Early in Life. Noboru Takamura, M.D., Ph.D.

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1 Health Risks of Radiation Exposure Early in Life Noboru Takamura, M.D., Ph.D.

2 Diagnostic Radiologic Procedures In recent years, the largest source of general population exposure to radiation has shifted fromenvironmental radiation to medical diagnostic and therapeutic radiological procedures. There is tremendous variation in estimated doses from different diagnostic radiologic i procedures. Estimated tddoses are 15 fold higher for screening mammograms, 70 fold higher from barium swallow examinations, and 750 fold higher from chest CT than doses from a single chest radiograph.

3 Typical Effective Doses from Different Diagnostic Examinations Type of examination Effective dose (msv) Radiography Skull (1) Chest (1) Abdomen 0.46 (35) Spine (20 30) Dental (1) Mammography y( (4 views) Screening 0.2 (15) Diagnostic fluoroscopy procedures Barium 1 5 (70 350) Angiography 2 7 ( ) Type of examination Effective dose (msv) Computed tomography Head 2 (150) Chest 10 (750) Pelvis 10 (750) Spine 5 8 ( ) Diagnostic nuclear medicine Bone ( 99m Tc) 3 (200) Heart ( 201 Tl) 13 (950) Lung ( 99m Tc) 0.9 (70) Thyroid ( 99m T)09(70) Tc) 0.9 PET ( 18 F FDG) 7 (500)

4 Estimated Doses for in Utero and Early Childhood Radiation from Diagnostic Medical Radiologic Procedures

5 Radiation Dose for Medical Diagnostic Procedures in Children Even though cancer risks associated with a given radiation dose are known to be higher for exposures during childhood and adolescence than for exposures during adulthood, and have been thought to be greater for prenatal than postnatal exposures, published radiation dose estimates for medical diagnostic procedures in children and data based on nationwide surveys are still limited.

6 Radiation Dose to Embryos/Fetus from Maternal Diagnostic Examination Type of examination Embryo/fetus dose (mgy) Radiography Chest AP or PA <0.01 Abdomen 2.9 Special diagnostic procedures Barium enema 6.1 Intravenous pyelogram 4.8 Diagnostic nuclearmedicine 99m Tc MDP (bone) Ga citrate 18 Computed tomography Lung 1.2 Liver 3.6 L spine 2.8 Pelvis 89

7 Radiation Dose to Embryos/Fetus from Maternal Diagnostic Examination While the decline in prenatal obstetrical radiologic procedures and replacement of diagnostic procedures involving ionizing radiation with sonography has resulted in notable reduction of an important source of early life exposures to ionizing radiation, pregnant women continue to undergo imaging procedures to evaluate non obstetric obstetric medical conditions. CT examinations, certain fluoroscopic procedures, and a few nuclear medicine procedures were characterized by higher fetal doses than other types of diagnostic examinations. ea ato

8 Radiation Dose to Children by age at Exposure from Diagnostic i Examination i Type of examination Radiation dose of children (by age at exposure) 0 year 1 year 5 years 10 years 15 years Adults Radiography Skull (mgy) Chest (mgy) Abdomen (mgy) Pelvis (mgy) Computed tomography Brain (msv) Facial bone (msv) Chest (msv) Abdomen (msv) Spine (msv)

9 Pediatric Exposure to Diagnostic Medical Radiation In general, the average estimated entrance surface dose for radiographic procedures and the dose area product for fluoroscopic procedures increases with increasing age. While increasing i effective dose with ihage is apparent for some CT procedures (e.g., chest and abdomen), for others (e.g., brain) a different pattern is evident. A major reason for differences in estimated effective doses between pediatric i patients of different ages and between pediatric i and adult patients is body size.

10 Pediatric Exposure to Diagnostic Medical Radiation For a given intensity of X ray beam, younger pediatric patient receive higher radiation doses than older children. This is because the smaller the size of patient, the less the attenuation of the primary X ray beam, and thus the higher the radiation dose. In addition, the organs and tissues of pediatric patients are smaller and thinner and organs are closer together in children, so that scatter from the primary beam can reach adjacent organs and tissues in children more easily than in adults.

11 Patterns in CT Use in Pediatric Patients Use of CT diagnostic i examinations i varies depending on country, facility and time period of examination. The proportion of pediatric patients aged 0 15 years old undergoing CT scans ranged 3 16% depending on country. M t t di tdhi h t f CT Most studies reported higher rates of CT examination for boys than girls, which has been attributed to higher trauma rates among boys.

12 Patterns in CT use in Pediatric Patients The head is the most common anatomic region for CT examinations in children, whereas the trunk is the region most frequently evaluated in adults. For children and adolescents undergoing CT, the most common reasons were ill defined conditions, such as headaches h and dizziness, i and respiratory diseases, whereas in infants, congenital anomalies were the most common reasons.

13 Prenatal Diagnostic Radiation and Pediatric Cancer Risks

14 Risks for All Pediatric Cancers Combined with Exposure to in Utero Diagnostic i Rdi Radiationi Authors, country Cases/Cont. Source of X ray Estimated relative risk information Any Abd. Pelv. Stewart et al. 1,299/1,299 Interview, medical UK records, questionnaire Bithell et al. 8,513/8,513 Interview, medical UK records, questionnaire Knox et al. 14,759/14,759 Interview, medical 1.9 UK records, questionnaire MacMahon 556/7,242 Medical records USA

15 Risks for All Pediatric Cancers Combined with Exposure to in Utero Diagnostic Radiation UK study first reported statistically significant 1.6 fold and 2.1 fold mortality excesses in all pediatric cancers among offspring of mothers who underwent diagnostic radiation examination. After an additional 12 years follow up, they reported 1.5 fold and 2.5 fold significant mortality risks in the same cohort. Similar results were reported from a case control study conducted in U.S. where the investigators observed significant 1.4 fold and 1.6 fold increases in total childhood cancer mortality among offspring of mothers who underwent diagnostic radiation examination.

16 Risks for Childhood Leukemia Combined with Exposure to in Utero Diagnostic Radiation Rditi Authors, country Cases/Cont. Source of X ray Estimated relative risk information Any Abd. Pelv. Kaplan 150/150 Interview 1.5 USA 125/125 Interview 1.3 Polhemus et al. 251/251 Questionnaire 1.2 Canada Graham et al. 313/854 Medical records USA Salonen et al. 373/373 Medical records Finland Hirayama et al. 4,607/5,968 Not provided 1.6 Japan Monson et al. 704/14,294 Medical records USA Shu et al. 166/166 Interview 2.4 China Infante Rivard et al. 701/701 Interview 0.8 Canada

17 Risks for Childhood Brain Tumors with ihexposure to in Utero Diagnostic i Rdi Radiationi Authors, country Cases/Cont. Source of X ray Estimated relative risk information Any Abd. Pl Pelv. Bithell et al. 1,332/8,523 Interview, records, UK questionnaire Salonen et al. 245/245 Medical records Finland Preston et al. 209/209 Interview 1.3 USA Monson et al. 298/14,294 Medicalrecords 1.2 USA Schuz et al. 466/2,458 Interview 0.8 Germany

18 Risks for Childhood Leukemia and Brain Tumors with Exposure to in Utero Diagnostic Radiation Several studies have assessed risks for all types of childhoodleukemiacombined, leukemia combined, andreported elevated risks ranging from a 1.2 to 1.9 fold increased occurrence of leukemia in offspring of mothers who had received diagnostic radiographs to the abdominal region. On the other hand, six case control studies reported risks of pediatric brain tumors in offspring of mother undergoing diagnostic radiologic procedures with abdominal radiation exposures. Odds ratio ranged from 0.8 to 1.4 with no increases.

19 Risk of Childhood Cancers in Offspring of Women Undergoing Prenatal Diagnostic X rays Type of cancer Total number of deaths No. deaths associated with prenatal X rays Estimated relative risk (95% CI) Lymphatic leukemia 2, ( ) Myeloid leukemia ( ) Other & unspecified leukemia 1, ( ) Lymphoma ( ) Wilms tumor ( ) Central nervous system tumors 1, ( ) Neuroblastoma ( ) Bone ( ) All leukemias 4, ( ) All solid tumors 4, ( ) All childhood cancers 8,513 1, ( )

20 Risk of Childhood Cancers in Offspring of Women Undergoing Prenatal Diagnostic X rays The Oxford Survey of Childhood Cancers (OSCC) reported odds ratio of 1.6, 1.5 and 1.1 respectively, for Wilms tumor, neuroblastoma, and bone tumors, and odds ratios ranging from 1.4 to 1.6 for other pediatric cancers in offspring of mothers who underwent diagnostic medical examinations involving exposure to the abdomen during pregnancy.

21 Risks of Childhood Cancer according to the Trimester of Prenatal Diagnostic X ray Exposure Trimester of exposure Fetal age (wks) Cases/Cont Odds Radio First trimester / Second trimester / Third trimester ,317/1,

22 Risksof Pediatric Cancer by Trimester Although most of the case control studies limited assessmentto to querying about a history of anydiagnostic medical radiologic examination at any anatomic site during pregnancy, severaldata showed that most of the diagnostic radiologic procedures were performed in the third trimester of pregnancy, but the excess risks of childhood cancer were associated only with medical radiation exposure in the firsttrimester trimester.

23 Prenatal Sonography and Pediatric Cancer Risks On the other hand, as sonography began to replace obstetrical abdominal radiography and pelvimetry in evaluation of fetal growth, abnormalities and medical aspects related to delivery, concerns arose about potential ilcarcinogenicity i i of sonography examinations. Case control studies in several countries showed that no evidence of an excess of childhood leukemia or solid tumors in offspring of mothers undergoing sonography during pregnancy.

24 Postnatal Diagnostic Radiation and Pediatric Cancer Risks

25 Postnatal Diagnostic Radiation and Pediatric Cancer Risks In general, compared to the potential carcinogenic effects in utero radiation exposure on childhood cancer, the effects of postnatal diagnostic exposure have been much less studied.

26 Risks for All Pediatric Cancers Combined with Exposure to Early Life Diagnostic Radiation Authors, country Cases/Cont. Estimated relative risk Stewart et al. 1,299/1, (diagnostic) UK 2.7 (therapeutic) Hartley et al. 535/1, UK 465/ Shu et al. 642/ China

27 Risks for All Pediatric Cancers Combined with Exposure to Early Life Diagnostic Radiation UK study noted no association between early life diagnostic exposure and risk of all childhood cancers. Although another UK study observed a non statistically significantassociationassociation between childhood cancer risk and diagnostic radiation, this association disappeared when medical records data were used, suggesting the possibility of reporting bias.

28 Risks for Childhood Leukemia with Exposure to Early Life Diagnostic Radiation Authors, country Cases/Cont. Estimated relative risk Stewart et al. 619/619 12(Diagnostic) 1.2 UK 5.0 (Therapeutic) Polhemus et al. 251/ (Diagnostic) USA 3.5 (Fluoroscopy) 3.7 (Therapeutic) Ager et al. 109/ USA Graham et al. 319/ (anyexposure) USA 2.1 (>1 site exposure) Shu et al. 309/ China, Shanghai Fajardo Gutierrez et al. 79/ Mexico

29 Risks for Childhood Leukemia with Exposure to Early Life Diagnostic Radiation While a few studies detected a significantly elevated risk of leukemia with exposure to diagnostic radiation during childhood, these studies used questionnaire i data to assess exposure to diagnostic radiographs. Other investigations, including studies using medical records to verify X ray exposure did not report significantly increased risk of leukemia.

30 Risks for Childhood Brain Tumors with Exposure to Early Life Diagnostic Radiation Authors, country Cases/Cont. Estimated relative risk Howe et al. 74/ (Chest diagnostic) Canada 67(Skull 6.7 diagnostic) McCredie et al. 82/ (Dental) Australia 2.3 Shu et al. 107/ China Schuz et al. 466/2, Germany

31 Risks for Childhood Brain Tumors and Other Cancers with Exposure to Early Life Diagnostic Radiation In general, studies of diagnostic radiograph examinations and risk of childhood brain tumors have not observed an increased risk with exposure. While other specific cancer sites have been less studied, no consistent association has been observed for diagnostic radiation exposure and risk of childhood lymphoma, osteosarcoma, Ewing sarcoma, soft tissue sarcoma, or neuroblastoma.

32 Postnatal Diagnostic Radiation and Pediatric Cancer Risks Overall, there is very little evidence that exposure to postnatal diagnostic increases childhood cancer risk. However, it is noteworthy that repeated exposure to diagnostic exams during adolescence has been associated with increased risk of breast cancer later in life in patients with scoliosis. If a small increased risk of cancer due to diagnostic radiation exposure exists, most studies are not adequately powered or have limited assessment of childhood and adolescent cancer occurrence, and thus failed to be able to detect onset of cancer later in life.

33 Clinical and Public Health Policy Implications 1. An important issue for clinical practice is whether radiologic machine exposure settings have been appropriately adjusted for pediatric patients. More efforts should be given to development of standerized protocols for optimizing exposure settings exposure settings according to patient size and clinical indication for a given examination.

34 Clinical and Public Health Policy Implications 2. From policy perspective, referrers, radiologists and radiographers should make every effort to reduce the types and numbers of unnecessary radiologic procedures. Strengthening of public awareness is required to better inform parents, patients and consumers about the risks and benefits of diagnostic imaging.

35 Clinical and Public Health Policy Implications 3. Actions are needed from academic institutions to include radiation sciences and radiation protection topics into undergraduate and post graduate curricula to all users of radiation in medicine; i and international organizations and professional bodies to provide recommendations, standardized protocols and practical training to the end users to reduce radiation exposures.

36 Summary Information on cancer risks associated with diagnostic medical radiation during early childhood is still limited. Because of the dramatic increase in the numbers of children undergoing CT examinations, it is urgent to study occurrence of pediatric, adolescent, and adult cancer risks associated with these procedures. Newly projected investigations are definitely needed to obtain a novel information in this field.

Understanding radiation-induced cancer risks at radiological doses

Understanding radiation-induced cancer risks at radiological doses David J. Brenner Center for Radiological Research Columbia University Medical Center New York, NY djb3@columbia.edu Let s distinguish