CA Tiroides NCCN 2012

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Version 2.2012, 12/19/11 © National Comprehensive Cancer Network, Inc. 2011, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN®. ®

NCCN Guidelines IndexThyroid Table of Contents

Discussion

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) ®

Thyroid CarcinomaVersion 2.2012



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Discussion

NCCN Thyroid Carcinoma Panel Members

Summary of the Guidelines UpdatesNodule Evaluation (THYR-1)Principles of TSH Suppression (THYR-A)

FNA Results, Diagnostic Procedures, Primary Treatment (PAP-1)Incidental finding postlobectomy (PAP-2)

FNA Results, Diagnostic Procedures, Primary Treatment ( -1)

FNA Results, Diagnostic Procedures, Primary Treatment (MEDU-1)

Germline mutation of RET proto-oncogene (MEDU-3)

FNA Results, Diagnostic Procedures, Primary Treatment (ANAP-1)

Staging (ST-1)

HÜRT

Papillary Carcinoma

Follicular Carcinoma

Hürthle Cell Carcinoma

Medullary Thyroid Carcinoma

Anaplastic Carcinoma

FNA Results, Diagnostic Procedures, Primary Treatment (FOLL-1)

Medullary Thyroid Carcinoma Diagnosed After Initial Thyroid Surgery (MEDU-2)

Clinical Trials:

Categories of Evidence andConsensus:NCCN

All recommendationsare Category 2A unless otherwisespecified.

Thebelieves that the best managementfor any cancer patient is in a clinicaltrial. Participation in clinical trials isespecially encouraged.

NCCN

To find clinical trials online at NCCNmember institutions, click here:nccn.org/clinical_trials/physician.html

See NCCN Categories of Evidenceand Consensus

The NCCN Guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinicalcircumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCNGuidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein maynot be reproduced in any form without the express written permission of NCCN. ©2011.

®

NCCN Guidelines Version 2.2012 Table of ContentsThyroid Carcinoma

Printed by Esperanza Valentin on 5/21/2012 12:02:03 PM. For personal use only. Not approved for distribution. Copyright © 2012 National Comprehensive Cancer Network, Inc., All Rights Reserved.


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Discussion

Note: All recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

THYR-1

NCCN Guidelines Version 2.2012Thyroid Carcinoma – Nodule Evaluation

WORKUPCLINICAL PRESENTATION

aEvaluate and treat for hypothyroidism as clinically indicated.For nodules not meeting criteria for FNA, or nodules that appear to be benign by scan or FNA, surveillance should include repeat ultrasound

after 6-12 months; if stable for 1-2 years, then subsequent ultrasound can be considered at 3-5 year intervals.

b

Thyroid nodule(s)with low TSH

Radioiodineimaging

Cold or warm

Autonomouslyfunctioning (hot)

Evaluate and treat for thyrotoxicosis as indicated(malignancy is rare)b

Consider FNA based

on clinical andsonographic features

SeeSonographicFeatures(THYR-2)

b

For thyroid nodule known or suspected on exam or incidental imaging finding:

Measure thyroid stimulatinghormone (TSH)

Ultrasound of thyroid andcentral neckUltrasound of lateral neck(category 2B)

Thyroid nodule(s) withnormal or elevated TSHa


Printed by Esperanza Valentin on 5/21/2012 12:02:03 PM For personal use only Not approved for distribution Copyright © 2012 National Comprehensive Cancer Network Inc All Rights Reserved







Discussion


THYR-2

NCCN Guidelines Version 2.2012Thyroid Carcinoma – Nodule Evaluation

Solid noduleWith suspicious sonographic featuresWithout suspicious sonographic features

Mixed cystic-solid noduleWith suspicious sonographic featuresWithout suspicious sonographic features

Spongiform nodule

Simple cyst

Suspicious cervical lymph node

c

c

c

c

d

1.0 cm1.5 cm

1.5-2.0 cm2.0 cm

2.0 cm

Not indicatede

FNA node FNA associated thyroid nodule(s)±

Threshold for FNA

FNA, if indicated

or

Observeb

( )See THYR-3

SONOGRAPHIC FEATURES

The above criteria serve as general guidelines. In patients with high-risk clinical features, evaluations of nodules smaller than listed may be appropriate depending upon clinical concern. Allowance for informedpatient desires would include excisional biopsy (lobectomy or thyroidectomy) for definitive histology,especially in larger nodules (>4 cm) or higher risk clinical situations.

f

b

e

For nodules not meeting criteria for FNA, or nodules that appear to be benign by scan or FNA, surveillance should include repeat ultrasound after 6-12 months;if stable for 1-2 years, then subsequent ultrasound can be considered at 3-5 year intervals.

Aggregation of multiple microcystic components in more than 50% of the volume of the nodule.Except as therapeutic modality.

cSuspicious sonographic features: Hypoechoic, microcalcifications, increased central vascularity, infiltrative margins, taller than wide in transverse plane.

High-risk clinical features: radiation exposure as child or adolescent; first degree relative with thyroid cancer or MEN2; FDG avid on PET scan; personal history of

thyroid cancer-associated conditions such as familial adenomatous polyposis, Carney complex, Cowden syndrome; personal history of thyroid cancer in lobectomy.

d

f








http://nhl.pdf/





Discussion


NCCN Guidelines Version 2.2012Thyroid Carcinoma – TSH Suppression

THYR-A

PRINCIPLES OF THYROID STIMULATING HORMONE (TSH) SUPPRESSION

Because TSH is a trophic hormone that can stimulate the growth of cells derived from thyroidfollicular epithelium, the use of levothyroxine to maintain low TSH levels is considered optimalin treatment of patients with papillary, follicular, or Hürthle cell carcinoma. However, data arelacking to permit precise specification of the appropriate serum levels of TSH.

In general, patients with known residual carcinoma or at high risk for recurrence shouldhave TSH levels maintained below 0.1 mU/L, whereas disease-free patients at low risk for recurrence should have TSH levels maintained either slightly below or slightly above thelower limit of the reference range.

For low-risk patients with biochemical evidence but no structural evidence of disease(eg, Tg positive, but imaging negative), maintain TSH levels at 0.1 - 0.5 mU/L.

Patients who remain disease free for several years can probably have their TSH levelsmaintained within the reference range.

Given the potential toxicities associated with TSH-suppressive doses of levothyroxine---including cardiac tachyarrhythmias (especially in the elderly) and bone demineralization(particularly in post-menopausal women) as well as frank symptoms of thyrotoxicosis---therisk and benefit of TSH-suppressive therapy must be balanced for each individual patient.

Patients whose TSH levels are chronically suppressed should be counseled to ensureadequate daily intake of calcium (1200 mg/day) and vitamin D (1,000 units/day).

y p p y pp py g p , , g







Discussion


NCCN Guidelines Version 2.2012Thyroid Carcinoma – Papillary Carcinoma

PAP-2

Completion of thyroidectomy

Tumor 1-4 cm in diameter or Aggressive variantd

All of the following:

Negative margins

No contralateral lesionTumor < 1 cm in diameter No suspicious lymphnode

PRIMARY TREATMENT

Any of the following:

Tumor > 4 cmPositive marginsGross extra-thyroidal extensionMacroscopicmultifocal diseaseConfirmed nodalmetastasisVascular invasion

Papillarycarcinomafound post-lobectomy

Thyroid and neckultrasound, if notpreviously doneConsider chest x-ray, if notrecently done

Biopsy suspiciouslymph nodes or contralateral lesions

CLINICAL PRESENTATION

d

h

Tall cell variant, columnar cell, or poorly differentiated features.

Measurement of thyroglobulin and antithyroglobulin antibodies.

gSee Principles of TSH Suppression (THYR-A).

Observeh

Completion of thyroidectomy(category 2B)

or

Observeh

Consider

levothyroxinetherapy to keepTSH low or normalg

See

PostsurgicalEvaluation(PAP-3)

Suppress TSHwithlevothyroxine g

SeeSurveillanceandMaintenance(PAP-5)








Discussion



PAP-3

TSH + thyroglobulin(Tg) measurement+ antithyroglobulinantibodies ( -12 wk

postoperatively)

2

POSTSURGICAL EVALUATION

No grossresidualdiseasein neck

Gross residual

disease in neck

SuppressTSH withlevothyroxine g

Unresectable

Resectable Resect, if possible

No gross

residual disease

Gross residualdisease

Suspected

or proveninadequateRAI uptake

No imagingperformed

External-beam

radiationtherapy(EBRT)

RadioiodinetreatmentPost-treatment

I imagingConsider EBRT

131

SeePostsurgicalTherapy(PAP-4)

TSH + Tgmeasurement+ antithyroglobulinantibodies (2-12 wkpostoperatively)Total bodyradioiodine imaging

(category 2B)

AdequateRAI uptake

SeeSurveillanceand

Maintenance(PAP-5)

Not considering RAItherapy because of lack of clinical indication for RAI i,j

g

j

iSuspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.Clinical indications regarding radioactive iodine:

Radioactive iodine is recommended for all patients with gross extrathyroidal extension, primary tumor size greater than 4 cm, or distant metastases.Radioactive iodine is not routinely recommended for patients with either unifocal or multifocal papillary microcarcinomas (less than 1 cm) confined to the thyroid.Radioactive iodine is recommended for selected patients with primary tumors ranging from 1-4 cm confined to the thyroid, high risk histologies, vascular invasion, or cervical lymph node metastases when the combination of clinical factors predicts a significant risk of recurrence or disease specific mortality.

See Principles of TSH Suppression (THYR-A).

Consider radioiodine (RAI)therapy based on clinicalindications for RAI i,j








Discussion



PAP-4

Consider adjuvantradioiodine ablation(30-100 mCi)

post-treatment imaging

l todestroy residualthyroid function;

RadioiodinemCi

post-treatmentimaging or consider dosimetry for distant

metastasis

treatment(100-200 ) andl

POSTSURGICAL THERAPY

T4 (surgicallyresected grossextrathyroidalextension) andage > 45 y

All others

Consider EBRT

SeeSurveillanceandMaintenance(PAP-5)

2-12 wk post-thyroidectomy:No grossresidualdisease inneck

Suspected or proven radioiodineresponsiveresidual tumor

i

k

Suspected or proven thyroidbed uptake

i

Tg < 1 ng/mL withnegativeantithyroglobulinantibodies andradioiodineimaging negative

No radioiodinetreatment

g

i

k

l

Suspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.All patients should be examined, and palpable neck metastases or sonographically significantdisease should be surgically resected if possible before radioiodine treatment.The administered activity of RAI therapy should be adjusted for pediatric patients.


Total body

radioiodine imaging(category 2B) withadequate TSHstimulation (thyroidwithdrawal or recombinant humanTSH (rhTSH)stimulation)or

Clinical indicationfor radioiodinetherapy(category 2B)

i Suppress TSHwithlevothyroxine g







Discussion



PAP-6

TREATMENT OF METASTASES

CNS Consider neurosurgical resection adioiodine treatment withsteroid prophylaxis

q qand/or Image-guided EBRTIf radioiodine imaging positive, consider r

Bone

Surgical palliation, if symptomatic or asymptomaticin weight-bearing extremities

Radioiodine treatment, if radioiodine imaging positiveand/or withconsideration of dosimetry to maximize dosingand/or EBRTConsider bisphosphonate or denosumab therapyConsider embolization of metastases

r

s

t

For clinically progressive or symptomatic disease: clinical trialsfor non-radioiodine responsive tumors;consider small molecule kinase inhibitors or systemic therapy(if trial not available)

Sites other than CNS

Consider surgical resection and/or EBRT of selected, enlarging,or symptomatic metastasesand/or Radioiodine if positive uptake, with consideration of dosimetry to maximize dosingand/or For clinically progressive or symptomatic disease: clinicaltrials for non-radioiodine responsive tumors;consider small molecule kinase inhibitors or systemic therapy

(if trial not available)or Best Supportive Care

s

t

Metastatic diseaseContinue to suppressTSH with levothyroxine

g

g

t

q

r

s

For solitary lesions, either neurosurgical resection or stereotactic radiosurgery preferred.Denosumab can be associated with severe hypocalcemia; patients with hypoparathyroidism and vitamin D deficiency are at increased risk.Cytotoxic chemotherapy has shown to have minimal efficacy. Clinical trials investigating novel targeted therapies are ongoing.

While not FDA approved for treatment of thyroid cancer, commercially available small molecule kinase inhibitors (such as sorafenib, sunitinib, or pazopanib [category 2B

for pazopanib]) can be considered if clinical trials are not available or appropriate.

See Principles of TSH Suppression (THYR-A)

See Clinical trials available at the NCCN member institutions.

.










Discussion

NCCN Guidelines Version 2.2012Thyroid Carcinoma – Follicular Carcinoma

FOLL-1

Total thyroidectomy if invasive cancer, metastaticcancer, or patient preference

If lymph node(s) positive,perform therapeuticdissection of affectedcompartment:

c

Central neck dissection

(level VI)Lateral neck dissection(levels II, III, IV, and Vb,include levels I and Va if clinically involved).Consider preservation of the cervical sensory nerves

DIAGNOSTICPROCEDURES

PRIMARY TREATMENT

CT/MRI for fixed, bulky, or substernal lesionsEvaluate vocal cord mobilityConsider chest x-ray

b

Consider lateral neckultrasound

SeePostsurgicalEvaluation(FOLL-2)

Minimallyinvasivecancer d

Benign

Invasive cancer (extensive

vascular invasion)


or

Observe

Observe

Completion of

thyroidectomy

Follicular neoplasmor Follicular lesion of undeterminedsignificance

a

a

( )See THYR-3

Consider

levothyroxinetherapy tokeep TSH lowor normale

SeeSurveillanceand

Maintenance(FOLL-4)

Benign

Levothyroxinetherapy tokeep TSHnormale

Follicular carcinoma

FNARESULTS


d

e

Minimally invasive cancer is characterized as a well-defined tumor with microscopic capsular and/or a few foci of vascular invasion and often requiresexamination of at least 10 histologic sections to demonstrate.


b

c

Use of iodinated contrast will delay treatment with RAI, but may be required for fixed, bulky or substernal lesions.Ultrasound detected or clinically apparent disease.

aThe diagnosis of follicular carcinoma requires evidence of either vascular or capsular invasion, which cannot bedetermined by FNA. Molecular diagnostics may be usefulto allow reclassification of follicular lesions (follicular

neoplasm or follicular lesions of undetermined significance)as more likely to be benign or more likely to be malignant.If molecular testing suggests papillary thyroid carcinoma,see ( )PAP-1

Papillary carcinoma See PAP-3

or

Lobectomy/isthmusectomy

See PAP-2Papillary carcinoma







Discussion



FOLL-3

Suppress TSHwithlevothyroxine e

SeeSurveillanceandMaintenance(FOLL-4)

RadioiodinemCi

post-treatment imagingor consider dosimetryfor distant metastasis

treatment(100-200 ) andi


2-12 wkpost-thyroidectomy:No gross residualdisease in neck withadequate TSHstimulation(thyroid withdrawalor rhTSH stimulation)


f

h


f


Total body radioiodineimaging (category 2B) withadequate TSH stimulation(thyroid withdrawal or rhTSH stimulation)or Clinical indication for RAI

therapy (category 2B)g

e

f

h

i

Suspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.All patients should be examined, and palpable neck metastases or sonographically significant disease should be surgically resected if possible before radioiodinetreatment.

The administered activity of RAI therapy should be adjusted for pediatric patients.


Tg < 1 ng/mL withnegativeantithyroglobulinantibodies andradioiodineimaging negative


and post-treatmentimaging

i todestroy residualthyroid function







Discussion



FOLL-5


CNSConsider neurosurgical resectionn and/or Image-guided EBRTIf radioiodine imaging positive, consider radioiodine treatmentwith steroid prophylaxis

n

Bone

Surgical palliation, if symptomatic or asymptomatic in weight-bearing extremities

Radioiodine treatment, if radioiodine imaging positiveand/or withconsideration of dosimetry to maximize dosingand/or EBRTConsider bisphosphonate or denosumab therapyConsider embolization of metastases

o

p

q

For clinically progressive or symptomatic disease: clinical trials for

non-radioiodine responsive tumors; consider small moleculekinase inhibitor or systemic therapy (if trial not available)


Consider surgical resection and/or EBRT of selected, enlarging,or symptomatic metastasesand/or Radioiodine if positive uptake, with consideration of dosimetry to maximize dosingand/or For clinically progressive or symptomatic disease: clinicaltrials for non-radioiodine responsive tumors; consider small

molecule kinase inhibitor or systemic therapy (if trial not available)or Best Supportive Care

p

q

e

q

n

o

p

For solitary lesions, either neurosurgical resection or stereotactic radiosurgery preferred.Denosumab can be associated with severe hypocalcemia; patients with hypoparathyroidism and vitamin D deficiency are at increased riskCytotoxic chemotherapy has shown to have minimal efficacy. Clinical trials investigating novel targeted therapies are ongoing.

While not FDA approved for treatment of thyroid cancer, commercially available small molecule kinase inhibitors (such as sorafenib, sunitinib or pazopanib [category 2B

for pazopanib]) can be considered if clinical trials are not available or appropriate.

,


See Clinical trials available at the NCCN member institutions.

.

Metastatic diseaseContinue to suppress

TSH with levothyroxinee










Discussion


NCCN Guidelines Version 2.2012Thyroid Carcinoma – H rthle Cell Carcinomaü

H RT-1Ü

Hürthle cellneoplasma

( )See THYR-3

Total thyroidectomy, if invasivecancer or patient preference

If lymph node(s) positiveperform therapeuticdissection of affectedcompartment:

If node(s) negative, consider

prophylactic central neckdissection (category 2B)

c

d

Central neck dissection(level VI)

Lateral neck dissection(levels II, III, IV, and Vb,include levels I and Va if clinically involved).Consider preservation of thecervical sensory nerves


PRIMARY TREATMENT

CT/MRI for fixed, bulky, or substernal lesions

Consider chest x-ray

b

Evaluate vocal cord mobility

Consider lateral neckultrasound

Minimallyinvasivecancer f

Benign

Invasive cancer (extensivevascular invasion)


or

Observe

Observe


Consider levothyroxinetherapy tokeep TSH lowor normalg

SeeSurveillance

andMaintenance(H RT-4)Ü

See

PostsurgicalEvaluation(H RT-2)Ü

Benign

Levothyroxinetherapy tokeep TSH

normal

g

Hürthle cellcarcinomae

FNARESULTS

d

e

f

g

Possible benefit to reduce recurrence must be balanced with risk of hypoparathyroidism.Also known as oxyphilic, oncocytic, or follicular carcinoma, oncocytic type.Minimally invasive cancer is characterized as a well-defined tumor with microscopic capsular and/or a few foci of vascular invasion and often requires examination of at least 10 histologicsections to demonstrate.See Principles of TSH Suppression (THYR-A).

a

b

c

The diagnosis of Hürthle cell carcinoma requires evidenceof either vascular or capsular invasion, which cannot bedetermined by FNA.Use of iodinated contrast will delay treatment with RAI but,may be required for fixed, bulky or substernal lesions.Ultrasound detected or clinically apparent disease.

or

Lobectomy/isthmusectomy








Discussion



H RT-2Ü

POSTSURGICAL EVALUATION

Gross residualdisease in neck

SuppressTSH withlevothyroxine g

SeeSurveillanceandMaintenance(H RT-4)Ü

Unresectable

Resectable Resect, if possible

No grossresidual disease

Gross residualdisease

TSH + Tgmeasurement+ antithyroglobulinantibodies (2-12 wkpostoperatively)Total bodyradioiodine imaging

(category 2B)

EBRT

No scanperformed

RadioiodinetreatmentPost-treatment

I imagingConsider EBRT

131

No grossresidualdiseasein neck

Suspectedor proveninadequateRAI uptake

AdequateRAI uptake

TSH + Tgmeasurement+ antithyroglobulinantibodies (2-12 wkpostoperatively)

SeePostsurgicalTherapy(H RT-3)Ü

SeeSurveillanceandMaintenance(H RT-4)Ü

g

h

iSuspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.Clinical indications regarding radioactive iodine:Radioactive iodine is recommended for all patients with gross extrathyroidal extension, primary tumor size greater than 4 cm, any tumor size with vascular invasion, or distant metastases.Radioactive iodine is not required for minimally invasive follicular thyroid carcinoma or Hürthle cell carcinoma confined to the thyroid when the primary tumor is smalland demonstrates only invasion of the tumor capsule without vascular invasion.


Consider radioiodine (RAI)therapy based on clinicalindications for RAIh,i

Not considering RAI therapybecause of lack of clinicalindication for RAIh,i








Discussion



H RT-3Ü

See

SurveillanceandMaintenance(H RT-4)Ü

Suppress TSHwithlevothyroxine g

T4 (surgicallyresected grossextrathyroidalextension) andage > 45 y

All others

Consider EBRT

RadioiodinemCi

post-treatment imagingor consider dosimetryfor distant metastasis

treatment(100-200 ) andk


2-12 wk post-thyroidectomy:No gross residualdisease in neckwith adequate TSHstimulation (thyroidwithdrawal or rhTSH stimulation)


h

j


h


Total bodyradioiodineimaging(category 2B)with adequateTSHstimulation(thyroidwithdrawal or rhTSHstimulation)

or Clinicalindication for RAI therapy(category 2B)

i

g

h

j

k

Suspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.All patients should be examined, and palpable neck metastases or sonographically significant disease should be surgically resected if possible before radioiodinetreatment.

The administered activity of RAI therapy should be adjusted for pediatric patients.


Tg < 1 ng/mLwith negativeantithyroglobulinantibodies andradioiodineimaging negative


and post-treatment

imaging

k todestroy residualthyroid function






NCCN G id li V i 2 2012









Discussion



H RT-5Ü


CNSConsider neurosurgical resectionp and/or Image-guided EBRTIf radioiodine imaging positive, consider radioiodine treatmentwith steroid prophylaxis

p

Bone

Surgical resection, if symptomatic or asymptomatic

in weight-bearing extremitiesEBand/or RTConsider bisphosphonate or denosumab therapyConsider embolization of metastases

q

r For clinically progressive or symptomatic disease:clinical trials for non-radioiodine responsive tumors;consider small molecule kinase inhibitor or systemictherapy (if trial not available)

s


Consider surgical resection and/or EBRT of selected,enlarging, or symptomatic metastasesand/or Radioiodine if positive uptake, with considerationof dosimetry to maximize dosingand/or For clinically progressive or symptomaticdisease: clinical trials for non-radioiodine responsivetumors; consider small molecule kinase inhibitor or systemic therapy (if trial not available)or Best Supportive Care

r s

Metastatic diseaseContinue to suppress

TSH with levothyroxineg

g

p

q

r

s

For solitary lesions, either neurosurgical resection or stereotactic radiosurgery preferred.Denosumab can be associated with severe hypocalcemia; patients with hypoparathyroidism and vitamin D deficiency are at increased riskCytotoxic chemotherapy has shown to have minimal efficacy. Clinical trials investigating novel targeted therapies are ongoing.

While not FDA approved for treatment of thyroid cancer, commercially available small molecule kinase inhibitors (such as sorafenib, sunitinib, or pazopanib [category 2Bfor pazopanib]) can be considered if clinical trials are not available or appropriate.


See Clinical trials available at the NCCN member institutions

.

.









NCCN G id li I dNCCN G id li V i 2 2012



http://neuroendocrine.pdf/





Discussion


NCCN Guidelines Version 2.2012Thyroid Carcinoma – Medullary Carcinoma

MEDU-2

CLINICALPRESENTATION

ADDITIONAL WORKUP MANAGEMENT

Medullary thyroidcarcinomadiagnosed after initial thyroidsurgery

Germline RET mutation

Family history of MEN 2Basal serum calcitonin above the reference rangeCross sectional imaging (usually neck ultrasound)suspicious for residual tumor Histology evidence of C-cell hyperplasia,multifocality, extrathyroidal extension, or locoregional metastases

See Additional Workup

for Medullary thyroidcarcinoma on FNA(MEDU-1)

If none of these riskfactors are present

If any of these riskfactors are present

See Management 2-3Months Postoperative(MEDU-5)




NCCN Guidelines IndexNCCN Guidelines Version 2 2012










Discussion



MEDU-5

Basalcalcitonin

CEA

Detectablebasalcalcitonin

or ElevatedCEA

Basalcalcitoninundetectableor

CEA withinreferencerangeh

Neck imagingIf calcitonin

150 pg/mL,

cross sectionalimaging should

include contrast-enhanced CT or MRI of the neck,chest, abdomenwith liver protocol i

MANAGEMENT2-3 MONTHS

POSTOPERATIVE

SURVEILLANCE

Observe

Imagingpositive or symptomaticdisease

Imagingnegative andasymptomatic

Annual serum calcitonin, CEAConsider neck ultrasoundAdditional studies or morefrequent testing if significantlyrising calcitonin or CEANo additional imagingrequired if calcitonin and CEAstableFor MEN 2B or 2A, annualscreenings for pheochromocytoma andhyperparathyroidism (MEN 2A)

Continueobservationor Consider cervicalreoperation, if

primary surgeryincomplete

Continueobservation

Serum calcitonin, CEA

every 6-12 moAdditional studies or morefrequent testing based oncalcitonin/CEA doublingtimeNo additional imagingrequired if calcitonin andCEA stable

See Recurrent or Persistent Disease(MEDU-6)

Imagingpositive

Imagingnegative

Imagingpositive

Imagingnegative

h

iThe likelihood of significant residual disease with an undetectable basal calcitonin is very low.Bone scan and MRI of axial skeleton should be considered in patients with very elevated calcitonin levels.

See Recurrent or Persistent Disease(MEDU-6)

NCCN Guidelines IndexNCCN Guidelines Version 2 2012










Discussion



MEDU-6

Locoregional

Symptomatic,distant metastases

Asymptomatic,distant metastases

Surgical resection± postoperative EBRTor Consider EBRT or vandetanibfor unresectable symptomaticor progressive disease

j

Consider palliative resection,ablation (eg, radiofrequency[RFA], embolization, or other regional therapy), or other regional treatmentor Vandetanib j

Disseminatedsymptomaticdisease

Clinical trial (preferred)or EBRT for focal symptomsor Vandetanibor Consider other small molecule kinase inhibitorsor Dacarbazine (DTIC)-based chemotherapy

Consider bisphosphonate or denosumabtherapy for bone metastasesBest supportive care

j

l

k

RECURRENT OR PERSISTENT DISEASE

Observeor Consider resection (if possible),ablation (eg, RFA, embolization,or other regional therapy), or vandetanib if progressivedisease

j

j

l

Only health care professionals and pharmacies certified through the vandetanib Risk Evaluation and Mitigation Strategy (REMS) program, a restricted distributionprogram, will be able to prescribe and dispense the drug.While not FDA approved for treatment of thyroid cancer, other commercially available small molecule kinase inhibitors (such as sorafenib or sunitinib) can be consideredif clinical trials or vandetanib are not available or appropriate, or if the patient progresses on vandetanib.

Denosumab can be associated with severe hypocalcemia; patients with hypoparathyroidism and vitamin D deficiency are at increased risk.

k

NCCN Guidelines IndexNCCN Guidelines Version 2.2012









Thyroid Table of ContentsDiscussion


NCCN Guidelines Version 2.2012Thyroid Carcinoma – Anaplastic Carcinoma

ANAP-1

Anaplasticcarcinomaa

FNA OR COREBIOPSY FINDING


PRIMARY TREATMENT

CBCSerum calciumHead, neck, chest,abdomen, pelvis CTTSHConsider FDG-PET

± CT scanConsider bone scan

Locally resectable(rarelyencountered)

Unresectablelocal tumor

Total or near-total

thyroidectomySelective resection of involved local or regionalstructures and lymph nodes

Clinical trials preferred for persistent, locoregional, or

distant diseaseConsider EBRT(consider hyperfractionation)± radiosensitizingchemotherapyBest Supportive Care

aAn FNA diagnosis suspicious for anaplastic carcinoma should consider core biopsy.

Clinical trials preferred for

persistent, locoregional, or distant diseaseConsider EBRT(consider hyperfractionation)and/or chemotherapyBest supportive care






NCCN Guidelines Indexf C

NCCN Guidelines Version 2.2012 Staging








Thyroid Table of ContentsDiscussion

ST-2

Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCCCancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC (SBM). (For complete information and data supportingthe staging tables, v is it . )Any citat ion or quotation of this material must be credited to theAJCC as i ts primary source. The inclusion of thisinformation herein does not authorize any reuse or further distribution without the expressed, written permission of Springer SBM, on behalf of the AJCC.

www.springer.com

g gThyroid Carcinoma

Stage grouping:Separate stage groupings are recommended for papillaryor follicular (differentiated), medullary, and anaplastic(undifferentiated) carcinoma.

Papillary or Follicular (differentiated)

Papillary or Follicular

Medullary Carcinoma (all age groups)

Anaplastic Carcinoma

Under 45 YearsAny T Any N M0Any T Any N M1

45 Years and Older T1 N0 M0T2 N0 M0T3 N0 M0T1 N1a M0T2 N1a M0T3 N1a M0

T4a N0 M0T4a N1a M0T1 N1b M0T2 N1b M0T3 N1b M0

T4a N1b M0T4b Any N M0

Any T Any N M1

T1 N0 M0T2 N0 M0T3 N0 M0T1 N1a M0T2 N1a M0T3 N1a M0

T4a N0 M0T4a N1a M0T1 N1b M0T2 N1b M0T3 N1b M0

T4a N1b M0

T4b Any N M0

Any T Any N M1

All anaplastic carcinomas are considered Stage IVT4a Any N M0T4b Any N M0

Any T Any N M1

There are four major histopathologic types:

Stage IStage II

Stage IStage IIStage III

Stage IVA

Stage IVBStage IVC

Stage IStage II

Stage III

Stage IVA

Stage IVB

Stage IVC

Stage IVAStage IVBStage IVC

Histopathologic Type

Papillary carcinoma (including follicular variant of papillary carcinoma)Follicular carcinoma (including Hurthle cell carcinoma)Medullary carcinomaUndifferentiated (anaplastic) carcinoma




http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf

http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf





Discussion

NCCN Guidelines Version 2.2012Thyroid Carcinoma

A ti t ith l ti th id h d d bl l t






Version 2.2012, 12/19/11 © National Comprehensive Cancer Network, Inc. 2011, All rights reserved. The NCCN Guidelines® and this illustr ation may not be reproduced in any for m without the express written permission of NCCN®. MS-33

A patient with anaplastic thyroid cancer had a durable complete

response in a phase I trial with CA4P, and he has been disease free for

more than 3 years.335,336 Recent data using fosbretabulin, which is

another vascular disrupting agent, in 26 patients with advanced

anaplastic thyroid cancer showed that 33% of patients survived more

than 6 months.333

Multimodality therapy should also be considered.337-340 Although optimal

results have been reported with hyperfractionated external-beam RT

combined with chemotherapy, the panel acknowledged that

considerable toxicity is associated with such treatment and that

prolonged remission is uncommonly reported.341 A recent study found

that surgery and RT were associated with improved survival but not

chemotherapy.342 The guidelines do not recommend particular

chemotherapeutic agents, either for radiosensitization or full-dose

therapy, because of a lack of clear evidence of efficacy for any

particular regimen.


Discussion

NCCN Guidelines Version 2.2012Thyroid Carcinoma






Version 2.2012, 12/19/11 © National Comprehensive Cancer Network, Inc. 2011, All rights reserved. The NCCN Guidelines® and this illustr ation may not be reproduced in any for m without the express written permission of NCCN®. MS-34

Maximum Tumor Diameter (cm)Patients at Risk

P e r c e n t R e c u r r e n c e o r C a n c e r D e a t h

<1

30

25

20

15

10

5

0

1-1.9 2-2.9 3-3.9 4-4.9 5-5.9

106 281 320 174 98 135

RecurrenceR =0.672

Cancer DeathR =0.672

Age at DiagnosisPatients at Risk

E

v e n t s p e r D e c a d e ( % ) Recurrence

Cancer Death

0-9

60

50

40

30

20

10

0

10-19 20-29 30-39 40-49 50-59 60-69 70-91

11 95 440 363 224 118 60 40

Figure 1:

Relationship of cancer recurrence and mortality to patient age attime of diagnosis

(Reprinted and adapted from AM J Med, 97, Mazzaferri EL and

Jhiang SM, Long-term impact of initial surgical and medical therapy

on papillary and follicular thyroid cancer, pp 418-428, 1994, with

permission from Excerpta Medica Inc.).

Figure 2:

Relationship of cancer recurrence and mortality to tumor size

(Reprinted and adapted from AM J Med, 97, Mazzaferri EL and

Jhiang SM, Long-term impact of initial surgical and medical therapy

on papillary and follicular thyroid cancer, pp 418-428, 1994, with

permission from Excerpta Medica Inc.).


CA Tiroides NCCN 2012

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