Treating Thyroid Treating Thyroid Cancer using Cancer using

II--131 Maximum 131 Maximum Tolerable Dose Tolerable Dose

Method Method Christopher Martel, M.Sc., CHPChristopher Martel, M.Sc., CHPLisa Lisa ThornhillThornhill, NRRPT, RT(NM), NRRPT, RT(NM)Boston University Medical CenterBoston University Medical Center

Thyroid CarcinomaThyroid Carcinoma

New cases and deaths in the U.S., 2007New cases and deaths in the U.S., 2007New Cases New Cases –– 33,55033,550Deaths Deaths -- 1,5301,530

Risk factors that increase chances Risk factors that increase chances 1) White female, over 40 y.o. 1) White female, over 40 y.o. 2) Genetic (for 2) Genetic (for medullarymedullary thyroid carcinoma)thyroid carcinoma)3) Not enough iodine in the diet3) Not enough iodine in the diet4) Radiation and/or radioactive fallout4) Radiation and/or radioactive fallout

National Cancer Institute, http://www.cancer.gov/

Thyroid Cancer Incidence Rates

Thyroid Cancer Incidence RatesThyroid Cancer Incidence Rates

National Cancer Institute, http://www.cancer.gov/

Methods of TreatmentMethods of Treatment

Depending on type and stage of the cancer:Depending on type and stage of the cancer:1) surgery1) surgery2) radioactive iodine2) radioactive iodine3) hormone therapy 3) hormone therapy 4) external radiation4) external radiation5) chemotherapy5) chemotherapy

Maxon,HR J Nuclear Med, 1992; 33:1132-1136

1.1. post surgery for thyroid removalpost surgery for thyroid removal2.2. related to tumor’s future capacity to concentrate iodinerelated to tumor’s future capacity to concentrate iodine3.3. positive relationship between total Ipositive relationship between total I--131 uptake per 131 uptake per

tumor mass and outcome tumor mass and outcome –– but not proven for maximal but not proven for maximal dosesdoses

** doses < 35 ** doses < 35 GyGy to tumor likely will not respond to to tumor likely will not respond to II--131 therapy need 300 131 therapy need 300 GyGy to thyroid remnant, 120 to thyroid remnant, 120 GyGyto to metastaticmetastatic focifoci

Radioactive Iodine Therapy

Radioiodine Uptake RangesRadioiodine Uptake Ranges

Radioiodine is used to Radioiodine is used to determine thyroid determine thyroid uptake.uptake.Isotopes used include Isotopes used include II--123 and I123 and I--131.131.Normal uptake 15Normal uptake 15--25%25%Hypo Hypo –– <10%<10%Hyper Hyper -- >30%>30%

Images of Thyroid Cancer

WB PET Scan with FDG

WB Nuclear Med Scan with Tl-201

Surgical Tumor Removal

Iodine Kinetics (simplified)Iodine Kinetics (simplified)

3

1 2

4

K21 = 0.114

K32 = 0.002

K42 = 0.007

K14 = 0.1

K04 = 0.018

K13 = 0.56

feces

T4

K12 = 0.005

K01 = 2

I-

urine

thyroid

T3

Estimated % of Administered IEstimated % of Administered I--

3.1

ExcretedOtherLiver (1.4)Thyroid (1.5)Intestine

Blood

Stomach

ECEV

7.9

14.7

42.4

13.6

15.4 2.0

6.9

9.0

25.9

8.3

OtherLiverThyroidIntestine

Excreted

Blood

Stomach

ECEV

9.4

37.6

1 hour 6 hours 24 hours

4.6

13.8

Excreted

OtherLiver

ThyroidIntestine 1.6Blood 1.6Stomach 1.4ECEV

76.1

MIRD Dose Estimate Report No. 5 (Maximum thyroid uptake of 15%)

II--131 Review 131 Review

physical halfphysical half--life of 8..06 dayslife of 8..06 daysBeta emitterBeta emittermax energy 610 max energy 610 KeVKeV; ; avgavg energy 193 energy 193 KeVKeVtissue range of 0.8 mmtissue range of 0.8 mmGamma emitterGamma emitterprincipal energy 365 principal energy 365 KeVKeV (81%)(81%)

94% of radiation dose is from the beta emissions94% of radiation dose is from the beta emissions

IodineIodine--131 Decay Data131 Decay DataHalf life:Half life: 8.06 days8.06 days

EnergyEnergyEmissionsEmissions No.No. ((MevMev)) YieldYieldgammagamma 66 0.030.03 4.6%4.6%

0.080.08 2.6%2.6%0.2840.284 5.8%5.8%0.3640.364 63.6%63.6%0.6370.637 6.5%6.5%0.7230.723 2.6%2.6%

betabeta 33 0.2480.248 2.12%2.12%0.3340.334 7.36%7.36%0.6060.606 89.3%89.3%

SNM: Dose Selection SNM: Dose Selection General Guidelines for Thyroid

Cancer patientsFor postoperative ablation of thyroid bed remnants For postoperative ablation of thyroid bed remnants depending on the amount of functioning tissue presentdepending on the amount of functioning tissue present

(75 (75 –– 150 150 mCimCi))

For treatment of presumed thyroid cancer in the neck or For treatment of presumed thyroid cancer in the neck or mediastinalmediastinal lymph nodeslymph nodes

(150 (150 –– 200 200 mCimCi))

For treatment of distant metastases For treatment of distant metastases

(> 200 (> 200 mCimCi) *Candidate for MTD*) *Candidate for MTD*

Maximal Dose Therapy Maximal Dose Therapy Considered When Considered When

Patients with lifePatients with life--threatening diseasethreatening diseasePatients with progressive disease but little Patients with progressive disease but little response to previous treatmentsresponse to previous treatmentsPatients with bone Patients with bone mets mets Patients with nodal diseasePatients with nodal disease

Goal is to treat but not to cure diseaseGoal is to treat but not to cure disease

Why Perform Maximal Dose Why Perform Maximal Dose Therapy ? Therapy ?

Standard treatment using empiric guidelines is only a “best Standard treatment using empiric guidelines is only a “best guess”guess”and not truly tailored for each patientand not truly tailored for each patient

Better outcome if treated with one rather than multipleBetter outcome if treated with one rather than multipleII--131 treatments131 treatments

Common Side Effects from Common Side Effects from >200 >200 mCimCi Dose IDose I--131 Therapy131 Therapy

6060--70% radiation sickness70% radiation sickness1010--15% 15% sialoadenitissialoadenitis10% 10% leukopenialeukopenia for up to one yearfor up to one year70% transient 70% transient azoospermiaazoospermiaCystitis, radiation Cystitis, radiation thyroiditisthyroiditis, gastritis, transient , gastritis, transient loss of tasteloss of taste

Absorbed Dose Calculations Absorbed Dose Calculations Uses Modification to the MIRD Uses Modification to the MIRD

SystemSystem

“Practical Determination of Patient“Practical Determination of Patient--Specific Marrow Specific Marrow Dose Using Radioactivity Concentration in Blood Dose Using Radioactivity Concentration in Blood and Body”and Body”

ShenShen, , DenardoDenardo SgourosSgouros, et. al, et. alUC Davis/Memorial SloanUC Davis/Memorial Sloan--Kettering Cancer InstituteKettering Cancer InstituteJournal of Nuclear Medicine, Journal of Nuclear Medicine, VolVol 40, No. 12 December 199940, No. 12 December 1999

Critical Factors in Calculating Patient Dose

Dose to red marrow– Red marrow self dose– Total body to red marrow dose

Dose to lungs– Whole body retention at 48 hours

Limiting Factors for Limiting Factors for Maximal IMaximal I--131 Dose Therapy131 Dose Therapy

Whole Body Retention at 48 hoursWhole Body Retention at 48 hours–– 80 80 mCimCi if lung metastases are presentif lung metastases are present–– 120 120 mCimCi if lung if lung metsmets not presentnot present

Requires: WB counting using dual head Gamma CameraRequires: WB counting using dual head Gamma Camera

200 200 cGycGy (200 (200 RadsRads) absorbed dose to the red BM) absorbed dose to the red BM

Requires:Requires:WB countingWB countingblood samplingblood samplingmathematical modelingmathematical modeling

General Principles for Calculating Absorbed Dose

Give amount of radioactivity which will reside in a particular oGive amount of radioactivity which will reside in a particular organrgan

Must determine total # nuclear transformations that occur withinMust determine total # nuclear transformations that occur within that organthat organ1) activity (transition rate or decay rate) 1) activity (transition rate or decay rate) Physical characteristicsPhysical characteristics2) time that nuclide is resident in that organ 2) time that nuclide is resident in that organ Biologic characteristicsBiologic characteristics

Cumulated Activity (Cumulated Activity (mCimCi--hrs)hrs) = Activity (= Activity (mCimCi) in organ x time = () in organ x time = (mCimCi--hrs)hrs)

Divide the Cumulated Activity in the organ / Total given ActivitDivide the Cumulated Activity in the organ / Total given Activity to bodyy to body= total # nuclear transitions in organ per unit activity= total # nuclear transitions in organ per unit activity

This is also known as the This is also known as the Residence TimeResidence Time in the organ of interestin the organ of interest

Phantom Models in OLINDAPhantom Models in OLINDA--EXMEXM

70 kg adult (reference male)70 kg adult (reference male)57 kg (reference female)57 kg (reference female)57 kg 15 year old57 kg 15 year old32 kg 10 year old32 kg 10 year old19 kg 5 year old19 kg 5 year old9.2 kg 1 year old9.2 kg 1 year old3.4 kg newborn3.4 kg newborn

Biodistribution of I-131

For most radiopharmaceuticals, the activity in a For most radiopharmaceuticals, the activity in a given organ does not remain constant given organ does not remain constant throughout the period of interest throughout the period of interest –– radioactive (physical) decayradioactive (physical) decay–– ongoing biologic processes of uptake and removal of ongoing biologic processes of uptake and removal of

metabolitesmetabolites

Problems with Biodistribution

Patients have very different rates of metabolism, especially older or sicker patients

Patients with Thyroid Cancer have had their thyroids removed

Each lesion will have its own uptake and biological removal rate

Performing Maximal Dose IPerforming Maximal Dose I--131 131 TherapyTherapy

Administer tracer dose of IAdminister tracer dose of I--131 (~2131 (~2--3 3 mCimCi))Obtain blood samples at specific time Obtain blood samples at specific time intervalsintervalsObtain whole body images (gamma Obtain whole body images (gamma camera) at specific time intervalscamera) at specific time intervals

II--131 Dosimetry Chronological 131 Dosimetry Chronological StepsSteps

1. Patient is booked for the procedure HP needs name, medical record number, DOB, weight and recent hematocrit

2. Work must begin on a Monday, dosimetry done Monday-Friday

3. Patient gets dosed with the I-131 treatment the following Monday

4. Patient must stay in the hospital post treatment, usually upto five days

Day OneDay One

HOURS

0 1 2 3 4 5 6

BACKGROUNDIV insertedBlood drawWhole Body Count

Administer Iodine

NO VOIDBlood draw

Whole Body Count

VOIDBlood draw

Whole Body Count

VOIDBlood draw

Whole Body Count

Days 2 through 5Days 2 through 5

Day 2 (24 hr) – Blood draw and whole body count

Day 3 (48 hr) – Blood draw and whole body count

Day 4 (72 hr) – Blood draw and whole body count

Day 5 (96 hr) – Blood draw and whole body countDosimetry calculationsReview with MDOrder dose

Room Preparation for I-131 Radiotherapy Patient on 7W

Room 7W-26

Patient #1Patient #143 43 yoyo female with Papillary Thyroid Cancerfemale with Papillary Thyroid Cancer

01/28/2005 I01/28/2005 I--123 uptake focal nodal disease, four distinct areas within123 uptake focal nodal disease, four distinct areas withinneck region; total neck uptake 0.26 %neck region; total neck uptake 0.26 %

02/04/2005 I02/04/2005 I--131 Therapy Dose 196 131 Therapy Dose 196 mCimCi02/11/2005 WB scan, 7 days post I02/11/2005 WB scan, 7 days post I--131 therapy131 therapy

09/20/2005 I09/20/2005 I--131 WB dosimetry (five days)131 WB dosimetry (five days)09/27/2005 I09/27/2005 I--131 Therapy Dose 450 131 Therapy Dose 450 mCimCi10/07/2005 WB scan, 7 days post I10/07/2005 WB scan, 7 days post I--131 therapy131 therapy

90 minutes post ingestion intake90 minutes post ingestion intake

3 hours post ingestion intake3 hours post ingestion intake

5 hours post ingestion intake5 hours post ingestion intake

24 hours post ingestion intake24 hours post ingestion intake

48 hours post ingestion intake48 hours post ingestion intake

72 hours post ingestion intake72 hours post ingestion intake

I-131 WB scan 09/22/2005

96 hours post ingestion intake96 hours post ingestion intake

Patient #2Patient #260 yo female with metastatic papillary thyroid cancer to the lungs

06/06/2006 I-131 WB dosimetry (five days)Intense uptake in the thyroid bed; patchy uptakein both mid lung bases

06/28/2006 WB scan, 15 days post I-131 therapyFindings similar to previous dosimetry scans;In addition, iodine avid focus in right mid neck

Two hours Two hours post tracer post tracer dosedose

Four hours Four hours post tracer post tracer dosedose

24 hours 24 hours post tracer post tracer dosedose

48 hours 48 hours post tracer post tracer dosedose

72 hours 72 hours post tracer post tracer dosedose

Dosimetry ResultsDosimetry ResultsBlood Activity per Gram vs Time Post Administration

y = 0.0689e-0.061x

R2 = 0.9632

y = 0.278e-0.0738x

R2 = 0.9664

0.00000

0.01000

0.02000

0.03000

0.04000

0.05000

0.06000

0.07000

0.08000

0.00 20.00 40.00 60.00 80.00 100.00 120.00 140.00 160.00

Time (hours)

Blo

od A

ctiv

ity (u

Ci/g

m)

Exponential fit to all data

Exponential fit to last 3 data points

Exponential fitto all data

Exponential fitto last 3 data points

Exponential fit to all data

Exponential fit to last three data points

Whole Body Activity versus Time Post Administration

y = 2.6148e-0.0274x

R2 = 0.9318

y = 1.4122e-0.0163x

R2 = 0.9659

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

Time (Hours)

Act

ivity

(mC

i)

Exponential fit to all data

Exponential fit to last three data points

Administered352 mCi

THYROID ANTERIOR COUNTS

0

2

4

6

8

10

12

14

16

18

0 20 40 60 80 100 120 140 160

TIME

AVG

CN

TS/P

IXEL

LEFT LUNG POSTERIOR VIEW COUNTS

0

2

4

6

8

10

12

14

16

18

0.0 20.0 40.0 60.0 80.0 100.0 120.0 140.0 160.0

TIME (HOURS)

AVG

CN

TS/P

IXEL

RIGHT LUNG POSTERIOR VIEW COUNTS

0

2

4

6

8

10

12

14

16

18

0.0 20.0 40.0 60.0 80.0 100.0 120.0 140.0 160.0

TIME (HOURS)

AVG

CN

TS/P

IXEL

8 days 8 days post therapy post therapy dosedose

15 days15 dayspost therapy post therapy dosedose

As of October 17, 2007As of October 17, 2007

Both patients are doing very wellBoth patients are doing very wellNo recurrence of cancerous cellsNo recurrence of cancerous cells

AcknowledgmentsAcknowledgments

Stephanie Lee, M.D., Ph.D.Stephanie Lee, M.D., Ph.D.Dept. Endocrine / DiabetesDept. Endocrine / DiabetesBoston University Medical CenterBoston University Medical Center

Richard H. Behrman, Ph.D.Richard H. Behrman, Ph.D.Head Medical Physicist, Diagnostic RadiologyHead Medical Physicist, Diagnostic RadiologyBoston University Medical CenterBoston University Medical Center