Diagnostic Imaging and Diagnostic Imaging and Malignancy RiskMalignancy Risk

Emergency Medicine Grand RoundsEmergency Medicine Grand Rounds June 12, 2008June 12, 2008Dr. Jay GreenDr. Jay Green

Emergency Medicine Resident, PGY-2Emergency Medicine Resident, PGY-2

ObjectivesObjectives Learn basic radiation/radiobiology Learn basic radiation/radiobiology

principlesprinciples Learn what the diagnostic imaging Learn what the diagnostic imaging

literature says about imaging and cancerliterature says about imaging and cancer Discuss evidence from other sources Discuss evidence from other sources

about the cancer risks of radiationabout the cancer risks of radiation How these sources quantify this riskHow these sources quantify this risk

Discuss how this information should Discuss how this information should translate to patient caretranslate to patient care

CaseCase

18M presents @ 210018M presents @ 2100 Typical story for appendicitisTypical story for appendicitis Mild Mild ↑WBC↑WBC Call general surgeryCall general surgery

Ask you to get a CT scan and call backAsk you to get a CT scan and call back

Local dataLocal data

FMC EDFMC ED 15% of patients get a CT15% of patients get a CT 18 000 ED CT scans/year18 000 ED CT scans/year

FMC, PLC, RGHFMC, PLC, RGH Unable to use proper pediatric CT dosesUnable to use proper pediatric CT doses

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

Basics of radiation/radiobiologyBasics of radiation/radiobiology

Radiation induced tissue damage Radiation induced tissue damage DirectDirect

Damaging DNA, RNA, enzymesDamaging DNA, RNA, enzymes IndirectIndirect

Creating free radicalsCreating free radicals

Most radiosensitive tissuesMost radiosensitive tissues Bone marrow, thyroid, breast, lungBone marrow, thyroid, breast, lung

Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

Basics of radiation/radiobiologyBasics of radiation/radiobiology

Some unitsSome units Gray (Gy)Gray (Gy)

Absorbed doseAbsorbed dose Energy absorbed per unit mass at specific point Energy absorbed per unit mass at specific point

(J/kg)(J/kg) Sieverts (Sv)Sieverts (Sv)

Effective doseEffective dose Weighted average of organ dosesWeighted average of organ doses Whole-body equivalent Whole-body equivalent

McNitt-Gray. AAPM/RSNA Physics tutorial for residents: topics in CT. Radiographics 2002;22(6):1541-53

Some doses and effectsSome doses and effects 10,000mSv10,000mSv

Radiation sickness, death within weeksRadiation sickness, death within weeks 1,000mSv1,000mSv

Radiation sickness, unlikely to cause deathRadiation sickness, unlikely to cause death 100-1000mSv100-1000mSv

Dose related increasing risk of carcinogenesisDose related increasing risk of carcinogenesis 50mSv50mSv

Clearly associated with increased cancer risk and the highest dose allowed Clearly associated with increased cancer risk and the highest dose allowed yearly in occupational exposureyearly in occupational exposure

20mSv/year averaged over 5 years20mSv/year averaged over 5 years Highest allowable dose for radiation workersHighest allowable dose for radiation workers

5mSv acute dose5mSv acute dose Reasonable evidence for increase in some cancersReasonable evidence for increase in some cancers

3-5mSv/year3-5mSv/year Typical dose rates of uranium miners in Australia and CanadaTypical dose rates of uranium miners in Australia and Canada

0.3mSv0.3mSv Round trip flight NY to LondonRound 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

Typical radiological proceduresTypical radiological proceduresProcedureProcedure Effective DoseEffective Dose

CXRCXR 0.1mSv0.1mSvInfant VCUGInfant VCUG 0.8mSv0.8mSv

CT HeadCT Head 2mSv2mSvCardiac cathCardiac cath 2.5mSv2.5mSv

CT ChestCT Chest 8mSv8mSvCTPACTPA 8mSv8mSv

CT KUBCT KUB 10mSv10mSvCT Abdo/PelvisCT Abdo/Pelvis 10mSv10mSvPeds CT abdoPeds CT abdo 25mSv25mSvPeds CT headPeds CT head 30mSv30mSv

Radiation dose typeRadiation dose type

Fractionated vs acute dosesFractionated vs acute doses Human dataHuman data

No difference in radiosensitive tissuesNo difference in radiosensitive tissues Animal dataAnimal data

Risk of fractionated exposure is lessRisk of fractionated exposure is less

Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol 2002;32:232-7

Are estimates from other radiation sources Are estimates from other radiation sources applicable to CT scans?applicable to CT scans?

EM radiationEM radiation

X-rays X-rays Extranuclear originExtranuclear origin

Gamma raysGamma rays Intranuclear originIntranuclear origin

Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

Electromagnetic radiationElectromagnetic radiation

Two basic forms of radiationTwo basic forms of radiation X-raysX-rays Gamma raysGamma rays

Both forms of EM radiationBoth forms of EM radiation Only difference is frequency (Hz) or Only difference is frequency (Hz) or

energy (eV)energy (eV)

Bushberg et al. The Essential Physics of Medical Imaging. Williams & Wilkins Maryland. 1994

EM radiation spectrumEM 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

What does the literature say about What does the literature say about diagnostic imaging causing cancer?diagnostic imaging causing cancer?

American College of RadiologyAmerican College of Radiology

Difficulties with researchDifficulties with research Radiation-induced cancers delayed 1-2 Radiation-induced cancers delayed 1-2

decadesdecades Lifetime incidence of CA is 40%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

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

Ongoing researchOngoing research

No epidemiological data on CT scansNo epidemiological data on CT scans UK epidemiological study ongoingUK epidemiological study ongoing

Pearce & Parker, University of Newcastle Pearce & Parker, University of Newcastle upon Tyneupon Tyne

N=100,000N=100,000 Too early for any resultsToo early for any results

Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol 2002;32:232-7

In uteroIn utero

Risk to fetus initially described in 1956Risk to fetus initially described in 1956 Case-control studiesCase-control studies

Consistent association since 1956Consistent association since 1956 US hospital chart reviews confirm thisUS hospital chart reviews confirm this

AXR has RR 1.39 (1.3-1.5) for childhood CAAXR has RR 1.39 (1.3-1.5) for childhood CA N=15,000N=15,000

Confirmed in other studiesConfirmed in other studies

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

Potential dose responsePotential dose response

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

BUT…BUT…

Atomic bomb dataAtomic bomb data No increase risk to fetus of exposed mothersNo increase risk to fetus of exposed mothers

N=1263N=1263 Loss of follow-up in early years after bombLoss of follow-up in early years after bomb

Small cohort studies show no relationshipSmall cohort studies show no relationship

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

TB surveillanceTB surveillance

Massachusetts 1925-1954Massachusetts 1925-1954 4940 women treated for TB4940 women treated for TB

2573 received avg 88 fluoro exams2573 received avg 88 fluoro exams Followed for 30 yearsFollowed 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

ResultsResults

Younger = higher riskYounger = higher risk Risk of fractionated doses similar to single doseRisk of fractionated doses similar to single dose Similar results to other studiesSimilar 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

Pediatric CTPediatric CT

Pediatric CT different than adultPediatric CT different than adult Organ doses higherOrgan doses higher Increasing frequency faster than adultsIncreasing frequency faster than adults Children more radiosensitiveChildren more radiosensitive

More time to express cancerMore time to express cancer More dividing cellsMore dividing cells Females>malesFemales>males

Need different scanner settingsNeed different scanner settings

Brenner DJ. Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002;32:228-31

Brenner DJ. Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002;32:228-31

<20yo risk 1/800-1/2000

Pediatric CT riskPediatric CT risk

Complex modeling used to estimate riskComplex modeling used to estimate risk Peds risk much higher than adultPeds risk much higher than adult

~10-15x higher~10-15x higher

Brenner et al. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR 2001;176:289-96

Brenner et al. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR 2001;176:289-96

Pediatric CT riskPediatric CT risk

600,000 kids CT scanned/year600,000 kids CT scanned/year 140,000 will eventually die from CA140,000 will eventually die from CA

500 CA deaths attributable to CT500 CA deaths attributable to CT 1/12001/1200 risk that peds CT will cause fatal CA 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 1yoStudy in 1yo Cancer MortalityCancer Mortality

CT AbdomenCT Abdomen 1/5501/550

CT HeadCT Head 1/15001/1500

Risk in adultsRisk in adults

Used population data and modelsUsed population data and models Many assumptions Many assumptions considerable considerable

uncertaintyuncertainty Some calculations use atomic bomb dataSome calculations use atomic bomb data

ResultsResults In CanadaIn Canada

Risk of CA from imaging ~Risk of CA from imaging ~1/4501/450 (UK ~ (UK ~ 1/8001/800)) 784 cases of cancer per year 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

Risk from full-body CT screeningRisk from full-body CT screening

Risk estimationRisk estimation Use atomic bomb data in estimatesUse atomic bomb data in estimates Dose = 12mSvDose = 12mSv ResultsResults

Single CT body in 45yo = Single CT body in 45yo = 1/12501/1250 mortality risk mortality risk

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

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

25yo = 1/740

45yo = 1/1250

65yo = 1/1700

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

Is there applicable evidence from other Is there applicable evidence from other sources about the cancer risks of low dose sources about the cancer risks of low dose radiation?radiation?

How do these sources quantify this risk?How do these sources quantify this risk?

Atomic bomb dataAtomic bomb data

DifferencesDifferences One-time exposureOne-time exposure Mostly gamma radiationMostly gamma radiation

ButBut Include data on subjects exposed to similar Include data on subjects exposed to similar

doses to diagnostic imagingdoses to diagnostic imaging

Atomic bomb dataAtomic bomb data

N~30,000 dose range 5-100mSvN~30,000 dose range 5-100mSv 4119 solid cancers4119 solid cancers

77 cancers more than predicted77 cancers more than predicted 1/7141/714 risk of death from radiation in this risk of death from radiation in this

rangerange

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

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

Nuclear industryNuclear industry

N=407,391, radiation monitored externallyN=407,391, radiation monitored externally Predominantly gamma raysPredominantly gamma rays Average cumulative dose 19mSvAverage cumulative dose 19mSv ResultsResults

1-2% of CA deaths attributable to radiation1-2% of CA deaths attributable to radiation Similar estimates to atomic bomb Similar estimates to atomic bomb

cohortcohort

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

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

How does/should this translate to patient How does/should this translate to patient care?care?

Awareness of riskAwareness of risk Survey of 76 abdo/pelvic CT patientsSurvey of 76 abdo/pelvic CT patients AskedAsked

Informed about risks, benefits, radiation doseInformed about risks, benefits, radiation dose Did they believe scan increased CA riskDid they believe scan increased CA risk

ResultsResults 7% told about risks of CT7% told about risks of CT

22% of EP’s22% of EP’s 3% believed scan increased CA risk3% believed scan increased CA risk

9% of EP’s, 47% of radiologists9% 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

Informed consentInformed consent US academic medical centersUS academic medical centers Survey of chairmen of radiology deptsSurvey of chairmen of radiology depts ResultsResults

Lee et al. Diagnostic CT scans: institutional informed consent guidelines and practices at academic medical centres. AJR 2006;187:282-7.

““Can sue your doctor if you believe you’ve Can sue your doctor if you believe you’ve been exposed to an excess amount of been exposed to an excess amount of radiation”radiation”

Injuryboard.comInjuryboard.com

Take-home pointsTake-home points Risk of fatal CA from imaging 1/500-1/1500Risk of fatal CA from imaging 1/500-1/1500

Risk more significant in young (<30yo)Risk more significant in young (<30yo)

More awareness neededMore awareness needed

Risk discussion with patientsRisk discussion with patients

Informed consent?Informed consent?

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

ReferencesReferencesCardis E et al. The 15-country collaborative study of cancer risk among radiation workersin the nuclear industry. Radiat Res 2007;167:396-416Cardis E et al. Risk of cancer after low doses of ionising radiation: retrospective cohortstudy in 15 countries. BMJ 2005;331:77-82Clemons M et al. Breast cancer risk following irradiation for Hodgkin’s disease. CancerTreatment Reviews 2000;26:291-302Doll R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997;70:130-9Giles J. Study warns of ‘avoidable’ risks of CT scans. Nature 204;431:391Lee et al. Diagnostic CT scans: assessment and patient, physicia, and radiologistawareness of radiation dose and possible risks. Radiology 2004;231:393-8Lee et al. Diagnostic CT scans: institutional informed consent guidelines and practices atacademic medical centres. AJR 2006;187:282-7.McNitt-Gray. AAPM/RSNA Physics tutorial for residents: topics in CT. Radiographics2002;22(6):1541-53 Panel discussion: section 1: helical CT and cancer risk. Pediatr Radiol 2002;32:242-4Pierce DA & Preston DL. Radiation-related cancer risks at low doses among atomicbomb survivors. Radiat Res 2000;154:178-86 Preston DL et al. Studies of mortality of atomic bomb survivors. Report 13: solid cancerand noncancer disease mortality: 1950-1997. Radiat Res 2003;160:381-407Preston DL et al. Solid cancer incidence in atomic bomb survivors: 1958-1998. RadiatRes 2007;168:1-64Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Pediatr Radiol2002;32:232-7

Questions?Questions?