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NCCN Clinical Practice Guidelines in Oncology™

Thyroid

Carcinoma

V.2.2007

www.nccn.org



Version 2.2007, 04/20/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

NCCN® Practice Guidelines

in Oncology – v.2.2007

Guidelines IndexThyroid Carcinoma TOC

Staging, MS, References

NCCN Thyroid Carcinoma Panel Members

Steven I. Sherman, MD/Chair The University of Texas M. D. AndersonCancer Center

Peter Angelos, MD, PhDRobert H. Lurie Comprehensive Cancer Center of Northwestern University

Douglas W. Ball, MDThe Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins

David Byrd, MDFred Hutchinson Cancer ResearchCenter/Seattle Cancer Care Alliance

Orlo H. Clark, MDUCSF Comprehensive Cancer Center

Gilbert H. Daniels, MDDana-Farber/Brigham and Women’sCancer Center | Massachusetts GeneralHospital Cancer Center

Raza A. Dilawari, MD

St. Jude Children's ResearchHospital/Univeristy of TennesseeCancer Institute

Hormoz Ehya, MDFox Chase Cancer Center

ð

¶

†

¶

¶

ð

¶

¹

William B. Farrar, MDArthur G. James Cancer Hospital andRichard J. Solove Research Institute atThe Ohio State University

Robert F. Gagel, MDThe University of Texas M. D. Anderson

Cancer Center

Fouad Kandeel, MDCity of Hope

Richard T. Kloos, MDArthur G. James Cancer Hospital &Richard J. Solove Research Institute atThe Ohio State University

Peter Kopp, MDRobert H. Lurie Comprehensive Cancer Center of Northwestern University

Dominick M. Lamonica, MDRoswell Park Cancer Institute

Thom R. Loree, MD

Roswell Park Cancer Institute

William M. Lydiatt, MDUNMC Eppley Cancer Center at TheNebraska Medical Center

¶

ð Þ

ð

ð

ð

Þ

¶

¶

f

f

Judith McCaffrey, MDH. Lee Moffitt Cancer Center andResearch Institute at the University of South Florida

John A. Olson, Jr., MD, PhDDuke Comprehensive Cancer Center

John A. Ridge, MD, PhDFox Chase Cancer Center

Jatin P. Shah, MDMemorial Sloan-Kettering Cancer Center

James C. Sisson, MD

University of Michigan ComprehensiveCancer Center

R. Michael Tuttle, MDMemorial Sloan-Kettering Cancer Center

Marshall M. Urist, MD

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f

University of Alabama at Birmingham

Comprehensive Cancer Center

¶

¶

¶

Þ

ð

¶

*

ð Endocrinology

Pathology

Nuclear MedicineOtolaryngology

¶ Surgery/Surgical oncology

Þ Internal medicine

*Writing Committee Member

† Medical Oncology

¹

f

z

Continue

Thyroid Carcinoma

http://contents.pdf/









Table of Contents

Papillary Carcinoma

Medullary Carcinoma

NCCN Thyroid Carcinoma Panel MembersNodule Evaluation (THYR-1)

Follicular Carcinoma (FOLL-1)

Hürthle Cell Carcinoma ( -1)

Diagnosed by FNA (MEDU-1)

Germline mutation of RET proto-oncogene (MEDU-2)

Anaplastic Carcinoma (ANAP-1)

Guidelines Index

Print the Thyroid Carcinoma Guideline

·

·

·

·

FNA positive (PAP-1)

Incidental finding postlobectomy (PAP-2)

HÜRT

These guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinicianseeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances todetermine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kindwhatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines arecopyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced inany form without the express written permission of NCCN. ©2007.

For help using thesedocuments, please click here

Staging

Manuscript

References

Clinical Trials:

Categories of Consensus:NCCN All recommendations are Category2A unless otherwise specified.

See

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

NCCN Categories of Consensus

Summary of Guidelines Updates

Thyroid Carcinoma



http://print/

http://help.pdf/

http://help.pdf/

http://www.nccn.org/clinical_trials/physician.html





http://help.pdf/


http://print/








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.

Thyroid Carcinoma

Nodule Evaluation

WORKUPCLINICAL PRESENTATION

Clinically euthyroid:··

··

TSH measurementUltrasound of thyroid

and neck includingadjacent cervical lymphnodesFNA of noduleFNA of clinicallysuspicious lymphnodes

Follow-up as clinically indicated(Observe for criteria of increasedsuspicion - see above pathway)

Thyroidnodule with

unknownTSH

Nodules < 1 cm in diameter without enlarged cervicallymph nodes or suspicious findings by ultrasoundor nodules 1-4 cm with no suspicious criteria

·

·

Solitary nodule > 1 cm in diameter

Increased suspicion if anyof the following are present:

Age < 15 y or > 45 yMale sexNodule > 4 cm in diameter History of radiation exposureHistory of diseases associated with

thyroid cancer:HyperparathyroidismGardner’s syndromeFamilial adenomatous polyposisCarney complexCowden’s syndrome

Suspicious criteria by ultrasoundCentral hypervascularity

MicrocalcificationIncidentally identified focal PETpositive lesion in the thyroid

a

>

>

>

>

>

7

7

7

7

7

7

>

7

77

>

Pheochromocytoma

Irregular border

· Highly suspicious:Rapid nodule growth

b

>

>

>

>

>

>

>

Very firm noduleFixation to adjacentstructuresFamily history of thyroidcancer

Vocal cord paralysisEnlarged regional lymphnodesSymptoms of invasion intoneck structures

See FNAResults(THYR-2)

a

b

In selected cases, it may be reasonable to follow with serial ultrasounds.

Consider surgery after FNA.

Papillary carcinoma,finding postlobectomyfor benign disease

See Primary Treatment (PAP-2)

THYR-1

Thyroidnodule withlow TSH

See Primary Treatment (THYR-2)











c

d

e

This includes cytology suspicious for papillary carcinoma.If suspicious, perform serum calcitonin and CEA.

Consider trial of thyroxine therapy for small, clinically nonsuspicious, follicular neoplasm in a young female patient (category 3).

FNA RESULTS TREATMENT

Carcinoma

See pathway for carcinoma, above

Follicular neoplasm(suspicious/atypia)or presenting nodule

with low TSH

Benign(Hürthle cells in theabsence of neoplasm)

Insufficient

biopsy

Surgery e

·

·

ObserveIf nodule growth, repeat FNA or consider surgery

Repeat FNA, consider ultrasoundguidance and immediate cytologic reviewor consider surgery

Papillary c

Hürthle cell


See Primary Treatment (FOLL-1)

See Primary Treatment (HÜRT-1)

See Primary Treatment (MEDU-1)

See Primary Treatment (ANAP-1)Anaplastic

Hot

Cold Surgery

Thyroidscan

Follicular

Medullaryd

TSH high or normal

TSH lowEvaluate and treat for thyrotoxicosis as indicated(malignancy is rare)

Thyroidlymphoma See NCCN Non-Hodgkin’s Lymphoma Guideline

Back to ThyroidCarcinoma Table

of Contents

THYR-2

Pathology and

cytopathology slidesshould be reviewed at thetreating institution by apathologist with expertisein thyroid carcinoma.

Thyroid Carcinoma

Nodule Evaluation


Well-differentiated

Poorly-differentiated


http://nhl.pdf/

http://nhl.pdf/










Thyroid Carcinoma

Papillary Carcinoma

PapillarycarcinomaFNApositive

·

·

·

·

·

Consider chest x-

rayThyroidultrasound, if notpreviously doneConsider lateralneck ultrasound(category 2B)CT/MRI for fixed or substernal lesions

(avoid iodinatedcontrast, unlessessential)Evaluate vocalcord mobility(category 2B)

Indications for totalthyroidectomy:(any present)

Ag

·····

··

·

Age < 15 y or > 45 yRadiation historyKnown distant metastasesBilateral nodularityExtrathyroidal extension

Tumor > 4 cm in diameter Cervical lymph nodemetastases

gressive variant

a

b

Indications for totalthyroidectomy

lobectomy:(all present)

or

····

·

··

Age 15 y - 45 yNo prior radiationNo distant metastasesNo cervical lymph nodemetastasesNo extrathyroidalextension

Tumor < 4 cm in diameter No aggressive variant

a

b

PREOPERATIVE ORINTRAOPERATIVEDECISION-MAKING CRITERIA

DIAGNOSTICPROCEDURES

FNAFINDING

Total thyroidectomyIf lymph node(s) palpable or biopsypositive:··

Central neck dissection (level VI)Lateral neck dissection (levels II-V,sparing spinal accessory nerve,internal jugular vein, and

sternocleidomastoid muscle)Consider preservation of the cervicalsensory nerves, when feasible

Totalthyroidectomy(most common)(category 2B)

or

Lobectomy +isthmusectomy(category 2B)

PRIMARY TREATMENT

··

·

·

·

Aggressive variantMacroscopic multifocaldiseasePositive isthmusmarginsCervical lymph nodemetastasesExtrathyroidal extension

b

·

·

NegativemarginsNo contralaterallesion

See PostsurgicalEvaluation (PAP-3)

See PostsurgicalEvaluation (PAP-3)

a

b

Age is an approximation and not an absolute determination.

Tall cell, columnar cell, insular, oxyphilic, or poorly differentiated features.

Completion of thyroidectomy

·

·

Consider thyroglobulinmeasurementSuppress TSHwith thyroxine

See Surveillanceand Maintenance(PAP-5)

PAP-1












·

··

·

Clinically suspiciouslymph node,contralateral lesion,or pAggressive variantMacroscopicmultifocal disease

1 cm in diameter

erithyroidal nodeb

³

····

Negative marginsNo contralateral lesion< 1 cm in diameter No suspicious lymphnode

PRIMARY TREATMENT

···

> 4 cmPositive marginsExtra-thyroidalinvasion (T3 or T4)

Papillarycarcinomafound post-lobectomy for benign disease

·

·

Thyroid and neckultrasound, if notpreviously doneChest x-ray, if notrecently done

CLINICAL PRESENTATION

See PostsurgicalEvaluation(PAP-3)

PAP-2

bTall cell, columnar cell, insular, oxyphilic, or poorly differentiated features.

Thyroid Carcinoma

Papillary Carcinoma

Consider thyroglobulinmeasurement +antithyroglobulinantibodies

Completion of thyroidectomy (category 2B)

or

Thyroglobulin measurement+ antithyroglobulinantibodies

Consider thyroxinetherapy to keepTSH low/normal


See PostsurgicalEvaluation(PAP-3)

Thyroxine therapyto keep TSHlow/normal












TSH + thyroglobulinmeasurement +

antithyroglobulinantibodies (1-12 wkpostoperatively)

POSTSURGICAL EVALUATIONAFTER THYROIDECTOMY

No grossresidualdisease

in neck

Grossresidualdiseasein neck

SuppressTSH withthyroxine

SeeSurveillanceand

Maintenance(PAP-5)

Unresectable

Resectable Resect, if possible

No grossresidual disease

Gross residualdisease

Inadequateuptake

No scanperformed

RT

·

·

·

Radioiodinetreatment

Post-treatment

I scanRT

131

SeePostsurgicalTherapy(PAP-4)

·

·

TSH + thyroglobulinmeasurement +antithyroglobulinantibodies (1-12 wkpostoperatively)

Total bodyradioiodine scan(category 2B)

PAP-3

Adequateuptake

Thyroid Carcinoma

Papillary Carcinoma

·

·

·

·

< 1 cm confined toglandNo nodal metastasesNo distant metastasesNon-aggressivehistology

SeeSurveillanceandMaintenance(PAP-5)

·

·

·

·

1 cmor Nodal metastasesor Distant metastasesor Aggressive histology

³













Adjuvant radioiodineablation (30-100 mCi)of thyroid bed(category 2B) andposttreatment scan

RadioiodinemCi

posttreatment scan

treatment(100-200 ) and

Suppress

TSH withthyroxine

POSTSURGICAL THERAPY

T4 (surgicallyevident extra-

thyroidalinvasion) andage > 45 y

All others

Consider RT

SeeSurveillance

andMaintenance(PAP-5)

1-12 wkpostthyroidectomy:No gross residualdisease in neckwith adequate TSHstimulation (thyroidwithdrawal or recombinant rhTSH

stimulation)

Suspected or provenradioiodine avidresidual tumor

c

d

Suspected or proven thyroidbed uptake

c

Thyroglobulin< 1 ng/mL andradioiodinescan negative

No radioiodinetreatment

c

dSuspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.

All patients should be examined and palpable neck disease should be surgically resected before radioiodine treatment.

PAP-4

Thyroid Carcinoma

Papillary Carcinoma

Total bodyradioiodinescan(category 2B)

G id li I d













·

·

·

·

·

Physical examination, TSH and thyroglobulinmeasurement + antithyroglobulin antibodies at6 and 12 mo, then annually if disease-free

Consider additional nonradioiodine imaging(eg, FDG PET ± CT if Tg 10 ng/mL), if Iscans negative and stimulated Tg > 2-5 ng/mL

Periodic neck ultrasound

TSH stimulated thyroglobulin without

radioiodine scan at 12 mo in patientspreviously treated with RAI with recentnegative neck ultrasound and undetectableTSH suppressed thyroglobulin (anti-thyroglobulin antibody negative) and T1-2, N0-1, M0 at initial staging

If detectable thyroglobulin, distant metastasesor soft tissue invasion on initial staging,radioiodine scan every 12 mo until noradioactive iodine avid tumor is evident (either withdrawal of thyroid hormone or rhTSH)e

131³

SURVEILLANCE AND MAINTENANCE

Locoregional recurrence

Metastatic disease

·

·

Thyroglobulin > 10 ng mLthyroid hormone)

Scans (including PET)negative

/(off

Consider therapywith 100-150 mCi, posttreatment

I scan (category 3)

radioiodine

131

Surgery (preferred) if resectable

and/or Radioiodine treatment,if radioiodine scan positiveand/or RT, if radioiodine scan negative

See Treatment of Metastases(PAP-6)

RECURRENT DISEASE

eIf there is a high likelihood of therapy, thyroid hormone withdrawal suggested; if not, suggest using rhTSH.

PAP-5

Thyroid Carcinoma

Papillary Carcinoma

·

·

·

Stimulated Tg 1-10 ng/mLNon-resectable tumorsNon-radioiodine avid

Suppress TSH with thyroxine

Guidelines Index













TREATMENT OF METASTASES

Solitary CNS

Consider neurosurgical resection

Radioiodine treatment with rhTSH and steroidprophylaxis, if radioiodine scan positive

RT

and/or

and/or

Bone

·

·

·

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

Radioiodine treatment, if radioiodine scan positiveand/or

and/or RTConsider bisphosphonate therapyConsider embolization of metastases

Other

extracervical sites

Consider surgical resection of selected, enlarging,or symptomatic metastasesand/or Radioiodine if positive uptake, with considerationof dosimetry to maximize dosingand/or Clinical trials for non-radioiodine avid tumors ;systemic therapy if not in clinical trialor Best Supportive Care

f

Metastatic disease· Continue to suppress

TSH with thyroxine

PAP-6

Thyroid Carcinoma

Papillary Carcinoma

f Cytotoxic chemotherapy has shown to have minimal efficacy. There are agents in clinical trials investigating novel targeted therapies.

See Clinical trials available at the NCCN member institutions.

Guidelines IndexTh id C i














Thyroid Carcinoma

Follicular Carcinoma


Follicular carcinoma

Total thyroidectomy if invasivecancer, metastatic cancer, or patient decisionIf lymph node(s) positive:

Central neck dissection(level VI)Lateral neck dissection

(levels II–V, sparing spinalaccessory nerve, internal

jugular vein, andsternocleidomastoid muscle)Consider preservation of thecervical sensory nerves,when feasible

·

·

or

Lobectomy/isthmusectomy

PATHOLOGYFINDING


PRIMARY TREATMENT

··

·

·

Chest x-rayConsider lateralneck ultrasound

(category 2B)CT/MRI for fixedor substernallesions (avoidiodinatedcontrast, unlessessential)Evaluate vocalcord mobility(category 2B)

See PostsurgicalEvaluation

(FOLL-2)

Minimallyinvasivecancer a

Follicular adenoma

Invasive cancer (extensivevascular invasion)

Consider completion of thyroidectomy

or

Observe

Observe


aMinimally 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 histologic sections to demonstrate.

See PostsurgicalEvaluation(FOLL-2)

See PostsurgicalEvaluation(FOLL-2)

FOLL-1

Follicular neoplasm

See NoduleEvaluation (THYR-2)

Suppress TSHwith thyroxine

See Surveillanceand Maintenance(FOLL-4)

Guidelines IndexThyroid Carcinoma














No grossresidualdiseasein neck

Grossresidualdiseasein neck


SeeSurveillanceand

Maintenance(FOLL-4)

Unresectable




RT·

·


Total bodyradioiodine scan(category 2B)

FOLL-2

No scanperformed

·

·

·


Post-treatmentI scan

RT

131

Thyroid Carcinoma


Inadequateuptake

Adequateuptake


SeePostsurgicalTherapy(FOLL-3)

·

·

·

·


SeeSurveillanceandMaintenance(FOLL-4)

·

·

·

·


³











Gu de es deThyroid Carcinoma TOC




SeeSurveillanceandMaintenance(FOLL-4)

FOLL-3

Thyroid Carcinoma



RadioiodinemCi

posttreatment scan




stimulation)


b

c


b




b

cSuspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.











in Oncology – v.2.2007Thyroid Carcinoma TOC




Metastatic disease

Surgery (preferred) if resectable

and/or radioiodine treatment,if radioiodine scan positiveand/or RT, if radioiodine scan negative

See Treatment of Metastases (FOLL-5)

RECURRENT DISEASE


d

If there is a high likelihood of therapy, thyroid hormone withdrawal suggested; if not, suggest using rhTSH.

FOLL-4

Thyroid Carcinoma


·

·

·

·



TSH stimulated thyroglobulin withoutradioiodine scan at 12 mo in patients

previously treated with RAI with recentnegative neck ultrasound and undetectableTSH suppressed thyroglobulin (anti-thyroglobulin antibody negative) and T1-2, N0-1, M0 at initial staging

If detectable thyroglobulin, distant metastasesor soft tissue invasion on initial staging,

radioiodine scan every 12 mo until noradioactive iodine avid tumor is evident (either withdrawal of thyroid hormone or rhTSH)d

131³

·

·

·



·

·


Scans (including PET)

negative

/(off


I scan (category 3)

radioiodine

131

®Guidelines IndexThyroid Carcinoma












Solitary CNS

Consider neurosurgical resection

Radioiodine treatment with rhTSH and steroidprophylaxis, if radioiodine scan positive

RT

and/or

and/or

Bone

·

·

·

Surgical palliation, if symptomatic or asymptomaticin weight-bearing extremities

Radioiodine treatment, if radioiodine scan positiveand/or

and/or RTConsider bisphosphonate therapyConsider embolization of metastases


Other extracervical sites

Consider surgical resection of selected, enlarging, or symptomatic metastasesand/or Radioiodine if positive uptake, with consideration of

dosimetry to maximize dosingand/or Clinical trials for non-radioiodine avid tumors;systemic therapy if not in clinical trialor Best Supportive Care

e

FOLL-5

Thyroid Carcinoma


eCytotoxic chemotherapy has shown to have minimal efficacy. There are agents in clinical trials investigating novel targeted therapies.

See Clinical trials available at the NCCN member institutions.


TSH with thyroxine

NCCN®












y

Hürthle Cell Carcinoma


Hürthle cellcarcinoma

Total thyroidectomy, if invasive cancer or patientdecisionIf lymph node(s) positive:

Central neck dissection(level VI)

Consider preservation of thecervical sensory nerves,when feasible

·

· Lateral neck dissection

(levels II–V, sparing spinalaccessory nerve, internal jugular vein, and sterno-cleidomastoid muscle)

or

Lobectomy/isthmusectomy

FNA FINDING DIAGNOSTICPROCEDURES

PRIMARY TREATMENT

·

·

·

·

Chest x-ray

voidiodinated contrastunless essential)Evaluate vocalcord mobility

(category 2B)

Consider lateralneck ultrasound

(category 2B)CT/MRI for fixedor substernallesions (a

Minimallyinvasivecancer a

Hürthleadenoma

Invasive cancer (extensivevascular invasion)

Stronglyconsider completion of thyroidectomy

or

Observe

Observe


Suppress TSHwith thyroxine

See SurveillanceandMaintenance(H RT-4)Ü

See PostsurgicalEvaluation(H RT-2)Ü



aMinimally 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 histologic sections to demonstrate.

H RT-1Ü

H rthleneoplasm

ü See NoduleEvaluation (THYR-2)

NCCN® P ti G id li

Guidelines IndexTh id C i TOC

Thyroid Carcinoma











Gross

residualdiseasein neck


SeeSurveillanceandMaintenance(H RT-4)Ü

Unresectable




·

·

TSH + thyroglobulinmeasurement +antithyroglobulinantibodies (1-12 wkpostoperatively)Total bodyradioiodine scan(category 2B)

H RT-2Ü

RT

No scanperformed

·

·

·


Post-treatmentI scan

RT

131

No grossresidualdiseasein neck

y


Inadequateuptake

Adequateuptake

TSH + thyroglobulinmeasurement +antithyroglobulin

antibodies (1-12 wkpostoperatively)

SeePostsurgicalTherapy(H RT-3)Ü

·

·

·

·


·

·

·

·


³

SeeSurveillanceandMaintenance(H RT-4)Ü

NCCN® Practice G idelines


Thyroid Carcinoma










See

SurveillanceandMaintenance(H RT-4)Ü


T4 (surgicallyevident extra-thyroidalinvasion) andage > 45 y

All others

Consider RT

H RT-3Ü



RadioiodinemCi

posttreatment scan




stimulation)


b

c


b




b

cSuspicion based on pathology, postoperative thyroglobulin, and intraoperative findings.




Thyroid Carcinoma






NCCNPractice Guidelinesin Oncology – v.2.2007

Thyroid Carcinoma TOCStaging, MS, References



Metastatic disease

Surgery (preferred) if resectableand/or

Radioiodine treatment, if radioiodine scan positiveand/or RT, if radioiodine scan negative

See Treatment of Metastases (H RT-5)Ü

RECURRENT DISEASE


d

If there is a high likelihood of therapy, thyroid hormone withdrawal suggested; if not, suggest using rhTSH.

H RT-4Ü


·

·

·

·

·



Periodic neck ultrasound

TSH stimulated thyroglobulin without

radioiodine scan at 12 mo in patientspreviously treated with RAI with recentnegative neck ultrasound and undetectableTSH suppressed thyroglobulin (anti-thyroglobulin antibody negative) and T1-2, N0-1, M0 at initial staging

If detectable thyroglobulin, distant metastases

or soft tissue invasion on initial staging,radioiodine scan every 12 mo until noradioactive iodine avid tumor is evident (either withdrawal of thyroid hormone or rhTSH)d

131³

·

·

·



·

·


Scans (including PET)

negative

/(off


I scan (category 2B)

radioiodine

131



Thyroid Carcinoma










Solitary CNSConsider neurosurgical resection

RTand/or

Bone

·

·

·

Surgical resection, if symptomatic or asymptomatic in weight-bearing extremitiesand/or RTConsider bisphosphonate therapy

Consider embolization of metastases

Other

extracervical sites

Consider surgical resection of selected, enlarging,or symptomatic metastasesand/or Radioiodine if positive uptake, with considerationof dosimetry to maximize dosing

and/or Clinical trials for non-radioiodine avid tumors;systemic therapy if not in clinical trialor Best Supportive Care

e

H RT-5Ü


eCytotoxic chemotherapy has shown to have minimal efficacy. There are agents in clinical trials investigating novel targeted

therapies. See Clinical trials available at the NCCN member institutions.


TSH with thyroxine



Thyroid Carcinoma










y o d Ca c o a OCStaging, MS, ReferencesMedullary Carcinoma


MEDU-1

Medullarythyroidcarcinomaon FNA

···

··

··

·

Calcitonin levelCEAPheochromocytomascreeningSerum calciumScreen for RET proto-oncogene mutations(exons 10, 11, 13-16)

Consider neck ultrasoundEvaluate vocal cordmobility (category 2B)Contrast-enhanced CT of chest and mediastinum

ab

³ 1.0 cm in

diameter or bilateralthyroid disease

< 1.0 cm indiameter andunilateralthyroid disease

·

·

·

Total thyroidectomy withbilateral central (level VI)Consider ipsilateral modifiedradical neck dissection (levels

II–V). Consider contralateralneck dissection if diseasepresent in ipsilateral neck(levels II, III, IV or V)Consider adjuvant RT for T4disease

Total thyroidectomy plusbilateral central neckdissection (level VI)

CLINICALPRESENTATION

ADDITIONAL WORKUP PRIMARY TREATMENT

SeeManagement2-3 MonthsPostoperative

(MEDU-4)

See Additional Workupand Primary Treatment(MEDU-2)

Germline

mutation of RET proto-oncogene

a

bGermline mutation should prompt family testing of first-degree relatives and counseling.

If exons 10, 11, 13-16 negative, evaluate for exon 8.



Thyroid Carcinoma







yStaging, MS, References



ADDITIONAL WORKUP PRIMARY TREATMENT

Germlinemutation of RETproto-oncogene

MEN 2B(codon 883, 918, or 922 RET mutations)

MEN 2Aor Familial medullarythyroid carcinoma(codon 609, 611, 618,620, 630, 634, 768,790, 791, 804 or 891 RET mutations)

cc c c

··

·

Calcitonin levelCEA

Pheochromocytomascreeningd,e

··

····

Basal calcitonin levelCalcium stimulated calcitonin test if calcitoninundetectable (category 2B for use in timing of surgery)CEAPheochromocytoma screeningSerum calciumConsider neck ultrasound (category 2B)

d,e

c

d

e

Lethality of medullary thyroid carcinoma associated with codon 768, 790, 791, and 804 RET mutations may be lower than with other RET mutations. In patients withthese RET mutations, annual provocative (calcium) calcitonin testing may be performed, with total thyroidectomy and central node dissection deferred until testsbecome abnormal after the age of 5. Brandi ML, Gagel RF, Angeli A, et al. Consensus: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J ClinEndocrinol Metab 2002;87(6)5658-71.Evidence of pheochromocytoma should be evaluated and treated appropriately before proceeding to the next step on the pathway.Screening for pheochromocytoma (MEN 2A and 2B) and hyperparathyroidism (MEN 2A) should be performed annually. For some RET mutations (codons 768, 790,

V804M, or 891) less frequent screening may be appropriate.

·

·

·

Total thyroidectomy during the firstyear of life or at diagnosis + bilateralcentral neck dissection (level VI)Consider more extensive nodedissection (levels II–V) if tumor(s)> 0.5 cm in diameter Consider adjuvant RT for T4 disease

See PrimaryTreatment(MEDU-3)

SeeManagement2-3 MonthsPostoperative(MEDU-4)

MEDU-2

Medullary Carcinoma



Thyroid Carcinoma






NCCN in Oncology – v.2.2007 Staging, MS, References


Measureserum intactparathyroidhormone

Notsuppressed

Suppressed

Evaluate for other causesof hyper-calcemia

·

·

·

·

Total thyroidectomy by age 5 or when mutationidentifiedConsider bilateral central neck dissection (levelVI) if elevated calcitonin or CEA test or ultrasound identified thyroid or nodal abnormalityConsider more extensive lymph node dissection(levels II–V) if tumor(s) > 1.0 cm or central node(s)positiveConsider adjuvant RT for T4 disease in adults

c

·

·

·

·

·

Total thyroidectomy by age 5 or when mutationidentifiedConsider bilateral central neck dissection (levelVI) if elevated calcitonin or CEA test or ultrasoundidentified thyroid or nodal abnormalityConsider more extensive lymph node dissection(levels II–V) if tumor(s) > 1.0 cm or central node(s)positiveDuring primary operative procedure andparathyroid exploration:

If single adenoma, exciseIf multiglandular hyperplasia, leave, or autotransplant the equivalent mass of onenormal parathyroidConsider cryopreservation of parathyroid tissue

Consider adjuvant RT for T4 disease in adults

c

?

?

?

MEN 2Aor Familialmedullarythyroidcarcinoma

PRIMARY TREATMENT




MEDU-3

cLethality of medullary thyroid carcinoma associated with codon 768, 790, 791, and 804 RET mutations may be lower than with other RET mutations.In patients with these RET mutations, annual provocative (calcium) calcitonin testing may be performed, with total thyroidectomy and central nodedissection deferred until tests become abnormal after the age of 5. Brandi ML, Gagel RF, Angeli A, et al. Consensus: Guidelines for diagnosis andtherapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2002;87(6)5658-71.

Medullary Carcinoma



Thyroid Carcinoma

M d ll C i








·

·

BasalcalcitoninCEA

Elevatedor

positive

Normalor negative f

·

·

Consider additionalimagingContrast-enhanced CT or

MRI of the neck,chest, abdomenwith liver protocol

MANAGEMENT2-3 MONTHSPOSTOPERATIVE

SURVEILLANCE

Observe

Imagingpositive or symptomaticdisease

Imagingnegative andasymptomatic

See Recurrent or PersistentDisease (MEDU-5)

···

·

·

Annual serum calcitonin, CEAConsider neck ultrasoundAdditional studies or more frequenttesting if significantly risingcalcitonin or CEANo additional imaging required if calcitonin and CEA stable

For MEN 2B or 2A, annualscreenings for pheochromocytomaand hyperparathyroidism(MEN 2A)

Continueobservationor Consider cervicalreoperation, if

primary surgeryincomplete

Continue observation

·

·

·

Annual serumcalcitonin, CEAAdditional studies or more frequent testingif significantly risingcalcitonin or CEANo additional imagingrequired if calcitoninand CEA stable

See Recurrent or Persistent Disease(MEDU-5)

Imagingpositive

Imagingnegative

Imagingpositive

Imagingnegative

f The likelihood of significant residual disease with a negative basal calcitonin is very low.

See Recurrent or

Persistent Disease(MEDU-5)

MEDU-4

Medullary Carcinoma


i O l 2 2007


St i MS R f

Thyroid Carcinoma

M d ll C i








Locoregional

Symptomatic,distant metastases

Asymptomatic,distant metastases

Surgical resection ±postoperative RTor RT, if symptomatic progressivedisease or unresectable

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

Disseminatedsymptomaticdisease

·

·

·

Clinical trial (preferred)or RT for focal symptomsor DTIC-based chemotherapyConsider bisphosphonatetherapy for bone metastasesBest Supportive Care

RECURRENT OR PERSISTENT DISEASE

Observeor Consider resection, if possible,or ablation (eg, RFA,embolization or other regionaltherapy) especially if progressive disease

MEDU-5

Medullary Carcinoma


i O l 2 2007


Staging MS References

Thyroid Carcinoma

Anaplastic Carcinoma






NCCN in Oncology – v.2.2007 Staging, MS, ReferencesAnaplastic Carcinoma


Anaplasticcarcinoma a

FNA OR COREBIOPSY FINDING


PRIMARY TREATMENT

···

·

CBCSerum calciumHead, neck,chest, abdomen,pelvis CTTSH

Locally resectable(rarelyencountered)

Unresectable

local tumor

·

·

Total or near-totalthyroidectomySelective resection of involved local or regionalstructures and lymph nodes

·

·

·

Clinical trials preferredRT (consider hyperfractionation) +chemotherapyBest Supportive Care

ANAP-1

a An FNA diagnosis of anaplastic carcinoma should be confirmed by core biopsy.




http://cancerstaging.net/




http://www.cap.org/apps/docs/cancer_protocols/protocols_index.html




Guidelines Index


Practice Guidelinesin Oncology – v.2.2007 Thyroid Carcinoma

NCCN

®





Version 2.2007, 04/20/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-28

Tumor Size and Recurrence ( )

or Cancer Death ( )

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

Recurrence

R =0.672

Cancer Death

R =0.672

Recurrence ( ) and Cancer Deaths ( )

According to Age at Time of Diagnosis

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.).

Guidelines Index


Practice Guidelinesin Oncology – v.2.2007 Thyroid Carcinoma

NCCN

®





Version 2.2007, 04/20/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-29

Table 2

Mutations of the RET Proto-oncogene Associated with MEN 2 and

Familial Medullary Thyroid Cancer (FMTC)

Affected Clinical Percentage of All

Codon/Exon Syndrome(s) MEN 2 Mutations

609/10 MEN 2A, FMTC 0 - 1%

611/10 MEN 2A, FMTC 2 - 3%

618/10 MEN 2A, FMTC 3 - 5%

620/10 MEN 2A, FMTC 6 - 8%

630/11 MEN 2A, FMTC 0 - 1%

634/11 MEN 2A 80-90%

635/11 MEN 2A Rare

637/11 MEN 2A Rare768/13 FMTC Rare

790/13 MEN 2A, FMTC Rare

791/13 FMTC Rare

804/13 MEN 2A, FMTC 0 - 1%

883/15 MEN 2B Rare

891/15 FMTC Rare

918/16 MEN 2B 3 - 5%922/16 MEN 2B Rare

With permission, from the , Volume

62:377-411 ©2000 by Annual Reviews

Annual Review of Physiology

www.AnnualReviews.org

http://www.annualreviews.org/

http://www.annualreviews.org/




http://seer.cancer.gov/csr/1975_2001/


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