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Management Guidelines for Patients Management Guidelines for Patients with Differentiated Thyroid Cancerwith Differentiated Thyroid Cancer

การประชุมวิชาการประจําปการประชุมวิชาการประจําป 1717 ตุลาคมตุลาคม 25502550““Humanized Health CareHumanized Health Care””

รศรศ..พญพญ..อัมพิกาอัมพิกา มังคละพฤกษมังคละพฤกษ

รศรศ..นพนพ..ธีรพรธีรพร รัตนาเอนกชยัรัตนาเอนกชยั รศรศ..นพนพ..จรูญศักดิ์จรูญศักดิ์ สมบูรณพรสมบูรณพร

Management of DTCManagement of DTC

SurgerySurgeryRadioiodine treatmentRadioiodine treatmentThyroid hormone suppressive therapyThyroid hormone suppressive therapyLifeLife--long followlong follow--upup


SurgerySurgeryRadioiodine treatmentRadioiodine treatment

Initial therapyInitial therapy

Thyroid hormone suppressive therapyThyroid hormone suppressive therapyLifeLife--long followlong follow--upup


SurgerySurgeryRadioiodine treatment Radioiodine treatment

Initial therapyInitial therapy

Thyroid hormone suppressive therapyThyroid hormone suppressive therapyLifeLife--long followlong follow--upup

Management Guidelines for Patients Management Guidelines for Patients with Differentiated Thyroid Cancerwith Differentiated Thyroid Cancer

PostsurgicalPostsurgical Treatment:Treatment:

““Role of Radioiodine Ablation of Role of Radioiodine Ablation of Thyroid Remnant and Thyroid Remnant and

Treatment of Distant MetastasisTreatment of Distant Metastasis””

To remove the primary tumor, disease that To remove the primary tumor, disease that has extended beyond the thyroid capsule, has extended beyond the thyroid capsule, and involved cervical lymph nodesand involved cervical lymph nodes

Completeness of surgical resection = determinant of Completeness of surgical resection = determinant of outcomeoutcomeResidual Residual metastaticmetastatic lymph nodes = most common lymph nodes = most common site of disease recurrencesite of disease recurrence

The importance of surgeryThe importance of surgery

What is the role of postoperative What is the role of postoperative radioiodine remnant ablation?radioiodine remnant ablation?

To destroy residual thyroid tissueTo destroy residual thyroid tissueDecrease the risk for recurrent Decrease the risk for recurrent locoloco--regional diseaseregional diseaseFacilitate longFacilitate long--term surveillance with term surveillance with whole body scan (WBS) and/or stimulated whole body scan (WBS) and/or stimulated thyroglobulinthyroglobulin ((TgTg) measurements) measurements

Goal of remnant ablationGoal of remnant ablation

Does postDoes post--surgical radioiodine surgical radioiodine ablation ablation decreasedecrease cancer cancer recurrencerecurrence

and and mortalitymortality rates ?rates ?

Meta-analysis of radioiodine effectiveness(Sawka et al. JCEM 2004)

SeriesSeries NN FollowFollow--UpUp(yr)(yr)

II--131 Effectiveness131 EffectivenessCancer MortalityCancer Mortality

II--131 Effectiveness131 EffectivenessCancer RecurrenceCancer Recurrence

Ohio StateOhio State 15101510 16.616.6 P<0.0001P<0.0001 P<0.016P<0.016UCSFUCSF 187187 10.610.6 NSNS P<0.0001P<0.0001Hong KongHong Kong 587587 9.29.2 NSNSTorontoToronto 382382 10.810.8 NSNSIIIinoisIIIinois RegReg 22822282 6.56.5 NSNSGundersenGundersen 177177 7.27.2 NSNSMD AndersonMD Anderson 15991599 1111 P<0.001P<0.001VillejuifVillejuif 273273 7.37.3 NSNSMexicoMexico 229229 55 NSNSPisaPisa 964964 1212 NSNS P<0.001P<0.001Mayo ClinicMayo Clinic 24442444 >25>25 NSNS NSNS

To which patients should thyroid ablation be offered?To which patients should thyroid ablation be offered?

To which patients should thyroid ablation be offered?To which patients should thyroid ablation be offered?European ConsensusEuropean Consensus ((PaciniPacini et al. EJE 2006)et al. EJE 2006)

To which patients should thyroid ablation be offered?To which patients should thyroid ablation be offered?European ConsensusEuropean Consensus ((PaciniPacini et al. EJE 2006)et al. EJE 2006)

BenefitBenefitVery lowVery low--risk patients:risk patients:UnifocalUnifocal T1 T1 ≤≤1 cm N0 M01 cm N0 M0 No evidenceNo evidence

LowLow--risk patients:risk patients:T1>1 cm N0 M0T1>1 cm N0 M0 May decrease recurrenceMay decrease recurrenceT2 N0 M0T2 N0 M0 but evidence not definitivebut evidence not definitive

HighHigh--risk patients:risk patients:any T3 and T4any T3 and T4 Evidence of decreasedEvidence of decreasedany T N1any T N1 recurrence and mortality raterecurrence and mortality rateM1M1

Recommendation for remnant ablationRecommendation for remnant ablation

Management guidelines for patients with thyroid nodules and differentiated thyroid cancer.The American Thyroid Association Guideline Taskforce. Thyroid, Vol 16, No 2, 2006

According to American Joint Committee on Cancer (AJCC) According to American Joint Committee on Cancer (AJCC) 66thth edition (2002)edition (2002)

All patients with stage IVAll patients with stage IVAll patients with stage IIIAll patients with stage IIIAll patients with stage II and < age 45,All patients with stage II and < age 45,Most patients with stage II and Most patients with stage II and >> 45 years45 yearsSelected patients with stage ISelected patients with stage I

MultifocalMultifocal diseasediseaseNodal metastasesNodal metastasesExtrathyroidExtrathyroid or vascular invasionor vascular invasionMore aggressive More aggressive histologieshistologies

Recommendation for remnant ablationRecommendation for remnant ablation


Does postDoes post--surgical radioiodine ablation surgical radioiodine ablation improve the followimprove the follow--up procedureup procedure with serum with serum thyroglobulinthyroglobulin and Iand I--131 whole body scan ?131 whole body scan ?

““TgTg is produced only by the thyroid.is produced only by the thyroid.””

II--131 ablation facilitates follow131 ablation facilitates follow--up proceduresup procedures

Ablation of thyroid remnant renders the Ablation of thyroid remnant renders the patients patients TgTg--free.free.

In this case, any detectable level of serum In this case, any detectable level of serum TgTgthereafter is due to recurrent disease.thereafter is due to recurrent disease.

II--131 ablation facilitates follow131 ablation facilitates follow--up procedures.up procedures.

Large remnant in the Large remnant in the neck may mask the neck may mask the visualization of visualization of cervical LN cervical LN metastasis at WBSmetastasis at WBS

Is there a need for diagnostic IIs there a need for diagnostic I--131 WBS 131 WBS before ablation?before ablation?


0

20

40

60

80

30 (n=536) 100 (n=178) 30 (n=197)

ABLATED

NOT ABLATED

Preceded by 1 mCi tracer dose No tracer dose

I-131 (mCi)

%

Success rate

Bianchi F et al. Thyroid 2005


0

20

40

60

80

30 (n=536) 100 (n=178) 30 (n=197)

ABLATED

NOT ABLATED


I-131 (mCi)

%

Success rate


So predictable


0

20

40

60

80

30 (n=536) 100 (n=178) 30 (n=197)

ABLATED

NOT ABLATED


I-131 (mCi)

%

Success rate


Stunning effect

So predictable

Why so predictable ? Why so predictable ?

1. Berry1. Berry’’s ligament (connecting posterior s ligament (connecting posterior surface of thyroid to trachea)surface of thyroid to trachea)

2. Recurrent laryngeal nerve 2. Recurrent laryngeal nerve (entering larynx)(entering larynx)

Total Total thyroidectomythyroidectomy rarely removes rarely removes all thyroid tissue. all thyroid tissue.

“More than 99.5% of total thyroidectomy cases have residual thyroid remnant.”

Thyroid stunning effectThyroid stunning effect

Fact or Fiction ?Fact or Fiction ?

StunningStunningDecreased ability (of normal thyroid or Decreased ability (of normal thyroid or metastaticmetastatictissue) to trap or retain therapeutic Itissue) to trap or retain therapeutic I--131131 as a as a result of previously administered diagnostic result of previously administered diagnostic activitiesactivities

First report by Rawson,1961First report by Rawson,1961

If that ability recovers to its initial level, the effect If that ability recovers to its initial level, the effect is is transienttransient and can be called and can be called ““stunningstunning””

It is not know at what time following administration It is not know at what time following administration it it appearsappears, nor , nor how long it lastshow long it lasts

StunningStunning

15 Aug Dx-WBS, 72 hrs after

5 mCi I-131

25 Aug Rx-WBS, 72 hrs after

150 mCi I-131

10 October Rx-WBS, 72 hrs

after 150 mCi I-131

Postoperative WBSPostoperative WBSEU EU

““This procedure may be avoided without loss of This procedure may be avoided without loss of information.information.””May be performed in cases of uncertainty of the May be performed in cases of uncertainty of the extent of extent of thyroidectomythyroidectomy..

USUS““There is increasing trend to avoid There is increasing trend to avoid pretherapypretherapy scan..scan..””May be useful in evaluating extent of May be useful in evaluating extent of thyroidectomythyroidectomyand in making decision regarding the treatment and and in making decision regarding the treatment and the dose of Ithe dose of I--131.131.

Remnant ablationRemnant ablation

Aim:Aim: Maximize I-131 uptake by thyroidtissue (serum TSH > 30 microIU/ml)

4 4 -- 6 weeks after the operation6 weeks after the operationRecombinant humanRecombinant human--TSH injectionTSH injection

Duration after thyroidectomy to raise

serum TSH > 30 microIU/ml

SeriesSeries YrYr NN 2 weeks

3 weeks

Sanchez R 2002 42 74% 95%Grigsby PW 2004 176 89% 90%US Guidelines 2006 At least 3 wk (90%)EU Guidelines 2006 4 - 5 wk

Protocol for Protocol for rhrh--TSH stimulated TSH stimulated remnant ablationremnant ablation

EMEA approval for ablation with 100 mCi I-131 in low-risk patients.

Which is the best activity of IWhich is the best activity of I--131 131 to be administered?to be administered?

Guidelines SNMGuidelines SNM

Nuclear Medicine ProcedureGuidelines for therapy of thyroid disease with iodine-131 version 1.0

Thyroid ablation:2.75 - 5.5 GBq (74 – 148 mCi)

Thyroid cancer in the neck or mediastinal lymph nodes:

5.55 - 7.4 GBq (148 – 200 mCi)

Treatment of distant metastases:> 7.4 GBq (> 200 mCi)


Patients successfully treatedPatients successfully treated (%)(%)StudyStudy 30 30 mCimCi 50 50 mCimCi 100 100 mCimCi

Creutzig,1987Creutzig,1987 50%50% No studiedNo studied 60%60%

Johansen, 1991Johansen, 1991 58%58% No studiedNo studied 52%52%

Bal, 1996Bal, 1996 63%63% 78%78% 74%74%SirisalipochSirisalipoch, 2004, 2004 No studiedNo studied 65%65% 89%89%

Bal, 2004Bal, 2004 83%83% 82%82% No studiedNo studied

Bianchi, 2005Bianchi, 2005 80%80% No studiedNo studied No studiedNo studied

TotalTotal 71%71% 75%75% 77%77%

Dose of IDose of I--131 remnant ablation: 131 remnant ablation: MetaMeta--analysisanalysis ((DoiDoi SASA et al, et al, ClinClin Med Med ResRes 2007)2007)

1. Minimum activity (301. Minimum activity (30--100 100 mCimCi) in low risk ) in low risk patient patient

There is a trend toward higher success rates with There is a trend toward higher success rates with higher activities.higher activities.

2. Higher activity (1002. Higher activity (100--200 200 mCimCi) if) ifResidual microscopic disease is suspected or Residual microscopic disease is suspected or documented.documented.There is more aggressive histology There is more aggressive histology egeg. tall cell, . tall cell, insular, columnar cell carcinomainsular, columnar cell carcinoma

Dose of IDose of I--131 remnant ablation131 remnant ablation


ContraindicationsContraindications

PregnantPregnantBreast feedingBreast feeding

Radioiodine (IRadioiodine (I--131)131)

Thyroid remnant and cervical LN Thyroid remnant and cervical LN metastasesmetastases

Thyroid remnantsThyroid remnants

MediastinalMediastinal LN and Lung metastasesLN and Lung metastases

Bone metastasesBone metastases

Additional Additional metastaticmetastatic foci found in 10 foci found in 10 --26% of patients.26% of patients.Most of them are in the neck, lungs and Most of them are in the neck, lungs and mediastinummediastinum..They altered disease stage in 10% and They altered disease stage in 10% and affect clinical management in 9affect clinical management in 9--15% of 15% of patients.patients.

PostPost--treatment WBStreatment WBS

Higher sensitivity of postHigher sensitivity of post--treatment WBStreatment WBS

Pre-treatment WBS Post-treatment WBS

Timing for postTiming for post--treatment WBStreatment WBS

EUEU33--5 days after I5 days after I--131 treatment131 treatment

USUSTypically at 5Typically at 5--8 days after treatment, 8 days after treatment, ““although published data supporting this time although published data supporting this time interval is lackinginterval is lacking..””

What is the role of radioiodine What is the role of radioiodine for distant metastasis ?for distant metastasis ?

Distant metastasesDistant metastases

Distant metastases occur in < 10% of thyroid Distant metastases occur in < 10% of thyroid cancer patients.cancer patients.Only retrospective studies areOnly retrospective studies are available on available on limited number of patients.limited number of patients.Only 30% may achieve CR with minor Only 30% may achieve CR with minor morbidity.morbidity.

Distant metastases :Distant metastases :Therapeutic toolsTherapeutic tools

Local treatmentsLocal treatments-- surgerysurgery-- external radiation beam therapyexternal radiation beam therapy-- embolizationembolization, cement injection, cement injection……II--131131LL--ThyroxineThyroxine

Distant metastases: Distant metastases: Therapeutic toolsTherapeutic tools

LL--ThyroxineThyroxineLocal treatment:Local treatment:-- surgerysurgery-- external radiation beam therapyexternal radiation beam therapy-- embolizationembolization, cement injection, cement injection……II--131 treatment131 treatmentSystemic treatmentSystemic treatment e.g. chemotherapye.g. chemotherapy

Guidelines SNMGuidelines SNM

Nuclear Medicine ProcedureGuidelines for therapy of thyroid disease with iodine-131 version 1.0

Thyroid ablation:2.75 - 5.5 GBq (74 – 148 mCi)

Thyroid cancer in the neck or mediastinal lymph nodes:

5.55 - 7.4 GBq (148 – 200 mCi)

Treatment of distant metastases:> 7.4 GBq (> 200 mCi)

II--131 and metastases131 and metastases

When should IWhen should I--131 treatment be stopped?131 treatment be stopped?

Absence of detectable disease as Absence of detectable disease as a function of the cumulative activitya function of the cumulative activity

48%

84%

96% 100%

0

20

40

60

80

100

0-200 201-400 401-600 >600

mCi

• Most absences of detectable disease are obtained with a cumulative activity of 600mCi or less.

• Administration of larger activities on an individual basis

Potential hazards of IPotential hazards of I--131131

•• Retrospective analysis of Retrospective analysis of 6841 patients treated with 6841 patients treated with 131131I.I.

•• Increased risk of solid Increased risk of solid tumors and tumors and leukemiasleukemiaswith increasing with increasing cumulative activity of cumulative activity of 131131II

•• The risk is significant for The risk is significant for > 22 > 22 GBqGBq (600mCi)(600mCi)

Evidence-Based MedicineEvidence-Based Medicine

Evidence-Based MedicineEvidence-Based Medicine

Best Evidence

Strength of panelistsStrength of panelists’’ recommendations based recommendations based on available evidenceon available evidence

AA Strongly recommends (good evidence)Strongly recommends (good evidence)BB Recommends (fair evidence)Recommends (fair evidence)CC Recommends (expert opinion)Recommends (expert opinion)

DD Recommends against (expert opinion)Recommends against (expert opinion)EE Recommends against (fair evidence)Recommends against (fair evidence)F F Strongly recommends against (good evidence)Strongly recommends against (good evidence)

I I Recommends neither for nor against (insufficient Recommends neither for nor against (insufficient evidence)evidence)

Thyroid Cancer GuidelinesThyroid Cancer Guidelines


Evidence based medicineEvidence based medicine

Best Evidence

Clinical Expertise Patient Preference

T h a n k Y o u

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