1. Diagnostic Imaging and Malignancy Risk Emergency Medicine Grand Rounds June 12, 2008 June 12, 2008 Dr. Jay Green Emergency Medicine Resident, PGY-2

2. Objectives  Learn basic radiation/radiobiology principles  Learn what the diagnostic imaging literature says about imaging and cancer  Discuss evidence from other sources about the cancer risks of radiation  How these sources quantify this risk  Discuss how this information should translate to patient care

3. Case  18M presents @ 2100  Typical story for appendicitis  Mild ↑WBC  Call general surgery  Ask you to get a CT scan and call back

4. Local data  FMC ED  15% of patients get a CT  18 000 ED CT scans/year  FMC, PLC, RGH  Unable to use proper pediatric CT doses

5.  What radiation/radiobiology principles are important to consider in this discussion?

6. Basics of radiation/radiobiology  Radiation induced tissue damage  Direct  Damaging DNA, RNA, enzymes  Indirect  Creating free radicals  Most radiosensitive tissues  Bone marrow, thyroid, breast, lung Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

7. Basics of radiation/radiobiology  Some units  Gray (Gy)  Absorbed dose  Energy absorbed per unit mass at specific point (J/kg)  Sieverts (Sv)  Effective dose  Weighted average of organ doses  Whole-body equivalent McNitt-Gray. AAPM/RSNA Physics tutorial for residents: topics in CT. Radiographics 2002;22(6):1541-53

8. Some doses and effects  10,000mSv  Radiation sickness, death within weeks  1,000mSv  Radiation sickness, unlikely to cause death  100-1000mSv  Dose related increasing risk of carcinogenesis  50mSv  Clearly associated with increased cancer risk and the highest dose allowed yearly in occupational exposure  20mSv/year averaged over 5 years  Highest allowable dose for radiation workers  5mSv acute dose  Reasonable evidence for increase in some cancers  3-5mSv/year  Typical dose rates of uranium miners in Australia and Canada  0.3mSv  Round trip flight NY to London Brenner DJ et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Nat Assoc Sci 2003;100(24):13761-6

9. Typical radiological procedures Procedure Effective Dose CXR0.1mSv Infant VCUG 0.8mSv CT Head 2mSv Cardiac cath 2.5mSv CT Chest 8mSv CTPA8mSv CT KUB 10mSv CT Abdo/Pelvis 10mSv Peds CT abdo 25mSv Peds CT head 30mSv

10. Radiation dose type  Fractionated vs acute doses  Human data  No difference in radiosensitive tissues  Animal data  Risk of fractionated exposure is less Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol 2002;32:232-7

11.  Are estimates from other radiation sources applicable to CT scans?

12. EM radiation  X-rays  Extranuclear origin  Gamma rays  Intranuclear origin Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

13. Electromagnetic radiation  Two basic forms of radiation  X-rays  Gamma rays  Both forms of EM radiation  Only difference is frequency (Hz) or energy (eV) Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

14. EM radiation spectrum Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994 Gamma rays X-rays Ultraviolet Visible light eV or Hz

15.  What does the literature say about diagnostic imaging causing cancer?

16. American College of Radiology  Difficulties with research  Radiation-induced cancers delayed 1-2 decades  Lifetime incidence of CA is 40% Amis ES et al. American College of Radiology White Paper on Radiation Dose in Medicine. Journal Am Coll Rad 2007

17. Brenner DJ et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Nat Assoc Sci 2003;100(24):13761-6

18. Ongoing research  No epidemiological data on CT scans  UK epidemiological study ongoing  Pearce & Parker, University of Newcastle upon Tyne  N=100,000  Too early for any results Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol 2002;32:232-7

19. In utero  Risk to fetus initially described in 1956  Case-control studies  Consistent association since 1956  US hospital chart reviews confirm this  AXR has RR 1.39 (1.3-1.5) for childhood CA  N=15,000  Confirmed in other studies Doll R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130-9

20. Potential dose response Doll R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130-9

21. BUT…  Atomic bomb data  No increase risk to fetus of exposed mothers  N=1263  Loss of follow-up in early years after bomb  Small cohort studies show no relationship Doll R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130-9

22. TB surveillance  Massachusetts 1925-1954  4940 women treated for TB  2573 received avg 88 fluoro exams  Followed for 30 years Boice JD et al. Frequent Chest X-Ray Fluoroscopy and Breast Cancer Incidence among Tuberculosis Patients in Massachusetts. Radiat Res 1991;125(2):214-22

23. Results  Younger = higher risk  Risk of fractionated doses similar to single dose  Similar results to other studies Boice JD et al. Frequent Chest X-Ray Fluoroscopy and Breast Cancer Incidence among Tuberculosis Patients in Massachusetts. Radiat Res 1991;125(2):214-22 Davis FG. Cancer Res 1989;49:6130 Hildreth NG. NEJM 1989;321:1281

24. Pediatric CT  Pediatric CT different than adult  Organ doses higher  Increasing frequency faster than adults  Children more radiosensitive  More time to express cancer  More dividing cells  Females>males  Need different scanner settings Brenner DJ. Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002;32:228-31

25. <20yo risk 1/800-1/2000

26. Pediatric CT risk  Complex modeling used to estimate risk  Peds risk much higher than adult  ~10-15x higher Brenner et al. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR 2001;176:289-96

28. Pediatric CT risk  600,000 kids CT scanned/year  140,000 will eventually die from CA  500 CA deaths attributable to CT  1/1200 risk that peds CT will cause fatal CA Brenner et al. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR 2001;176:289-96 Study in 1yo Cancer Mortality CT Abdomen 1/550 CT Head 1/1500

29. Risk in adults  Used population data and models  Many assumptions  considerable uncertainty  Some calculations use atomic bomb data  Results  In Canada  Risk of CA from imaging ~1/450 (UK ~ 1/800)  784 cases of cancer per year Berrington & Darby. Risk of cancer from diagnostic x-rays: estimates for the UK and 14 other countries. Lancet 2004;363:345-51

30. Risk from full-body CT screening  Risk estimation  Use atomic bomb data in estimates  Dose = 12mSv  Results  Single CT body in 45yo = 1/1250 mortality risk Brenner DJ & Elliston CD. Estimated radiation risks potentially associted with full-body CT scanning. Radiology 2004;232:735-8

31. 25yo = 1/740 45yo = 1/1250 65yo = 1/1700

32. Brenner DJ & Elliston CD. Estimated radiation risks potentially associted with full-body CT scanning. Radiology 2004;232:735-8

33.  Is there applicable evidence from other sources about the cancer risks of low dose radiation?  How do these sources quantify this risk?

34. Atomic bomb data  Differences  One-time exposure  Mostly gamma radiation  But  Include data on subjects exposed to similar doses to diagnostic imaging

35. Atomic bomb data  N~30,000 dose range 5-100mSv  4119 solid cancers  77 cancers more than predicted  1/714 risk of death from radiation in this range Pierce DA & Preston DL. Radiation-related cancer risks at low doses among atomic bomb survivors. Radiat Res 2000;154:178-86 Preston DL et al. Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950-1997. Radiat Res 2003;160:381-407

36. Brenner DJ. Estimates of the cancer risks from pediatric CT radiation are not merely theoretical: comment on 0094-2405. Medical Physics 2001;28(11):2387-8

37. Nuclear industry  N=407,391, radiation monitored externally  Predominantly gamma rays  Average cumulative dose 19mSv  Results  1-2% of CA deaths attributable to radiation  Similar estimates to atomic bomb cohort Cardis E et al. The 15-country collaborative study of cancer risk among radiation workers in the nuclear industry. Radiat Res 2007;167:396-416 Cardis E et al. Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ 2005;331:77-82

38.  When is ED CT optional?  Renal colic?  Classic appendicitis?  Trauma pan-scan?

39.  How does/should this translate to patient care?

40. Awareness of risk  Survey of 76 abdo/pelvic CT patients  Asked  Informed about risks, benefits, radiation dose  Did they believe scan increased CA risk  Results  7% told about risks of CT  22% of EP’s  3% believed scan increased CA risk  9% of EP’s, 47% of radiologists Lee et al. Diagnostic CT scans: assessment and patient, physician, and radiologist awareness of radiation dose and possible risks. Radiology 2004;231:393-8

41. Informed consent  US academic medical centers  Survey of chairmen of radiology depts  Results Lee et al. Diagnostic CT scans: institutional informed consent guidelines and practices at academic medical centres. AJR 2006;187:282-7.

42.  “Can sue your doctor if you believe you’ve been exposed to an excess amount of radiation” Injuryboard.com

43. Take-home points  Risk of fatal CA from imaging 1/500-1/1500  Risk more significant in young (<30yo)  More awareness needed  Risk discussion with patients  Informed consent?

44. References Amis ES et al. American College of Radiology White Paper on Radiation Dose in Medicine. Journal Am Coll Rad 2007 Berrington & Darby. Risk of cancer from diagnostic x-rays: estimates for the UK and 14 other countries. Lancet 2004;363:345-51 Boice JD et al. Frequent Chest X-Ray Fluoroscopy and Breast Cancer Incidence among Tuberculosis Patients in Massachusetts. Radiat Res 1991;125(2):214-22 Brenner & Hall. Computer tomography – an increasing source of radiation exposure. NEJM 2007;357(22):2277-84 Brenner DJ. Estimates of the cancer risks from pediatric CT radiation are not merely theoretical: comment on 0094-2405. Medical Physics 2001;28(11):2387-8 Brenner DJ et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Nat Assoc Sci 2003;100(24):13761-6 Brenner DJ. Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002;32:228-31 Brenner et al. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR 2001;176:289-96 Brenner DJ. Radiation risks potentially associated with low-dose CT screening of adult smokers for lung cancer. Radiology 2004;231:440-5 Brenner DJ & Elliston CD. Estimated radiation risks potentially associted with full-body CT scanning. Radiology 2004;232:735-8 Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

45. References Cardis E et al. The 15-country collaborative study of cancer risk among radiation workers in the nuclear industry. Radiat Res 2007;167:396-416 Cardis E et al. Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ 2005;331:77-82 Clemons M et al. Breast cancer risk following irradiation for Hodgkin’s disease. Cancer Treatment Reviews 2000;26:291-302 Doll R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130-9 Giles J. Study warns of ‘avoidable’ risks of CT scans. Nature 204;431:391 Lee et al. Diagnostic CT scans: assessment and patient, physicia, and radiologist awareness of radiation dose and possible risks. Radiology 2004;231:393-8 Lee et al. Diagnostic CT scans: institutional informed consent guidelines and practices at academic medical centres. AJR 2006;187:282-7. McNitt-Gray. AAPM/RSNA Physics tutorial for residents: topics in CT. Radiographics 2002;22(6):1541-53 Panel discussion: section 1: helical CT and cancer risk. Pediatr Radiol 2002;32:242-4 Pierce DA & Preston DL. Radiation-related cancer risks at low doses among atomic bomb survivors. Radiat Res 2000;154:178-86 Preston DL et al. Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950-1997. Radiat Res 2003;160:381-407 Preston DL et al. Solid cancer incidence in atomic bomb survivors: 1958-1998. Radiat Res 2007;168:1-64 Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol 2002;32:232-7

46. Questions?