L.
        • Purdy J.A.
        Comparison of peripheral dose from image-guided radiation therapy (IGRT) using kV cone beam CT to intensity-modulated radiation therapy (IMRT).
        Radiother Oncol. 2008; 89: 304-310
        • Ding G.X.
        • Duggan D.M.
        • Coffey C.W.
        Accurate patient dosimetry of kilovoltage cone-beam CT in radiation therapy.
        Med Phys. 2008; 35: 1135-1144
        • Kan M.W.K.
        • Leung L.H.T.
        • Wong W.
        • Lam N.
        Radiation dose from cone beam computed tomography for image-guided radiation therapy.
        Int J Radiat Oncol Biol Phys. 2008; 70: 272-279
        • Peet S.C.
        • Kairn T.
        • Lancaster C.M.
        • Trapp J.V.
        • Sylvander S.R.
        • Crowe S.B.
        Measuring foetal dose from tomotherapy treatments.
        Med Dosim. 2021; 46: 342-346
        • Dusi F.
        • Guida F.
        • Garcia E.N.V.
        • Rossato M.A.
        • Germani A.
        • Sapignoli S.
        • et al.
        Fetal dose estimation for Virtual Tangential-fields Arc Therapy whole breast irradiation by optically stimulated luminescence dosimeters.
        Physica Medica: Eur J Med Phys. 2022; 101: 44-49
        • Bradley B.
        • Fleck A.
        • Osei E.K.
        Normalized data for the estimation of fetal radiation dose from radiotherapy of the breast.
        BJR. 2006; 79: 818-827
        • Stovall M.
        • Weathers R.
        • Kasper C.
        • Smith S.A.
        • Travis L.
        • Ron E.
        • et al.
        Dose reconstruction for therapeutic and diagnostic radiation exposures: use in epidemiological studies.
        Radiat Res. 2006; 166: 141-157
      10. Stratakis J, Papadakis A. Radiation Dose Management of Pregnant Patients, Pregnant Staff and Paediatric Patients. (IOP, 2019).

        • Xu X.G.
        An exponential growth of computational phantom research in radiation protection, imaging, and radiotherapy: a review of the fifty-year history.
        Phys Med Biol. 2014; 59: R233-R302
        • Zaidi H.
        • Tsui B.M.W.
        Review of computational anthropomorphic anatomical and physiological models.
        Proc IEEE. 2009; 97: 1938-1953
        • Makkia R.
        • Nelson K.
        • Zaidi H.
        • Dingfelder M.
        Construction of realistic hybrid computational fetal phantoms from radiological images in three gestational ages for radiation dosimetry applications.
        Phys Med Biol. 2019; 64205003
        • Paulbeck C.
        • Griffin K.
        • Lee C.
        • Cullings H.
        • Egbert S.D.
        • Funamoto S.
        • et al.
        Dosimetric impact of a new computational voxel phantom series for the japanese atomic bomb survivors: pregnant females.
        Radiat Res. 2019; 192: 538
        • Suwanbut P.
        • Liamsuwan T.
        • Nantajit D.
        • Masa-Nga W.
        • Tannanonta C.
        Assessment of fetal dose and health effect to the fetus from breast cancer radiotherapy during pregnancy.
        Life. 2022; 12: 1-9
        • Cabral M.O.M.
        • Vieira J.W.
        • Leal Neto V.
        • de Andrade Lima F.R.
        Development of a pregnant woman phantom using polygonal mesh, for dosimetric evaluations.
        Braz J Rad Sci. 2015; 3
        • Catusso L.
        • Santos W.S.
        • da Silva R.M.V.
        • Valença J.V.B.
        Mobile shielding evaluation on the fetal dose during a breast radiotherapy using Monte Carlo simulation.
        Phys Med. 2021; 84: 24-32
        • Yeom Y.S.
        • Griffin K.T.
        • Mille M.M.
        • Lee C.
        • O’Reilly S.
        • Dong L.
        • et al.
        Fetal dose from proton pencil beam scanning craniospinal irradiation during pregnancy: a Monte Carlo study.
        Phys Med Biol. 2022; 67035003
        • Shine N.S.
        • Paramu R.
        • Gopinath M.
        • Jaon Bos R.C.
        • Jayadevan P.M.
        Out-of-field dose calculation by a commercial treatment planning system and comparison by Monte Carlo simulation for Varian TrueBeam®.
        J Med Phys. 2019; 44: 156
        • Howell R.M.
        • Scarboro S.B.
        • Kry S.F.
        • Yaldo D.Z.
        Accuracy of out-of-field dose calculations by a commercial treatment planning system.
        Phys Med Biol. 2010; 55: 6999-7008
        • Huang J.Y.
        • Followill D.S.
        • Wang X.A.
        • Kry S.F.
        Accuracy and sources of error of out-of field dose calculations by a commercial treatment planning system for intensity-modulated radiation therapy treatments.
        J Appl Clin Med Phys. 2013; 14: 186-197
        • Ogretici A.
        • Çakir A.
        • Akbaş U.
        • Köksal C.
        • Kalafat Ü.
        • Tambaş M.
        • et al.
        A phantom study on fetal dose reducing factors in pregnant patients with breast cancer during radiotherapy treatment.
        J Med Phys. 2017; 42: 128-132
        • Sharma S.C.
        • Williamson J.F.
        • Khan F.M.
        • Lee C.K.K.
        Measurement and calculation of ovary and fetus dose in extended field radiotherapy for 10 MV X rays.
        Int J Radiat Oncol Biol Phys. 1981; 7: 843-846
        • 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
        • Forster R.A.
        • Godfrey T.N.K.
        Lecture Notes in PhysicsMonte-Carlo Methods and Applications in Neutronics, Photonics and Statistical Physics. Springer-Verlag, Berlin/Heidelberg1985: 33-55
        • Mazonakis M.
        • Tzedakis A.
        • Damilakis J.
        Monte Carlo simulation of radiotherapy for breast cancer in pregnant patients: how to reduce the radiation dose and risks to fetus?.
        Radiat Prot Dosim. 2017; 175: 10-16
        • Bednarz B.
        • Xu X.G.
        A feasibility study to calculate unshielded fetal doses to pregnant patients in 6-MV photon treatments using Monte Carlo methods and anatomically realistic phantoms.
        Med Phys. 2008; 35: 3054-3061
        • De Saint-Hubert M.
        • Tymińska K.
        • Stolarczyk L.
        • Brkić H.
        Fetus dose calculation during proton therapy of pregnant phantoms using MCNPX and MCNP6.2 codes.
        Radiat Meas. 2021; 149: 106665
        • Perl J.
        • Shin J.
        • Schümann J.
        • Faddegon B.
        • Paganetti H.
        TOPAS: An innovative proton Monte Carlo platform for research and clinical applications.
        Med Phys. 2012; 39: 6818-6837
        • Geng C.
        • Moteabbed M.
        • Seco J.
        • Gao Y.
        • George Xu X.
        • Ramos-Méndez J.
        • et al.
        Dose assessment for the fetus considering scattered and secondary radiation from photon and proton therapy when treating a brain tumor of the mother.
        Phys Med Biol. 2016; 61: 683-695
        • Islam M.K.
        • Purdie T.G.
        • Norrlinger B.D.
        • Alasti H.
        • Moseley D.J.
        • Sharpe M.B.
        • et al.
        Patient dose from kilovoltage cone beam computed tomography imaging in radiation therapy: patient dose from kilovoltage cone beam CT.
        Med Phys. 2006; 33: 1573-1582
        • Hioki K.
        • Araki F.
        • Ohno T.
        • Nakaguchi Y.
        • Tomiyama Y.
        Absorbed dose measurements for kV-cone beam computed tomography in image-guided radiation therapy.
        Phys Med Biol. 2014; 59: 7297-7313
        • Lehmann J.
        • Stern R.L.
        • Levy J.
        • Daly T.P.
        • Hartmann Siantar C.L.
        • Goldberg Z.
        Radiation phantom with humanoid shape and adjustable thickness (RPHAT).
        Phys Med Biol. 2004; 49: N125-N129
        • Mege J.-P.
        • Wenzhao S.
        • Veres A.
        • Auzac G.
        • Diallo I.
        • Lefkopoulos D.
        Evaluation of MVCT imaging dose levels during helical IGRT: comparison between ion chamber, TLD, and EBT3 films.
        J Appl Clin Med Phys. 2016; 17: 143-157
        • Ding G.X.
        • Coffey C.W.
        Radiation dose from kilovoltage cone beam computed tomography in an image-guided radiotherapy procedure.
        Int J Radiat Oncol Biol Phys. 2009; 73: 610-617
        • Mazonakis M.
        • Tzedakis A.
        • Varveris C.
        • Damilakis J.
        Radiotherapy for supradiaphragmatic Hodgkin’s disease: determination of the proper fetal shielding conditions using Monte Carlo methodology.
        Phys Med. 2011; 27: 181-187
        • Moeckli R.
        • Ozsahin M.
        • Pache G.
        • Valley J.-F.
        • Mirimanoff R.-O.
        • Azria D.
        Fetal dose reduction in head and neck radiotherapy of a pregnant woman.
        Z Med Phys. 2004; 14: 168-172
        • Orlandi E.
        • Zonca G.
        • Pignoli E.
        • Stucchi C.
        • Borroni M.
        • Collini P.
        • et al.
        Postoperative radiotherapy for synovial sarcoma of the head and neck during pregnancy: clinical and technical management and fetal dose estimates.
        Tumori. 2007; 93: 45-52
        • Josipović M.
        • Nyström H.
        • Kjær-Kristoffersen F.
        IMRT in a pregnant patient: how to reduce the fetal dose?.
        Med Dosim. 2009; 34: 301-310
        • Han B.
        • Bednarz B.
        • Xu X.G.
        A study of the shielding used to reduce leakage and scattered radiation to the fetus in a pregnant patient treated with a 6-MV external x-ray beam.
        Health Phys. 2009; 97: 581-589
        • Da Costa E.C.
        • Da Rosa L.A.R.
        • Batista D.V.S.
        Fetus absorbed dose evaluation in head and neck radiotherapy procedures of pregnant patients.
        Appl Radiat Isot. 2015; 100: 11-15
        • Atarod M.
        • Shokrani P.
        • Pourmoghadas A.
        Design of a generally applicable abdominal shield for reducing fetal dose during radiotherapy of common malignancies in pregnant patients.
        Iran J Radiat Res. 2012; 10: 151-156
        • Horowitz D.P.
        • Wang T.J.C.
        • Wuu C.-S.
        • Feng W.
        • Drassinower D.
        • Lasala A.
        • et al.
        Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy.
        J Neurooncol. 2014; 120: 405-409
        • Kang S.
        • Kim K.H.
        • Kang S.W.
        • Shin D.S.
        • Lee S.
        • Chung J.B.
        Evaluation of a new foetal shielding device for pregnant brain tumour patients.
        Radiat Oncol. 2021; 16: 1-10
        • Owrangi A.M.
        • Roberts D.A.
        • Covington E.L.
        • Hayman J.A.
        • Masi K.M.
        • Lee C.
        • et al.
        Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield.
        J Appl Clin Med Phys. 2016; 17: 34-46
        • Buchgeister M.
        • Mondry A.
        • Spillner P.
        • Paulsen F.
        • Belka C.
        • Bamberg M.
        A special radiation shielding for the radiotherapy of a pregnant patient.
        Strahlenther Onkol. 2008; 184: 80-85
        • Filipov D.
        • Schelin H.R.
        • Soboll D.S.
        • Denyak V.
        Evaluation of fetal dose in breast radiotherapy with shielding and wedges.
        IEEE Trans Nucl Sci. 2013; 60: 792-796
        • Candela-Juan C.
        • Gimeno-Olmos J.
        • Pujades M.C.
        • Rivard M.J.
        • Carmona V.
        • Lliso F.
        • et al.
        Fetal dose measurements and shielding efficiency assessment in a custom setup of 192Ir brachytherapy for a pregnant woman with breast cancer.
        Phys Med. 2015; 31: 286-292
        • Mazonakis M.
        • Varveris H.
        • Fasoulaki M.
        • Damilakis J.
        Radiotherapy of Hodgkin’s disease in early pregnancy: embryo dose measurements.
        Radiother Oncol. 2003; 66: 333-339
        • Chatterson L.C.
        • Leswick D.A.
        • Fladeland D.A.
        • Hunt M.M.
        • Webster S.T.
        Lead versus Bismuth-antimony shield for fetal dose reduction at different gestational ages at CT pulmonary angiography.
        Radiology. 2011; 260: 560-567
        • Moore W.
        • Bonvento M.J.
        • Lee D.
        • Dunkin J.
        • Bhattacharji P.
        Reduction of fetal dose in computed tomography using anterior shields.
        J Comput Assist Tomogr. 2015; 39: 298-300
        • Ghaznavi H.
        Reducing fetal radiation dose in computed tomography for pregnant patients: a literature review.
        Gazette Med Sci. 2021; 2: 35-43
        • Roy S.C.
        • Sandison G.A.
        Shielding for neutron scattered dose to the fetus in patients treated with 18 MV x-ray beams.
        Med Phys. 2000; 27: 1800-1803