- Email: [email protected]
The impact of early life exposure to diagnostic and therapeutic radiation on childhood cancer risk
Physica Medica (2013) 29, 221e223
Available online at www.sciencedirect.com
journal homepage: http://intl.elsevierhealth.com/journals/ejmp
LETTER TO THE EDITOR
The impact of early life exposure to diagnostic and therapeutic radiation on childhood cancer risk As is commonly known, radiological protection of paediatric and pregnant patients exposed to medical diagnostic and therapeutic radiation has always received special attention. This is because children, embryos and foetuses have higher radiation sensitivities, and they exhibit an increased likelihood of developing radiation-induced cancer over their lives compared with people who are exposed to radiation as adults [1,2]. Considering the potential risk of stochastic effects (i.e., incurring cancer or heritable effects) in children, the IAEA (International Atomic Energy Agency) and the ICRP (International Commission on Radiological Protection) have paid particular attention to medical radiation exposure in children.
Diagnostic exposure Among the most recent studies investigating the association between early life exposure to diagnostic radiation and the risk of childhood cancer, Rajaraman et al. published an excellent study that indicates possible risks of cancer from radiation at doses lower than those associated with common procedures such as computed tomography scans. The findings suggest that diagnostic radiation for imaging procedures involving the abdomen and pelvis of mothers during pregnancy and in very young children should be used cautiously [3]. That study provided valuable data for the estimation of the risk of radiation carcinogenesis in childhood. However, we believe that detailed data on the dosage levels of all of the included populations are essential when analysing the relationship between radiation exposure and cancer risk. Based on the ICRP recommendations, the radiation dose is mentioned and is necessary for assessing the risk of cancer [4]. Thus, the conclusions seem to be inconsistent with the significance of the results, and the paper is far from conclusive. The term “diagnostic reference level” (DRL) is now used in the context of the optimisation of protection of patients exposed to medical radiation. The DRL is used to limit the patient’s dosage to a level that is commensurate with the medical purpose [4,5]. DRL is also called “reference dose level” in paediatric patients and may decrease the individual dose of a given patient, is expected to
reduce the risk of stochastic radiation effects and may have significant practical value in medical diagnostic imaging procedures. However, the management of radioprotection in paediatric radiology has not received sufficient attention in China; investigations of diagnostic radiation dosages, estimations of risk, guidelines for the reasonable application of diagnostic radiation to children and the optimisation of radioprotection in medical exposure are all seem to be lacking. In China, there is a strong need to justify and optimise diagnostic radiation examinations in children and to formulate and disseminate the “reference dose levels”.
Therapeutic exposure: in utero exposure For cancer risks associated with radiotherapy, radiation doses to distal organs are a concern, especially for pregnant patients, because radiotherapy is complicated by the sensitivity of the foetus to in utero exposure [6]. The use of supplemental shielding can substantially reduce foetal exposure. The dose to the foetus resulting from most conventional radiography is less than 0.01 Gy. However, the radiation dose depends heavily on the type of treatment used. The risk of radiation-induced stochastic effects for childhood cancer and leukaemia is somewhat higher than the spontaneous incidence of 2e3 per 1000, with a relative risk of 1.4 at 0.01 Gy, but most likely lower [7]. The largest caseecontrol study of cancer after in utero irradiation found that radiation increased the incidences of all types of childhood cancer by approximately the same degree [1]. Data from atomic bomb survivors suggest that the lifetime cancer risk from in utero exposure may be similar to that from exposure in early childhood [1,4,5].
Therapeutic exposure: second cancers in paediatric patients The Childhood Cancer Survivor Study (CCSS) demonstrated that long-term survivors of childhood cancer who received radiotherapy were at a significantly increased risk for the development of second malignant neoplasms (SMNs): the incidence of SMNs is approximately 10e20% 30 years after treatment [8]. The estimation of the risk of developing SMNs is a very complicated procedure, as many factors may confound the results.
1120-1797/$ - see front matter ª 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejmp.2012.02.002
222 In a Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma and radiotherapy were associated with increased risk of subsequent neoplasms [8]. Similarly, the atomic bomb survivor database also showed that the risk of developing SMNs depends on the age at exposure and decreases from approximately 15% per unit dose equivalent (Sv 1) at under 10 years of age to approximately 1% Sv 1 for adults exposed at over 60 years age [9]. Additionally, genetic susceptibility, lifestyle choices and environmental factors also raise questions regarding whether paediatric patients are more sensitive and susceptible to radiation-induced cancer [10].
Conclusions and suggestions 1 The IAEA established networks of medical professionals for “radiation protection of children” in Europe and Asia in 2010 [10]. The management of the radioprotection of children dose not receive much attention in China. The Chinese health authority should consider participating in the network because China is not currently one of the member states. As the largest developing country, we are responsible for promoting initiatives for the radiation protection of children and for acting in accordance with the mission, actions and mechanisms [10] of the network in medical practice. 2 Recommendations state that radiotherapy should not be administered to pregnant patients until after delivery because of the risks associated with foetal exposure to radiation; however, such advice is not tenable [7]. These patients will benefit from optimised suggestions from a professional multidisciplinary team, which should include a gynaecologist, a foetal medicine specialist, a radiation oncologist, a paediatric oncologist and a reproductive endocrinologist. Only through a multidisciplinary approach will patients make adequate decisions and receive optimal care for their cancers. 3 The risk of developing SMNs constitutes a challenge for treating paediatric radiotherapy patients. There are several suggestions from available research for reducing the risk of developing SMNs from radiotherapy. Modifying treatment units to reduce stray radiation is an obvious and attractive approach. Having regular medical followup or practicing recommended cancer screening for the patients are good SMN prevention strategies following childhood cancer radiotherapy. New research studies are needed to strengthen the initial evidence used to design personalised treatment strategies [8,9].
Conflict of interest There are no actual or potential conflicts of interest. All authors have reviewed the manuscript and have verified the contents. Permission has been obtained from the head of the First People’s Hospital of Nantong for publication.
Acknowledgements Our work was supported by the National Natural Science Foundation of China (No. 31170804 and 10705016), the
Letter to the Editor Special Project from the Ministry of Health in China (201002009), the Natural Science Foundation of Tianjin (Nos. 10JCZDJC16900, 11ZCGYSY02400), the Doctoral Science Research Foundation for High School of the National Education Ministry (No. 20101106110046) and the Development Foundation of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College (SF1101, SF1102).
References [1] Streffer C, Shore R, Konermann G, Meadows A, Uma Devi P, Preston Withers J, et al. Biological effects after prenatal irradiation (embryo and fetus). A report of the International Commission on Radiological Protection. Ann ICRP 2003; 33(1e2):5e206. [2] Muhogora WE, Ahmed NA, Alsuwaidi JS, Beganovic A, CirajBjelac O, Gershan V, et al. Paediatric CT examinations in 19 developing countries: frequency and radiation dose. Radiat Prot Dosim 2010;140(1):49e58. [3] Rajaraman P, Simpson J, Neta G, Berrington de Gonzalez A, Ansell P, Linet MS, et al. Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study. BMJ 2011;342:d472. [4] ICRP. Recommendations of the International Commission on Radiological Protection. Ann ICRP 2007;37(2e4) [ICRP Publication 103]. [5] Wrixon AD. New ICRP recommendations. J Radiol Prot 2008; 28:161e8. [6] Mu ¨nter MW, Wengenroth M, Fehrenbacher G, Schardt D, Nikoghosyan A, Durante M, et al. Heavy ion radiotherapy during pregnancy. Fertil Steril 2010;94(6):2329.e5e7. [7] Kal HB, Struikmans H. Radiotherapy during pregnancy: fact and fiction. Lancet Oncol 2005;6:328. [8] Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2010;102(14):1083e95. [9] Newhauser WD, Durante M. Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer 2011;11(6):438e48. [10] https://rpop.iaea.org/RPOP/RPoP/Content/SpecialGroups/ 2_Children/children-network.htm.
Yong Jian Ju Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China Li Qing Du Jia Cao Yan Wang Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China Xu Dong Miao Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China
Letter to the Editor Hong Wang Feng Hua Chen Fei Yue Fan Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China Gao Ren Wang* Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China
223 Qiang Liu** Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China *Corresponding author. E-mail address: [email protected] **Corresponding author. E-mail address: [email protected]
19 September 2011
Available online at www.sciencedirect.com
journal homepage: http://intl.elsevierhealth.com/journals/ejmp
LETTER TO THE EDITOR
The impact of early life exposure to diagnostic and therapeutic radiation on childhood cancer risk As is commonly known, radiological protection of paediatric and pregnant patients exposed to medical diagnostic and therapeutic radiation has always received special attention. This is because children, embryos and foetuses have higher radiation sensitivities, and they exhibit an increased likelihood of developing radiation-induced cancer over their lives compared with people who are exposed to radiation as adults [1,2]. Considering the potential risk of stochastic effects (i.e., incurring cancer or heritable effects) in children, the IAEA (International Atomic Energy Agency) and the ICRP (International Commission on Radiological Protection) have paid particular attention to medical radiation exposure in children.
Diagnostic exposure Among the most recent studies investigating the association between early life exposure to diagnostic radiation and the risk of childhood cancer, Rajaraman et al. published an excellent study that indicates possible risks of cancer from radiation at doses lower than those associated with common procedures such as computed tomography scans. The findings suggest that diagnostic radiation for imaging procedures involving the abdomen and pelvis of mothers during pregnancy and in very young children should be used cautiously [3]. That study provided valuable data for the estimation of the risk of radiation carcinogenesis in childhood. However, we believe that detailed data on the dosage levels of all of the included populations are essential when analysing the relationship between radiation exposure and cancer risk. Based on the ICRP recommendations, the radiation dose is mentioned and is necessary for assessing the risk of cancer [4]. Thus, the conclusions seem to be inconsistent with the significance of the results, and the paper is far from conclusive. The term “diagnostic reference level” (DRL) is now used in the context of the optimisation of protection of patients exposed to medical radiation. The DRL is used to limit the patient’s dosage to a level that is commensurate with the medical purpose [4,5]. DRL is also called “reference dose level” in paediatric patients and may decrease the individual dose of a given patient, is expected to
reduce the risk of stochastic radiation effects and may have significant practical value in medical diagnostic imaging procedures. However, the management of radioprotection in paediatric radiology has not received sufficient attention in China; investigations of diagnostic radiation dosages, estimations of risk, guidelines for the reasonable application of diagnostic radiation to children and the optimisation of radioprotection in medical exposure are all seem to be lacking. In China, there is a strong need to justify and optimise diagnostic radiation examinations in children and to formulate and disseminate the “reference dose levels”.
Therapeutic exposure: in utero exposure For cancer risks associated with radiotherapy, radiation doses to distal organs are a concern, especially for pregnant patients, because radiotherapy is complicated by the sensitivity of the foetus to in utero exposure [6]. The use of supplemental shielding can substantially reduce foetal exposure. The dose to the foetus resulting from most conventional radiography is less than 0.01 Gy. However, the radiation dose depends heavily on the type of treatment used. The risk of radiation-induced stochastic effects for childhood cancer and leukaemia is somewhat higher than the spontaneous incidence of 2e3 per 1000, with a relative risk of 1.4 at 0.01 Gy, but most likely lower [7]. The largest caseecontrol study of cancer after in utero irradiation found that radiation increased the incidences of all types of childhood cancer by approximately the same degree [1]. Data from atomic bomb survivors suggest that the lifetime cancer risk from in utero exposure may be similar to that from exposure in early childhood [1,4,5].
Therapeutic exposure: second cancers in paediatric patients The Childhood Cancer Survivor Study (CCSS) demonstrated that long-term survivors of childhood cancer who received radiotherapy were at a significantly increased risk for the development of second malignant neoplasms (SMNs): the incidence of SMNs is approximately 10e20% 30 years after treatment [8]. The estimation of the risk of developing SMNs is a very complicated procedure, as many factors may confound the results.
1120-1797/$ - see front matter ª 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejmp.2012.02.002
222 In a Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma and radiotherapy were associated with increased risk of subsequent neoplasms [8]. Similarly, the atomic bomb survivor database also showed that the risk of developing SMNs depends on the age at exposure and decreases from approximately 15% per unit dose equivalent (Sv 1) at under 10 years of age to approximately 1% Sv 1 for adults exposed at over 60 years age [9]. Additionally, genetic susceptibility, lifestyle choices and environmental factors also raise questions regarding whether paediatric patients are more sensitive and susceptible to radiation-induced cancer [10].
Conclusions and suggestions 1 The IAEA established networks of medical professionals for “radiation protection of children” in Europe and Asia in 2010 [10]. The management of the radioprotection of children dose not receive much attention in China. The Chinese health authority should consider participating in the network because China is not currently one of the member states. As the largest developing country, we are responsible for promoting initiatives for the radiation protection of children and for acting in accordance with the mission, actions and mechanisms [10] of the network in medical practice. 2 Recommendations state that radiotherapy should not be administered to pregnant patients until after delivery because of the risks associated with foetal exposure to radiation; however, such advice is not tenable [7]. These patients will benefit from optimised suggestions from a professional multidisciplinary team, which should include a gynaecologist, a foetal medicine specialist, a radiation oncologist, a paediatric oncologist and a reproductive endocrinologist. Only through a multidisciplinary approach will patients make adequate decisions and receive optimal care for their cancers. 3 The risk of developing SMNs constitutes a challenge for treating paediatric radiotherapy patients. There are several suggestions from available research for reducing the risk of developing SMNs from radiotherapy. Modifying treatment units to reduce stray radiation is an obvious and attractive approach. Having regular medical followup or practicing recommended cancer screening for the patients are good SMN prevention strategies following childhood cancer radiotherapy. New research studies are needed to strengthen the initial evidence used to design personalised treatment strategies [8,9].
Conflict of interest There are no actual or potential conflicts of interest. All authors have reviewed the manuscript and have verified the contents. Permission has been obtained from the head of the First People’s Hospital of Nantong for publication.
Acknowledgements Our work was supported by the National Natural Science Foundation of China (No. 31170804 and 10705016), the
Letter to the Editor Special Project from the Ministry of Health in China (201002009), the Natural Science Foundation of Tianjin (Nos. 10JCZDJC16900, 11ZCGYSY02400), the Doctoral Science Research Foundation for High School of the National Education Ministry (No. 20101106110046) and the Development Foundation of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College (SF1101, SF1102).
References [1] Streffer C, Shore R, Konermann G, Meadows A, Uma Devi P, Preston Withers J, et al. Biological effects after prenatal irradiation (embryo and fetus). A report of the International Commission on Radiological Protection. Ann ICRP 2003; 33(1e2):5e206. [2] Muhogora WE, Ahmed NA, Alsuwaidi JS, Beganovic A, CirajBjelac O, Gershan V, et al. Paediatric CT examinations in 19 developing countries: frequency and radiation dose. Radiat Prot Dosim 2010;140(1):49e58. [3] Rajaraman P, Simpson J, Neta G, Berrington de Gonzalez A, Ansell P, Linet MS, et al. Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study. BMJ 2011;342:d472. [4] ICRP. Recommendations of the International Commission on Radiological Protection. Ann ICRP 2007;37(2e4) [ICRP Publication 103]. [5] Wrixon AD. New ICRP recommendations. J Radiol Prot 2008; 28:161e8. [6] Mu ¨nter MW, Wengenroth M, Fehrenbacher G, Schardt D, Nikoghosyan A, Durante M, et al. Heavy ion radiotherapy during pregnancy. Fertil Steril 2010;94(6):2329.e5e7. [7] Kal HB, Struikmans H. Radiotherapy during pregnancy: fact and fiction. Lancet Oncol 2005;6:328. [8] Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2010;102(14):1083e95. [9] Newhauser WD, Durante M. Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer 2011;11(6):438e48. [10] https://rpop.iaea.org/RPOP/RPoP/Content/SpecialGroups/ 2_Children/children-network.htm.
Yong Jian Ju Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China Li Qing Du Jia Cao Yan Wang Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China Xu Dong Miao Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China
Letter to the Editor Hong Wang Feng Hua Chen Fei Yue Fan Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China Gao Ren Wang* Department of Radiation Therapy, The First People’s Hospital of Nantong, No. 6 North Haierxiang Road, 226001 Nantong, Jiangsu Province, People’s Republic of China
223 Qiang Liu** Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, 238, Baidi Road, 300192 Tianjin, People’s Republic of China *Corresponding author. E-mail address: [email protected] **Corresponding author. E-mail address: [email protected]
19 September 2011