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NCCN Guidelines IndexThyroid Table of Contents
Discussion
NCCN.org
Continue
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) ®
Thyroid CarcinomaVersion 2.2012
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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
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
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P i t d b E V l ti 5/21/2012 12 02 03 PM F l l N t d f di t ib ti C i ht © 2012 N ti l C h i C N t k I All Ri ht R d
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NCCN Guidelines IndexThyroid Table of Contents
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
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NCCN Guidelines IndexThyroid Table of Contents
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-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
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NCCN Guidelines IndexThyroid Table of Contents
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.
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
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NCCN Guidelines IndexThyroid Table of Contents
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.
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)
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Papillary Carcinoma
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
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Papillary Carcinoma
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.
See Principles of TSH Suppression (THYR-A).
Total body
radioiodine imaging(category 2B) withadequate TSHstimulation (thyroidwithdrawal or recombinant humanTSH (rhTSH)stimulation)or
Clinical indicationfor radioiodinetherapy(category 2B)
i Suppress TSHwithlevothyroxine g
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Papillary Carcinoma
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.
.
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NCCN Guidelines IndexThyroid Table of Contents
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)
Completion of thyroidectomy
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
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.
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.
See Principles of TSH Suppression (THYR-A).
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
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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
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Follicular Carcinoma
FOLL-3
Suppress TSHwithlevothyroxine e
SeeSurveillanceandMaintenance(FOLL-4)
RadioiodinemCi
post-treatment imagingor consider dosimetryfor distant metastasis
treatment(100-200 ) andi
POSTSURGICAL THERAPY
2-12 wkpost-thyroidectomy:No gross residualdisease in neck withadequate TSHstimulation(thyroid withdrawalor rhTSH stimulation)
Suspected or proven radioiodineresponsiveresidual tumor
f
h
Suspected or proven thyroidbed uptake
f
No radioiodinetreatment
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.
See Principles of TSH Suppression (THYR-A).
Tg < 1 ng/mL withnegativeantithyroglobulinantibodies andradioiodineimaging negative
Consider adjuvantradioiodine ablation(30-100 mCi)
and post-treatmentimaging
i todestroy residualthyroid function
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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
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Follicular Carcinoma
FOLL-5
TREATMENT OF METASTASES
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)
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 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 Principles of TSH Suppression (THYR-A)
See Clinical trials available at the NCCN member institutions.
.
Metastatic diseaseContinue to suppress
TSH with levothyroxinee
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NCCN Guidelines IndexThyroid Table of Contents
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.
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
DIAGNOSTICPROCEDURES
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)
Completion of thyroidectomy
or
Observe
Observe
Completion of thyroidectomy
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
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – H rthle Cell Carcinomaü
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.
See Principles of TSH Suppression (THYR-A).
Consider radioiodine (RAI)therapy based on clinicalindications for RAIh,i
Not considering RAI therapybecause of lack of clinicalindication for RAIh,i
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – H rthle Cell Carcinomaü
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
POSTSURGICAL THERAPY
2-12 wk post-thyroidectomy:No gross residualdisease in neckwith adequate TSHstimulation (thyroidwithdrawal or rhTSH stimulation)
Suspected or proven radioiodineresponsiveresidual tumor
h
j
Suspected or proven thyroidbed uptake
h
No radioiodinetreatment
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.
See Principles of TSH Suppression (THYR-A).
Tg < 1 ng/mLwith negativeantithyroglobulinantibodies andradioiodineimaging negative
Consider adjuvantradioiodine ablation(30-100 mCi)
and post-treatment
imaging
k todestroy residualthyroid function
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NCCN G id li V i 2 2012
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – H rthle Cell Carcinomaü
H RT-5Ü
TREATMENT OF METASTASES
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
Sites other than CNS
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 Principles of TSH Suppression (THYR-A)
See Clinical trials available at the NCCN member institutions
.
.
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NCCN G id li I dNCCN G id li V i 2 2012
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NCCN Guidelines IndexThyroid Table of Contents
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.
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)
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NCCN Guidelines IndexNCCN Guidelines Version 2 2012
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Medullary Carcinoma
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
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NCCN Guidelines IndexThyroid Table of Contents
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Medullary Carcinoma
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
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Thyroid Table of ContentsDiscussion
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.
NCCN Guidelines Version 2.2012Thyroid Carcinoma – Anaplastic Carcinoma
ANAP-1
Anaplasticcarcinomaa
FNA OR COREBIOPSY FINDING
DIAGNOSTICPROCEDURES
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
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NCCN Guidelines Indexf C
NCCN Guidelines Version 2.2012 Staging
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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
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NCCN Guidelines IndexThyroid Table of Contents
Discussion
NCCN Guidelines Version 2.2012Thyroid Carcinoma
A ti t ith l ti th id h d d bl l t
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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.
NCCN Guidelines IndexThyroid Table of Contents
Discussion
NCCN Guidelines Version 2.2012Thyroid Carcinoma
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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.).
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